Global Tracheostomy Collaborative: data-driven improvements in patient safety through multidisciplinary teamwork, standardisation, education, and patient partnership.

There is growing recognition of the need for a coordinated, systematic approach to caring for patients with a tracheostomy. Tracheostomy-related adverse events remain a pervasive global problem, accounting for half of all airway-related deaths and hypoxic brain damage in critical care units. The Global Tracheostomy Collaborative (GTC) was formed in 2012 to improve patient safety and quality of care, emphasising knowledge, skills, teamwork, and patient-centred approaches. Inspired by quality improvement leads in Australia, the UK, and the USA, the GTC implements and disseminates best practices across hospitals and healthcare trusts. Its database collects patient-level information on quality, safety, and organisational efficiencies. The GTC provides an organising structure for quality improvement efforts, promoting safety of paediatric and adult patients. Successful implementation requires instituting key drivers for change that include effective training for health professionals; multidisciplinary team collaboration; engagement and involvement of patients, their families, and carers; and data collection that allows tracking of outcomes. We report the history of the collaborative, its database infrastructure and analytics, and patient outcomes from more than 6500 patients globally. We characterise this patient population for the first time at such scale, reporting predictors of adverse events, mortality, and length of stay indexed to patient characteristics, co-morbidities, risk factors, and context. In one example, the database allowed identification of a previously unrecognised association between bleeding and mortality, reflecting ability to uncover latent risks and promote safety. The GTC provides the foundation for future risk-adjusted benchmarking and a learning community that drives ongoing quality improvement efforts worldwide.

Predicting the content of anthraquinone bioactive in Rhei rhizome (Rheum officinale Baill.) with the concentration addition model.

Rhei rhizome (Rheum officinale Baill.) (RR) contains a large number of anthraquinone bioactive, yet little is known of the combined effect of these anthraquinones in a mixture. The goals of this study were: to determine the inhibitory potencies of individual anthraquinones and whole RR extract against human liver microsomal CYP1A2/3A4 activity, to predict the content of anthraquinones in RR using the concentration addition (CA) model, and to compare predicted and empirical contents in the same RR sample. Anthraquinone concentrations in the RR extract were determined using HPLC. The inhibitory potencies of individual anthraquinones were determined in incubations containing human liver microsomes. The study results were used to predict an effect-based dose measure of the anthraquinones in RR using the CA model. An empirical dose measure also was determined in the whole RR extract using the CYP1A2/3A4-based bioassay. For the CYP1A2-based studies, the predicted and empirical dose measures of anthraquinones were identical; they were 12.0 ±â€¯1.80 and 12.20 ±â€¯0.81 mg aloe-emodin equivalents/g RR, respectively. For the CYP3A4-based studies, the predicted and empirical dose measures were different; they were 2.80 ±â€¯0.10 and 19.04 ±â€¯0.41 mg aloe-emodin equivalents/g RR, respectively. Only the CYP1A2-based CA model which assumed additive effects of RR anthraquinones predicted an effect-based dose measure that was verifiable by empirical data. The CA model provides an alternative approach to the CYP1A2/3A4-based bioassay or empirical method to screen for the anthraquinones in RR. The CA model as described in this study is applicable to other botanical drugs, plant-based foods and dietary supplements.

Omalizumab facilitates rapid oral desensitization for peanut allergy.

BACKGROUND: Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions. OBJECTIVE: We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients. METHODS: Thirty-seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. RESULTS: The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab-treated subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo (P < .01). Twenty-three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000-mg food challenge. Overall reaction rates were not significantly lower in omalizumab-treated versus placebo-treated subjects (odds ratio, 0.57; P = .15), although omalizumab-treated subjects were exposed to much higher peanut doses. CONCLUSION: Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach.

Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration.

Despite significant progress in the identification of genetic loci for age-related macular degeneration (AMD), not all of the heritability has been explained. To identify variants which contribute to the remaining genetic susceptibility, we performed the largest meta-analysis of genome-wide association studies to date for advanced AMD. We imputed 6 036 699 single-nucleotide polymorphisms with the 1000 Genomes Project reference genotypes on 2594 cases and 4134 controls with follow-up replication of top signals in 5640 cases and 52 174 controls. We identified two new common susceptibility alleles, rs1999930 on 6q21-q22.3 near FRK/COL10A1 [odds ratio (OR) 0.87; P = 1.1 × 10(-8)] and rs4711751 on 6p12 near VEGFA (OR 1.15; P = 8.7 × 10(-9)). In addition to the two novel loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB (rs641153), C3 (rs2230199), C2 (rs9332739), CFI (rs10033900), LIPC (rs10468017), TIMP3 (rs9621532) and CETP (rs3764261) were confirmed with genome-wide significant signals in this large study. Loci in the recently reported genes ABCA1 and COL8A1 were also detected with suggestive evidence of association with advanced AMD. The novel variants identified in this study suggest that angiogenesis (VEGFA) and extracellular collagen matrix (FRK/COL10A1) pathways contribute to the development of advanced AMD.

Infected epithelial inclusion cyst simulating conjunctival melanoma.

There are several pigmented nonneoplastic lesions that can clinically simulate melanocytic tumors. The authors report an unusual conjunctival epithelial inclusion cyst that contained luminal bacterial colonies, hemorrhage, and epithelial debris. Clinical appearance convincingly simulated a melanoma. The clinical and histopathologic features of this lesion are discussed.

Early anti-VEGF treatment for radiation maculopathy and optic neuropathy: lessons learned.

Radiation therapy has saved both sight and life for eye cancer patients. The most common methods include ophthalmic plaque brachytherapy and external beam techniques. However, subsequent dose-dependent radiation vasculopathy invariably occurs within and around the targeted zone. In 2006, Finger discovered that periodic intravitreal anti-vascular endothelial growth factor (anti-VEGF) bevacizumab could reverse and suppress intraocular radiation vasculopathy. At first, it was administered at the onset of radiation-related vision loss. Though bevacizumab induced regression of macular oedema, retinal haemorrhages and cotton-wool infarcts, most patients were left with residual retinal damage, manifest as metamorphopsia and loss of vision. These results led to earlier and earlier anti-VEGF interventions: first after signs of progressive radiation retinopathy, and then for signs of radiation maculopathy, and finally for high-risk eyes with no clinical signs of retinopathy. Earlier initiation of intravitreal anti-VEGF therapy typically resulted in greater restoration and preservation of macular anatomy, reductions of retinal haemorrhages, resolution of cotton-wool spots and vision preservation. Recent research on optical coherence tomography angiography (OCT-A) has revealed that radiation vasculopathy occurs prior to clinical ophthalmic signs or symptoms. Therefore, it seemed reasonable to consider treating high-risk patients (considered certain to eventually develop radiation maculopathy) to prevent or delay vision loss. Herein, we describe the evolution of treatment for radiation maculopathy as well as recent research supporting anti-VEGF treatment of high-risk patients immediately following radiation to maximize vision outcomes.

First clinical implementation of Yttrium-90 Disc Brachytherapy after FDA clearance.

PURPOSE: Herein, we study if high-dose-rate (HDR) yttrium-90 (90Y) brachytherapy could be utilized by medical physicists, radiation oncologists, and ophthalmic surgeons. METHODS AND MATERIALS: Yttrium-90 (90Y) beta-emitting brachytherapy sources received United States Food and Drug Administration clearance for episcleral treatment of ocular tumors and benign growths. Dose calibration traceable to the National Institute of Standards and Technology as well as treatment planning and target delineation methods were established. Single-use systems included a 90Y-disc affixed within specialized, multifunction, handheld applicator. Low-dose-rate to high-dose-rate prescription conversions and depth-dose determinations were performed. Radiation safety was evaluated based on live exposure rates during assembly and surgeries. Clinical data for radiation safety, treatment tolerability, and local control was collected. RESULTS: Practice parameters for the medical physicist, radiation oncologist, and ophthalmic surgeon were defined. Device sterilizations, calibrations, assemblies, surgical methods, and disposals were reproducible and effective. Treated tumors included iris melanoma, iridociliary melanoma, choroidal melanoma, and a locally invasive squamous carcinoma. Mean calculated 90Y disc activity was 14.33 mCi (range 8.8-16.6), prescription dose 27.8 Gy (range 22-30), delivered to depth of 2.3 mm (range 1.6-2.6), at treatment durations of 420 s (7.0 min, range 219 s-773 s). Both insertion and removal were performed during one surgical session. After surgery, each disc-applicator- system was contained for decay in storage. Treatments were well-tolerated. CONCLUSIONS: HDR 90Y episcleral brachytherapy devices were created, implementation methods developed, and treatments performed on 6 patients. Treatments were single-surgery, rapid, and well-tolerated with short-term follow up.

A five-year study of slotted eye plaque radiation therapy for choroidal melanoma: near, touching, or surrounding the optic nerve.

OBJECTIVE: To evaluate slotted eye plaque radiation therapy for choroidal melanomas near the optic disc. DESIGN: A clinical case series. PARTICIPANTS: Twenty-four consecutive patients with uveal melanomas that were near, touching, or surrounding the optic disc. INTERVENTION: Slotted eye plaque radiation therapy. MAIN OUTCOME MEASURES: Recorded characteristics were related to patient, clinical, and ophthalmic imaging. Data included change in visual acuity, tumor size, recurrence, eye retention, and metastasis. RESULTS: From 2005 to 2010, 24 consecutive patients were treated with custom-sized plaques with 8-mm-wide, variable-depth slots. Radiation doses ranged from 69.3 to 163.8 Gy (mean, 85.0 Gy) based on delivering a minimum tumor dose of 85 Gy. All treatments were continuously delivered over 5 to 7 days. Mean patient age at presentation was 57 years. Tumors were within 1.5 mm of the optic nerve (n = 3, 13%), juxtapapillary (n = 6, 25%), touching ≥180 degrees (n = 7, 29%), or circumpapillary (n = 8, 33%). Ultrasound revealed dome-shaped tumors in 79% of patients, collar-button tumors in 17% of patients, irregular tumor in 1 patient (4%), and intraneural invasion in 2 patients. Mean initial largest basal dimension was 11.0 mm (standard deviation [SD] ± 3.5 mm; median, 11.4 mm; range, 5.9-16.4 mm). Mean initial tumor thickness was 3.5 mm (SD ± 1.7 mm; median, 3.0 mm; range, 1.4-6.9 mm). Initial visual acuities were a median 20/25 (range, 20/20 to hand motions) and decreased to a median 20/40 (range, 20/20 to no light perception). At a mean follow-up of 23 months, 12 patients required periodic intravitreal bevacizumab to suppress radiation optic neuropathy (RON) or maculopathy. To date, there has been a 100% local control rate. No patients have required secondary enucleation for recurrence or neovascular glaucoma. No patients have developed metastasis. CONCLUSIONS: Slotted plaque radiation therapy allows peripapillary, juxtapapilary, and circumpapillary choroidal melanomas (and a safety margin) to be included in the radiation targeted zone. Normalization of the plaque position beneath the tumor appears to increase RON and improve local control.

Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes.

PURPOSE: To investigate whether the 2 subtypes of advanced age-related macular degeneration (AMD), choroidal neovascularization (CNV), and geographic atrophy (GA) segregate separately in families and to identify which genetic variants are associated with these 2 subtypes. DESIGN: Sibling correlation study and genome-wide association study (GWAS). PARTICIPANTS: For the sibling correlation study, 209 sibling pairs with advanced AMD were included. For the GWAS, 2594 participants with advanced AMD subtypes and 4134 controls were included. Replication cohorts included 5383 advanced AMD participants and 15 240 controls. METHODS: Participants had the AMD grade assigned based on fundus photography, examination, or both. To determine heritability of advanced AMD subtypes, a sibling correlation study was performed. For the GWAS, genome-wide genotyping was conducted and 6 036 699 single nucleotide polymorphisms (SNPs) were imputed. Then, the SNPs were analyzed with a generalized linear model controlling for genotyping platform and genetic ancestry. The most significant associations were evaluated in independent cohorts. MAIN OUTCOME MEASURES: Concordance of advanced AMD subtypes in sibling pairs and associations between SNPs with GA and CNV advanced AMD subtypes. RESULTS: The difference between the observed and expected proportion of siblings concordant for the same subtype of advanced AMD was different to a statistically significant degree (P = 4.2 × 10(-5)), meaning that in siblings of probands with CNV or GA, the same advanced subtype is more likely to develop. In the analysis comparing participants with CNV to those with GA, a statistically significant association was observed at the ARMS2/HTRA1 locus (rs10490924; odds ratio [OR], 1.47; P = 4.3 × 10(-9)), which was confirmed in the replication samples (OR, 1.38; P = 7.4 × 10(-14) for combined discovery and replication analysis). CONCLUSIONS: Whether CNV versus GA develops in a patient with AMD is determined in part by genetic variation. In this large GWAS meta-analysis and replication analysis, the ARMS2/HTRA1 locus confers increased risk for both advanced AMD subtypes, but imparts greater risk for CNV than for GA. This locus explains a small proportion of the excess sibling correlation for advanced AMD subtype. Other loci were detected with suggestive associations that differ for advanced AMD subtypes and deserve follow-up in additional studies.

Refractory squamous cell carcinoma of the conjunctiva treated with subconjunctival ranibizumab (Lucentis): a two-year study.

PURPOSE: To test the safety, tolerability, and efficacy of subconjunctival ranibizumab (Lucentis [Genentech, Inc.]) for squamous cell carcinoma of the conjunctiva and cornea. METHODS: Five patients with recurrent squamous cell carcinoma of the conjunctiva and cornea enrolled in this nonrandomized, single center, phase I pilot study as an alternative to radiation or exenteration. Subconjunctival ranibizumab (0.5 mg) was given on a monthly or twice monthly basis. Patients were examined for safety, tolerability, and efficacy using visual acuity, blood pressure, urinalysis, comparative slit lamp biomicroscopy with photography, and high frequency ultrasound imaging. RESULTS: Five male patients with biopsy-proven squamous conjunctival carcinoma were found to have recurrent disease. Each patient had been initially treated with combinations of primary excision (n = 1) or excision and cryotherapy (n = 4), and all (n = 5) had failed separate courses of both topical interferon a and mitomycin 0.02%. Tumors were multifocal and involved between 8 and 12 clock hours of the limbus. A median of 22 injections (range 12-27) was given over a mean 19 months (range 6-24). Three patients had a complete response (no clinically apparent disease) during the 2-year study, while 2 failed treatment despite demonstrating an initial partial response. Treatment was well-tolerated, as 4 patients demonstrated stable or improved visual acuity, and none had significant systemic or ocular side effects. CONCLUSIONS: This 2-year study demonstrated that subconjunctival ranibizumab induced regression of squamous cell carcinoma of the conjunctiva and cornea. Therefore, antivascular endothelial growth factor chemotherapy may offer a new strategy, complement excision and cryotherapy, or provide an alternative to radiation and/or exenteration. Further, larger investigations utilizing a larger group of patients are needed to determine the ideal dose, route of drug delivery, and case selection.

Patients presenting with metastases: stage IV uveal melanoma, an international study.

OBJECTIVE: To analyse ocular and systemic findings of patients presenting with systemic metastasis. METHODS AND ANALYSIS: It is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases. RESULTS: Of 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1-T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category. CONCLUSIONS: Though higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.

Palladium-103 plaque therapy for multifocal iris melanoma: Radiation of the entire anterior segment of the eye.

PURPOSE: To investigate the safety and tolerability of total anterior segment palladium-103 (103Pd) eye plaque brachytherapy for multifocal iris melanoma. METHODS: Interventional case series of 11 patients with multifocal iris melanomas. Anterior segment ultrasound revealed tumor size, location, and intraocular margins. Epicorneal amniotic membrane grafts protected the cornea and decreased pain during total anterior segment 103-Pd ophthalmic plaque brachytherapy. RESULTS: Eleven diffuse iris melanomas were American Joint Committee on Cancer 8th edition-classified as T1 (n = 5, 45.5%) and T2 (n = 6, 54.5%). Plaque radiation was completed to a minimum mean tumor dose of 85 Gy (mean dose rate, 58.1 cGy/h). Ultrasonographic tumor thickness regression was 41% (follow up mean 58.7, median 50, range: 8-139 months). Despite 100% local control and 100% eye retention, one patient (9.1%) developed metastatic disease. Four eyes required cataract surgery. There was no corneal stem-cell deficiency, corneal opacity, radiation maculopathy, or optic neuropathy. While visual acuity prior to treatment was 20/40 or better in 10 (91%), 9 were 20/40 or better (81.9%) at last follow-up. Four (36%) had glaucoma prior to treatment and three eyes developed glaucoma after treatment for a total of 63%. CONCLUSION: Total anterior segment (103Pd) plaque brachytherapy resulted in local control, good visual acuity, eye and life preservation in the treatment of multifocal iris melanoma.

Hypochlorous acid antiseptic washout improves patient comfort after intravitreal injection: A patient reported outcomes study.

PURPOSE: Current ocular antiseptic practice for intravitreal injection (IVI) employs 5% povidone-iodine (Betadine®) drops which frequently cause ocular discomfort and prolonged irritation. In an effort to improve comfort while maintaining efficacy, we studied a hypochlorous acid (HOCL 0.01%) spray washout prior to injection. METHODS: Patients had received a minimum of 3 IVIs prepared with Betadine®antisepsis prior to entry in this study. Their subsequent IVIs were prepared with Betadine®followed by HOCL 0.01% washout. Facets of comfort were measured by a Likert-scaled questionnaire to compare their experiences after IVI. RESULTS: Thirty-seven participants were enrolled. Addition of HOCL 0.01% spray after Betadine®reduced the duration of discomfort (P = 0.001) and need for artificial tears postinjection (P = 0.003). It improved their reported quality of life (P = 0.04) and sleep (P = 0.01). There were neither HOCL-related side effects nor endophthalmitis during this study. CONCLUSION: Topical HOCL 0.01% spray after topical Betadine®antisepsis significantly improved patient comfort following IVIs.

Palladium-103 ophthalmic plaque radiation therapy for choroidal melanoma: 400 treated patients.

PURPOSE: To describe 18 years of experience with palladium-103 ((103)Pd) ophthalmic plaque brachytherapy. DESIGN: Retrospective case series. PARTICIPANTS: From 1990 to 2007, 400 patients were diagnosed with uveal melanoma, found negative for metastatic disease, and treated. Episcleral (103)Pd radiation was delivered to a mean apical radiation dose of 73.3 Gy over 5 to 7 continuous days. INTERVENTION: Palladium-103 ophthalmic plaque brachytherapy. MAIN OUTCOME MEASURES: Patients were evaluated for local tumor control, visual acuity, radiation damage (retinopathy, optic neuropathy, cataract), and metastatic disease. RESULTS: A total of 272 tumors (68%) were located at or posterior to the equator. There were 186 (46.5%) T1 tumors, 156 (39%) T2 tumors, 50 (12.5%) T3 tumors, and 8 (2%) T4 tumors. Patients were followed for a maximum of 205 months (mean, 51.1 months). Fourteen patients required secondary enucleation (5 for tumor growth and 9 for glaucoma pain control). The local control rate was 96.7%. Life table analysis of patients with 20/200 or better before treatment (n = 357) suggests that 79% and 69% are expected to retain that acuity for 5 and 10 years, respectively. Life table analysis demonstrates a probability that 92.7% and 86.6% of patients will be free of metastatic disease at 5 and 10 years, respectively. CONCLUSIONS: In a nonrandomized phase I clinical evaluation, (103)Pd ophthalmic plaque radiotherapy was used to treat 400 patients with uveal melanoma. In this series, results after (103)Pd ophthalmic plaque radiotherapy were superior to those reported for alternative forms of radiation.

Reactive keratoma of the central corneal epithelium.

PURPOSE: The authors present a unique corneal tumor. METHODS: A 75-year-old gardener presented with a 1-year history of a slowly growing central corneal lesion with progressive visual loss. We performed an ophthalmic examination, slit lamp photography, high-frequency ultrasonography, and culture with sensitivity (followed by therapeutic scrape biopsy). RESULTS: Clinical examination revealed a gray-white central corneal tumor without extension to the limbus. No significant tumor neovascularization or intraocular inflammation was noted. High frequency ultrasound revealed no penetration of the corneal stroma. The tumor was removed with a platinum spatula. Histopathology revealed simple hyperkeratosis characterized by stratified hyperkeratotic corneal epithelium with metaplastic granular layer characteristic of epidermis. Few and focal clusters of passenger bacteria were found (as seen in cutaneous leukoplakia). Cultures revealed a few Gram-positive cocci and no fungus. A human papilloma virus wide-screen spectrum assay (in situ hybridization) was negative. CONCLUSIONS: The authors present a benign keratoma of the central corneal epithelium. High frequency ultrasound and scrape biopsy histopathologic techniques were used to diagnose and treat this keratoleukoma caused by a reactive keratoma as well as improve his vision.

Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome.

Relatively little is known about the genetic aberrations of conjunctival melanomas (CoM) and their correlation with clinical and histomorphological features as well as prognosis. The aim of this large collaborative multicenter study was to determine potential key biomarkers for metastatic risk and any druggable targets for high metastatic risk CoM. Using Affymetrix single nucleotide polymorphism genotyping arrays on 59 CoM, we detected frequent amplifications on chromosome (chr) 6p and deletions on 7q, and characterized mutation-specific copy number alterations. Deletions on chr 10q11.21-26.2, a region harboring the tumor suppressor genes, PDCD4, SUFU, NEURL1, PTEN, RASSF4, DMBT1, and C10orf90 and C10orf99, significantly correlated with metastasis (Fisher's exact, p ≤ 0.04), lymphatic invasion (Fisher's exact, p ≤ 0.02), increasing tumor thickness (Mann-Whitney, p ≤ 0.02), and BRAF mutation (Fisher's exact, p ≤ 0.05). This enhanced insight into CoM biology is a step toward identifying patients at risk of metastasis and potential therapeutic targets for systemic disease.

Topical interferon alfa in the treatment of conjunctival melanoma and primary acquired melanosis complex.

PURPOSE: To report on topical interferon alfa-2b for conjunctival malignant melanoma (CMM) and primary acquired melanosis with atypia (PAM). DESIGN: Retrospective, interventional case series. METHODS: Five eyes of five consecutive patients with biopsy-proven malignant melanoma were treated with topical interferon alfa-2b as treatment for primary or recurrent disease. One drop of interferon alfa-2b (1 million units/ml) was placed into the superior fornix four times daily for three months. Punctal plugs limited systemic absorption. The main outcome measure was tumor regression by clinical examination and comparative slit-lamp photography. RESULTS: Five consecutive patients with conjunctival melanoma (American Joint Committee on Cancer-International Union Against Cancer stages T2 [n = 3] and T3 [n = 2]) were included. Two patients had recurrent corneal tumors, eight and 13 months after local excision, cryotherapy, and topical mitomycin C therapy. Two months after topical interferon alfa-2b treatment, the lesions regressed without side effects. Two additional patients (who could not tolerate topical mitomycin C) were switched to topical interferon alfa-2b. They experienced transient chemical conjunctivitis and have no signs of recurrence (mean, 15 months of follow-up). The fifth had recurrent tumor despite multiple surgeries. This melanoma did not respond to topical interferon alfa-2b nor did the patient tolerate treatment (keratoconjunctivitis). No systemic side effects were noted. CONCLUSIONS: We present evidence that conjunctival and corneal melanoma regresses after exposure to topical interferon alfa-2b. A larger-scale longer-term study must evaluate the long-term efficacy and safety of this therapy.

Anti-vascular endothelial growth factor bevacizumab (avastin) for radiation retinopathy.

OBJECTIVE: To evaluate intravitreal bevacizumab for radiation retinopathy. METHODS: After plaque radiation therapy, 6 patients developed radiation retinopathy (retinal edema, hemorrhages, microangiopathy, and neovascularization). Intravitreal bevacizumab (1.25 mg in 0.05 mL) was periodically injected (every 6-8 weeks). Ophthalmic evaluations included visual acuity, ophthalmic examination, fundus photography, fluorescein angiography, and optical coherence tomography/scanning laser ophthalmoscopy (OCT/SLO) imaging. RESULTS: No bevacizumab-related ocular or systemic adverse effects have occurred within the first 8 months of therapy. Progressive reductions in retinal hemorrhages, exudates, cotton-wool spots, and microangiopathy were documented by photography, angiography, and OCT/SLO imaging. Decreased macular edema was the most common finding. Improvement or stabilization of visual acuity was noted in all cases. CONCLUSIONS: Intravitreal bevacizumab was tolerated, improved or maintained vision, and reduced hemorrhage and retinal edema (angiographic leakage). This study should lead to additional and longer-term studies of humanized monoclonal anti-vascular endothelial growth factor antibody therapy for radiation retinopathy.

High-frequency ultrasound characteristics of 24 iris and iridociliary melanomas: before and after plaque brachytherapy.

OBJECTIVE: To evaluate size, characteristics, and regression of iris and iridociliary melanomas on high-frequency ultrasound images before and after plaque brachytherapy. METHODS: Retrospective review of high-frequency ultrasound characteristics of 24 consecutive iris and iridociliary melanomas before and after radiation therapy. RESULTS: The median tumor thickness before radiation therapy was 2.3 mm (range, 1.4-4.3 mm). Nineteen iris melanomas (79%) involved the ciliary body, 18 (75%) involved the iris pigment epithelium, 11 (46%) were club shaped, and 4 (17%) caused disinsertion of the iris root. At a median follow-up of 30 months after plaque brachytherapy, the mean tumor thickness had diminished to 1.2 mm (median, 1.2 mm; range, 0.9-1.9 mm). While all tumors exhibited a reduction in thickness, no tumors showed additional regression after 30 months past treatment. Fourteen tumors (58%) were noted to have increases in internal reflectivity. There was 1 failure of local control (at 6 years), successfully treated by a second application of plaque brachytherapy. CONCLUSION: High-frequency ultrasonography revealed unique tumor characteristics, quantified tumor size, and demonstrated tumor response to radiation therapy.