Development of Personalized Strategies for Precisely Battling Malignant Melanoma.

Melanoma is the most severe and fatal form of skin cancer, resulting from multiple gene mutations with high intra-tumor and inter-tumor molecular heterogeneity. Treatment options for patients whose disease has progressed beyond the ability for surgical resection rely on currently accepted standard therapies, notably immune checkpoint inhibitors and targeted therapies. Acquired resistance to these therapies and treatment-associated toxicity necessitate exploring novel strategies, especially those that can be personalized for specific patients and/or populations. Here, we review the current landscape and progress of standard therapies and explore what personalized oncology techniques may entail in the scope of melanoma. Our purpose is to provide an up-to-date summary of the tools at our disposal that work to circumvent the common barriers faced when battling melanoma.

Clinical Features of Pingueculitis Revealed by Anterior Segment Optical Coherence Tomography Findings.

PURPOSE: To investigate clinical features and treatment outcomes of pingueculitis with morphological assessments using anterior segment optical coherence tomography (AS-OCT). METHODS: In this retrospective observational study, we examined 22 eyes of 22 patients with pingueculitis. All patients were treated with the same 2-week course of prednisolone acetate 1% drops four times per day. The clinical parameters evaluated were surface dimensions determined by slitlamp biomicroscopy, cross-sectional dimensions determined by AS-OCT, and symptom scores determined by patient surveys. Pretreatment and 1-month posttreatment values were compared with Wilcoxon signed-rank tests. Patients were followed up to 1 year after treatment. RESULTS: Twenty-two eyes from 22 patients (4 men and 18 women) with an average age of 37.7±8.8 (range, 27-57) years and an average duration of symptoms of 22 (range, 5-60) days were included. The average follow-up period was 14.7±0.8 (range, 12-22) months. Mean pretreatment horizontal length, vertical length, conjunctival thickness, and cross-sectional area were 2.4±0.69 mm, 2.0±0.6 mm, 1.82±0.60 µm, and 5.14±2.05 mm, respectively. Mean posttreatment horizontal length, vertical length, conjunctival thickness, and area were 1.93±0.5 mm, 1.52±0.6 mm, 1.03±0.46 µm, and 2.33±0.83 mm, respectively. Mean pretreatment and posttreatment dry eye symptom scores were 3.27±0.77 and 1.13±0.38, respectively. The median pretreatment and posttreatment changes were statistically significant by Wilcoxon signed-rank tests for horizontal length (P<0.001), vertical length (P<0.001), conjunctival thickness (P=0.003), cross-sectional area (P=0.003), and dry eye symptom scores (P<0.001). CONCLUSION: Anterior segment optical coherence tomography allows the quantification of differences in the pingueculitis measurements before and after treatment. In this retrospective study, a short course of topical steroids effectively treated the inflammation in a sustained manner. Anterior segment optical coherence tomography demonstrated significant reduction in the thickness and cross-sectional area of the pinguecula and a conversion back to a homogeneous conjunctival stroma.

Optimal size of pterygium excision for limbal conjunctival autograft using fibrin glue in primary pterygia.

BACKGROUND: In our study we describe a method that optimizes size of excision and autografting for primary pterygia along with the use of intraoperative MMC and fibrin glue. Our objective is to propose a simple, optimizedpterygium surgical technique with excellent aesthetic outcomes and low rates of recurrence and otheradverse events. METHODS: Retrospective chart review of 78 consecutive patients with stage III primary pterygia who underwent an optimal excision technique by three experienced surgeons. The technique consisted of removal of the pterygium head, excision of the pterygium body and Tenon's layer limited in proportion to the length of the head, application of intraoperative mitomycin C to the defect, harvest of superior bulbar limbal conjunctival graft, adherence of graft with fibrin glue. Outcomes included operative time, follow up period, pterygium recurrence, occurrences of incorrectly sized grafts, and other complications. RESULTS: All patients were followed up for more than a year. Of the 78 patients, there were 2 cases of pterygium recurrence (2.6%). There was one case of wound dehiscence secondary to small-sized donor conjunctivaand one case of over-sized donor conjunctiva, neither of which required surgical correction. There were no toxic complications associated with the use of mitomycin C. CONCLUSION: Correlating the excision of the pterygium body and underlying Tenon's layer to the length of the pterygium head, along with the use intraoperative mitomycin C, limbal conjunctival autografting, and fibrin adhesionresulted in excellent outcomes with a low rate of recurrence for primary pterygia.

Novel limbal dermoid surgery for visual acuity and cosmesis improvement: A 7-year retrospective review.

BACKGROUND: To report a long-term outcome of the novel combined surgical method of complete excision, corneal tattooing, and a sutureless limbal conjunctival autograft for limbal dermoid. METHODS: All patients who were referred to our clinic for limbal dermoid, and underwent a combined surgery of complete excision, corneal tattooing, and a sutureless limbal conjunctival autograft were retrospectively reviewed. The surgery was performed by one surgeon, and all clinical information was obtained during a seven-year follow up period. In all patients, surgical outcomes of cosmesis, best corrected visual acuity (BCVA), spherical equivalent (SE), and corneal/ocular astigmatism were obtained and compared preoperatively and postoperatively. RESULTS: During seven years, 24 patients (24 eyes) with limbal dermoid were finally enrolled. The mean age was 10.1±8.9 years old. The surgery resulted in an improved appearing ocular surface in all cases without any complications. There was no statistical difference in BCVA, corneal and ocular astigmatism between preoperatively and postoperatively (p = 0.231, 0.156 and 0.475, respectively). The mean SE was 0.12±3.19D preoperatively, and -0.21±3.02 D postoperatively with statistical significance (p = 0.037). Mean follow up period was 54.50 ± 15.62 months. CONCLUSIONS: Based on the results of this study, our innovative surgical method which includes complete excision with corneal tattooing and limbal conjunctival autograft can be a simple and safe procedure that achieves long standing cosmesis with limbal dermoids.

Ez-Metastasizing: The Crucial Roles of Ezrin in Metastasis.

Ezrin is the cytoskeletal organizer and functions in the modulation of membrane-cytoskeleton interaction, maintenance of cell shape and structure, and regulation of cell-cell adhesion and movement, as well as cell survival. Ezrin plays a critical role in regulating tumor metastasis through interaction with other binding proteins. Notably, Ezrin has been reported to interact with immune cells, allowing tumor cells to escape immune attack in metastasis. Here, we review the main functions of Ezrin, the mechanisms through which it acts, its role in tumor metastasis, and its potential as a therapeutic target.

Effect of Head Trauma-Related Deaths on Corneal Endothelial Cell Loss in Eye Bank Donors.

PURPOSE: The purpose of this study was to examine the effect of head trauma-related deaths on corneal endothelial cell density (ECD) in eye bank donors. METHODS: This is a retrospective study of 287 corneas from donors with causes of death secondary to motor vehicle accident with sustained head trauma (n = 50), gunshot wound to the head (n = 138), fall with sustained head trauma (n = 2), and non-head-related traumatic causes of death (n = 97). Donors older than age 50 years were excluded due to concern for undiagnosed Fuchs endothelial dystrophy as a potential confounder for the cause of endothelial cell loss. Donor characteristics, ECD, and focal endothelial cell loss on specular microscopy were compared between the groups. Donors in the head trauma and nonhead trauma groups were matched by age; there were 42 age-matched donors in both groups. RESULTS: Age and ECD were negatively correlated (Pearson correlation coefficient = -0.57). Death-to-preservation time was not significantly different between the 2 groups ( P value = 0.59). The mean ECD in the head trauma group was 2859 ± 370 cells/mm 2 and 3041 ± 464 cells/mm 2 in the nonhead trauma group. The head trauma group had a lower ECD (178 ± 70 cells/mm 2 , P value = 0.013). After matching for age, the difference in ECD between the 2 groups was -94 ± 82 cells/mm 2 ( P value = 0.26). The adjusted odds of having focal endothelial cell loss was not statistically significant ( P value = 0.50) between the groups. CONCLUSIONS: After statistical adjustments, there were no differences between the head trauma and nonhead trauma groups.

A case of sight threatening complications from topical 1% 5-fluorouracil in the treatment of ocular surface squamous neoplasia.

PURPOSE: 1% topical 5-fluorouracil (5-FU) is a treatment for ocular surface squamous neoplasia (OSSN) due to its effectiveness, low cost, and tolerable side effect profile. To our knowledge there is no reported sight-threatening corneal complication of 1% 5-FU for the treatment of OSSN. OBSERVATIONS: We report a 78 year-old man with bilateral conjunctival intraepithelial neoplasia (CIN) who developed bilateral corneoscleral ulceration and corneal perforation of the left eye after 1% 5-FU topical treatment. CONCLUSIONS AND IMPORTANCE: Our case report describes serious potential complications of 1% 5-FU, reviews possible risk factors associated with poor outcomes, and discusses our treatment approach.

Expanding Understanding of Thyroid Eye Disease Manifestations to Include Hispanic and Black Patients.

PURPOSE: Knowledge of thyroid eye disease (TED) is based on predominantly Caucasian populations. To date, no studies in the United States examine the presentation in Black and Hispanic patients. The purpose of this study is to introduce the presentation of TED in two previously undescribed populations. METHODS: This is a retrospective, cross-sectional, chart review study of patients with TED at a tertiary center using the Strengthening the Reporting of Observational Studies in Epidemiology checklist. The main outcome measure for severity was the European Group on Graves' Orbitopathy 2016 Severity Scale. RESULTS: Of the 2905 charts reviewed, 99 met the inclusion criteria. The mean age was 51 (standard deviation 16) years with 78% women. Race was 49.4% Black, 39.1% Hispanic, 9.2% Caucasian, and 2.3% Asian. Smoking rates were 25% current smokers and 14% former smokers. Manifestations were proptosis (94% Hispanic and 91% Black), eyelid retraction (85% Hispanic and 79% Black), extraocular muscle (EOM) restriction (79% Hispanic and 63% Black), eyelid edema (41% Hispanic and 30% Black), chemosis (24% Hispanic and 14% Black), and optic neuropathy (18% Hispanic and 9% Black). Overall, disease severity was 22% mild, 65% moderate to severe, and 13% sight-threatening. Older patients had increased rates of optic neuropathy (P = 0.04). Younger patients had increased rates of proptosis (P = 0.02). Socioeconomic status was not associated with disease severity (P = 0.67). CONCLUSION: Hispanic and Black patients with TED presented with higher than previously established rates of proptosis, EOM restriction, and optic neuropathy. Including research of different races broadens understanding of presentation and management, improving patient outcomes.

The Improvement of Dry Eye Symptoms after Pinguecula Excision and Conjunctival Autograft with Fibrin Glue.

PURPOSE: To evaluate the association between pinguecula excision and subsequent improvement in dry eye syndrome. METHODS: We included 30 consecutive patients with primary nasal pinguecula and dry eye symptoms undergoing ocular surgery for the first time. Criteria for pinguecula excision surgery were nasal location, yellowish color, and protrusion of conjunctiva at least 2 times thicker than adjacent normal conjunctiva as measured by anterior segment optical coherence tomography. Our primary outcomes were 3-month postoperative changes in tear film breakup time (TBUT), Schirmer test, and a dry eye symptom score. RESULTS: 30 eyes from 30 different patients (12 men and 18 women) underwent pinguecula excision and conjunctival autografting using fibrin glue. The mean age was 42.5 ± 8.35 (range 28-63) years. The preoperative protrusion ratio of pinguecula was 2.33 ± 0.28 (range 2.00-2.90). Mean preoperative TBUT, Schirmer test, and dry eye symptom scores were 5.10 ± 1.27 seconds, 6.07 ± 2.27 mm, and 2.80 ± 0.76 points. Mean postoperative 3-month TBUT, Schirmer test, and dry eye symptom scores were 7.80 ± 1.13 seconds, 7.27 ± 2.02 mm, and 0.30 ± 0.47 points, respectively. The median pre- and postoperative changes were found to be statistically significant by Wilcoxon signed-rank tests for TBUT, Schirmer test score, and dry eye symptom score. CONCLUSION: Surgical excision of pinguecula and conjunctival autograft using fibrin glue is an effective and safe method to improve symptoms of dry eye syndrome.

Donor Diabetes Mellitus Severity and Corneal Transplant Suitability in a US Eye Bank Donor Population.

PURPOSE: To determine whether donor diabetes mellitus (DM) severity is associated with differences in endothelial cell density (ECD) and surgically unsuitable tissue. METHODS: Raw data were obtained from Saving Sight Eye Bank (Kansas City, MO) including 10,454 donated eyes from 5346 eligible donors from July 2014 through May 2017. Donors were grouped into 5 categories by their insulin use and the presence of microvascular end-organ complications. The categories were non-DM (NDM), noninsulin-dependent DM without complications (NIDDMnc), noninsulin-dependent DM with complication (NIDDMc), insulin-dependent DM without complications, and insulin-dependent DM with complication. Outcome variables included ECD and tissue transplant suitability. Mixed effects models were used to adjust for the random effect of repeated measures and fixed effects of donor age, race, lens status, and death to refrigeration and death to preservation times. Interaction effects of DM severity group and donor age and DM severity group and lens status were included in the models. RESULTS: One thousand six hundred eighty-four (32.1%) donors had a diagnosis of DM. Six hundred fifty-eight donors were in the NIDDMnc group, 225 in the NIDDMc group, 404 in the insulin-dependent DM without complication group, and 397 in the insulin-dependent DM with complication group. Compared with non-DM, donors with DM were older (P < 0.001) and more likely to be pseudophakic (P < 0.001). DM severity groups did not affect adjusted ECD at mean donor age. There was no statistically significant ECD interaction between DM severity group and lens status. There was a statistically significant ECD crossover interaction with NIDDMnc and donor age (P < 0.001). In phakic eyes, NIDDMc was associated with a statistically significantly lower odds of transplant suitability (odds ratio 0.62, P = 0.006). CONCLUSIONS: DM severity does not affect lowering adjusted ECD at mean donor age. DM severity and pseudophakia were not associated with lower adjusted ECD. NIDDMnc was associated with an attenuation of the age-dependent decrease in ECD. NIDDMc was associated with decreased transplant suitability in phakic eyes. Future studies should include age, lens status, and interaction effects in their models of ECD and transplant suitability.

Technician Consistency in Specular Microscopy Measurements: A "Real-World" Retrospective Analysis of a United States Eye Bank.

PURPOSE: To quantify consistency of endothelial cell density (ECD) measurements among technicians in a single US eye bank operating under typical operating conditions. METHODS: In this retrospective analysis of 51 microscopy technicians using a semiautomated counting method on 35,067 eyes from July 2007 to May 2015, technician- and date-related marginal ECD effects were calculated using linear regression models. ECD variance was correlated with the number of specular microscopy technicians. RESULTS: Technician mean ECDs ranged from 2386 ± 431 to 3005 ± 560 cells/mm. Nine technicians had statistically and clinically significant marginal effects. Annual mean ECDs adjusted for changes in technicians ranged from 2422 ± 433 to 2644 ± 430 cells/mm. The period of 2007 to 2009 had statistically and clinically significant marginal effects. There was a nonstatistically significant association between the number of technicians and ECD standard deviation. CONCLUSIONS: There was significant ECD variability associated with specular microscopy technicians and with the date of measurement. We recommend that eye banks collect data related to laboratory factors that have been shown to influence ECD variability.

Association Between Corneal Endothelial Cell Density and Topical Glaucoma Medication Use in an Eye Bank Donor Population.

PURPOSE: To evaluate the association between corneal endothelial cell density (ECD) and donor topical glaucoma medication use in an eye bank database. METHODS: Raw eye bank data included 19,159 donors over the period July 2007 to May 2015. Free-text, donor medication lists were retrospectively searched for glaucoma medication. Exclusion criteria were age less than 40 years, history of eye surgery, endothelial trauma, guttae, and cell densities <1000 or >3300/mm. Analysis of covariance was used to test differences in cell density between groups while adjusting for age. Linear regression was used to test the correlation of independent interval variables while adjusting for age. RESULTS: Twelve thousand one hundred fifty-seven donors were included in the final analysis; 134 were on topical glaucoma medication. The mean ECD for donors not on glaucoma medication and pooled donors on glaucoma medication was 2561 ± 348 and 2516 ± 320 cells/mm, respectively (P = 0.42). Subgroup analysis by medication class resulted in nonstatistically significant differences between ECDs of nonmedicated donors and donors on alpha agonists (P = 0.76), beta blockers (P = 0.90), carbonic anhydrase inhibitors (P = 0.13), cholinergics (P = 0.37), and prostaglandin analogs (P = 0.62). The number of glaucoma medication classes used by donors was not a statistically significant predictor of endothelial density (P = 0.298). CONCLUSIONS: Donors on topical glaucoma medication do not have ECDs statistically significantly lower than donors not on medication.