An intraocular solitary fibrous tumor/hemangiopericytoma with extrascleral extension: Case report and review of literature.

Purpose: To report a case of intraocular solitary fibrous tumor/hemangiopericytoma (SFT/HPC) complicated by extrascleral extension and to review the current literature regarding intraocular SFT/HPC. Observations: A twenty-two year old male presented with decreased vision in his left eye and was found to have a subretinal mass with extrascleral extension. He underwent enucleation of his left eye and histopathology confirmed a diagnosis of SFT/HPC. Conclusions and importance: To our knowledge, this is the seventh case of intraocular SFT/HPC ever reported and the first to report extrascleral extension. At the time of publication, there was no evidence of metastases. Extensive clinical, ophthalmic and radiographic imaging, and histopathologic data are presented to contribute to the current understanding of intraocular SFT/HPC.

Von Hippel-Lindau Syndrome Phenotype With Prominent Vitreoretinal Neovascularization Treated With Early PPV: A Case Series and Literature Review.

BACKGROUND AND OBJECTIVE: To describe a case series of three patients in one family with Von Hippel-Lindau (VHL) disease who presented with vitreoretinal neovascularization and resulting tractional retinal detachments (TRDs). This vitreoretinal phenotype of VHL may benefit from early surgical intervention. PATIENTS AND METHODS: Descriptive case series of three patients in one family with VHL disease. A review of the literature regarding surgical intervention for VHL was performed. RESULTS: All three patients developed prominent intravitreal neovascularization with fibrovascular growth within the vitreous secondary to a retinal capillary hemangioma. Two subjects with intravitreal neovascularization were treated with laser and cryotherapy but eventually developed a TRD. The final vision in these two patients was light perception and 20/300. The eye that was preemptively treated with vitrectomy to remove the vitreous sustaining the neovascularization had visual acuity of 20/50 after surgery. CONCLUSION: Intravitreal neovascularization with fibrovascular proliferation may be an indication for vitrectomy prior to the development of retinal detachment. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:109-115.].

Surgical timing and presence of a vitreoretinal fellow on postoperative adverse events following pars plana vitrectomy.

INTRODUCTION: To evaluate the adverse event rate following pars plana vitrectomy as a function of surgical start time and the presence of a vitreoretinal fellow. METHODS: Single-institution retrospective cohort study of patients undergoing pars plana vitrectomy from 1 January 2016 to 31 December 2016 at Stanford University School of Medicine (Palo Alto, CA, USA). Records were reviewed for surgical start time, the presence of vitreoretinal fellow, and postoperative adverse events defined as any finding deviating from the expected postoperative course requiring observation or intervention. RESULTS: A total of 310 pars plana vitrectomies were performed. There was no statistical difference in the rate of any adverse event when comparing cases starting after 16:01 (9/13, 69.2%) and after 12:01 (42/99, 42.4%) to a morning start time (69/198, 34.9%, adjusted p = 0.083). There was a statistically significant increase in the risk of postoperative vitreous hemorrhage with afternoon and evening cases as compared to morning cases (adjusted p = 0.021). In addition, there was no difference in any adverse event with a fellow present (93/244, 38.1%) compared to without (27/66, 40.9%, adjusted p = 0.163). There was a higher risk of postoperative hypotony when a fellow was involved (6.6% vs 0%, p = 0.028), though this difference disappeared after adjusting for confounders (adjusted p = 0.252). There was no difference in the length of surgery with and without a fellow (49 vs 54 min, respectively; p = 0.990). DISCUSSION: Afternoon start time and the presence of a fellow were not independent risk factors for postoperative adverse events.

Postoperative Adverse Events, Interventions, and the Utility of Routine Follow-Up After 23-, 25-, and 27-Gauge Pars Plana Vitrectomy.

PURPOSE: To evaluate the utility of standard postoperative visit (POV) intervals in pars plana vitrectomy (PPV) as a function of adverse events (AEs) identified. DESIGN: Retrospective case review. METHODS: The medical records of all patients undergoing 23-, 25-, and 27-gauge PPV from January 1, 2016 to December 31, 2016 were reviewed. Each POV was assessed as a standard (s-POV), physicianadjusted (a-POV), or patient-initiated visit (p-POV). Preoperative features, diagnoses, and surgical procedures were evaluated to determine protective and risk factors for AEs. RESULTS: A total of 256 patients (310 PPVs) were included in this study. The most common cumulative postoperative AEs were elevated intraocular pressure (>30 mm Hg) (12.3%), cystoid macular edema (6.1%), and retinal detachment (5.8%). Patients with the diagnosis of macular hole or epiretinal membrane had the lowest relative risk of AEs [0.30; 95% confidence interval (CI), 0.12-0.75 and 0.36; 95% CI, 0.21-0.63, respectively]. There was no difference in time to AE among different vitrectomy gauge sizes (P = 0.733). Patients in a-POV and p-POV groups had a statistically significant higher incidence of AEs in the POV day 5-10 window (P = 0.004). CONCLUSIONS: The utility of standard POVs in detecting AEs is dependent on the indication for PPV. Specifically patients undergoing isolated macular surgery (epiretinal membrane peel or macular hole repair) had the lowest relative risk of postoperative AEs and may warrant a less-intensive follow-up regimen.

Outer Retinal Defects Represent a Normal Recovery Pathway Following Internal Limiting Membrane Peeling in Macular Hole Surgery.

BACKGROUND AND OBJECTIVE: To examine perioperative factors associated with the development of outer retinal defects (ORDs) following surgical repair of macular holes (MHs). PATIENTS AND METHODS: An institutional review board-approved, retrospective, interventional cohort study was conducted. Patients who underwent MH repair during a 5-year period were identified. Statistical analysis was conducted to detect significant perioperative associations to ORD development. RESULTS: One hundred twenty-four eyes were included, and 54% developed an ORD following surgery. These defects correlated with lower preoperative stage (P = .0057), preoperative phakia (P = .036), and lack of prior macular surgery (P = .0016). Patients in the ORD group had significantly better preoperative and postoperative visual acuity (P = .031 and P = .0004, respectively), but there was no difference in change in acuity from preoperatively to 3 months postoperatively when compared with control patients (P = 42). The majority (89%) of ORDs resolved by 24 months postoperatively. CONCLUSION: The development of ORDs appears to be correlated with several factors indicative of favorable overall eye health and less advanced pathology and may represent a normal state of recovery after MH repair with internal limiting membrane peeling. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e1-e8.].

Orbital, eyelid, and nasopharyngeal silicone oil granuloma presenting as ptosis & pseudo-xanthelasma.

PURPOSE: To highlight the presentation and management of a patient with eyelid, orbital and nasopharyngeal silicone oil migration through a glaucoma drainage implant presenting as pseudo-xanthelasma and ptosis. OBSERVATIONS: A 68-year male presented with unilateral ptosis and presumed xanthelasma. He had a history of glaucoma drainage implant surgery, pseudophakia, and multiple retinal detachment repairs with silicone oil. During ptosis repair it was discovered that his presumed xanthelasma was in fact an eyelid silicone granuloma. Additional work up revealed silicone infiltration of the eyelids, orbits, and nasopharynx, resulting from emulsified silicone oil leakage through his glaucoma valve implant. CONCLUSIONS AND IMPORTANCE: Silicone oil may emulsify with time, with potential egress via a glaucoma filtration device. Clinicians should be alert for eyelid, orbital and sinonasal findings that may indicate occult migration.

A novel classification of high myopia into anterior and posterior pathologic subtypes.

PURPOSE: High myopia and pathologic myopia are common causes of visual morbidity. Myopic pathology can affect all regions of the retina, though there is currently no classification system to distinguish anterior (peripheral) and posterior (macular) pathology. We hypothesize that these classifications are characterized by distinct demographic and refractive features, highlighting the disparity in types of pathologic myopia. METHODS: Institutional retrospective cohort study. The Stanford University Medical Center Clinical Data Warehouse was used to identify patients with high myopia by ICD-9 and ICD-10 codes. Predetermined ICD diagnoses were then used to classify patients with high myopia into isolated high myopia (IHM), anterior pathologic myopia (APM), posterior pathologic myopia (PPM), and combined pathologic myopia (CPM). A cohort of this population was then manually reviewed to gather refractive data and confirm accuracy of ICD coding. RESULTS: Patients (3274) were identified with high myopia. Overall, 22.1% individuals met criteria for APM, 10.7% for PPM, 17.0% for CPM, and 50.2% for IHM. We identified a significantly higher frequency of females with PPM compared to APM (62.3 vs. 48.3%; OR, 1.73; 95% CI, 1.34 to 2.25), Asian patients with PPM as compared to APM (42.9 vs. 33.3%; OR, 1.50; 95% CI, 1.16 to 1.95), and younger patients with APM compared to PPM (median 45.3 vs. 63.4 years). The refractive error was significantly more myopic in the CPM (median - 9.8D; interquartile range, IQR 6.7) and PPM (median - 10.5D; IQR 9.8) subgroups as compared to the APM (median - 8.1D; IQR 3.5), and IHM (median - 8.2D; IQR 4.1) subgroups (p = 0.003). CONCLUSIONS: High myopia may be divided into four distinct subgroups based on presence and location of pathology, which is associated with differences in age, gender, race, and refractive error.

Spontaneous Globe Rupture Due to Rapidly Evolving Endogenous Hypermucoid Klebsiella Pneumoniae Endophthalmitis.

In this retrospective report, the authors describe a rare case of spontaneous globe rupture from Klebsiella pneumoniae endophthalmitis in a middle-aged man with poorly controlled type 2 diabetes mellitus. There have been only four previously reported cases of spontaneous globe rupture from endophthalmitis. Out of the now five reported cases, all have been due to endogenous endophthalmitis, four have been due to gram-negative bacteria, and three have been due to K. pneumoniae. K. pneumoniae, especially the hypermucoid variant with a protective polysaccharide capsule, is an emerging pathogen with remarkable virulence. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:600-601.].

New device for creating a continuous curvilinear capsulorhexis.

PURPOSE: To describe the evolution of a new device to facilitate continuous curvilinear capsulorhexis (CCC) creation. SETTING: Department of Ophthalmology, University of Colorado School of Medicine, Aurora, Colorado, USA. DESIGN: Experimental study. METHODS: Bench-side ex vivo testing of unique prototypes for guidance and assistance of CCC in bovine and human eyes was performed. Five designs were sequentially tested as follows: a flexible circular blade of nickel-titanium alloy (nitinol), a flexible nitinol guide wire, a flexible elastomeric suction device, a combination approach of a nitinol guide wire and flexible silicone ring, and a freestanding micropatterned silicone ring. RESULTS: The first 3 designs were not amenable to insertion through a sub-2.4 mm corneal incision and failed to maintain adequate downward force to cut the capsule and/or prevent radial tears. The fourth design was successfully inserted through a 2.4 mm incision and maintained adequate downward pressure and contact to guide a manual CCC without radial tears. The final design was insertable through a 2.4 mm incision and exhibited self-adhesive characteristics after placement on the anterior capsule of an ophthalmic viscosurgical device-filled anterior chamber. CONCLUSIONS: Given the steep learning curve of manual capsulorhexis and the high cost of capsulotomy-assistive devices, such as the femtosecond laser, an alternative approach for creating a CCC is desirable. Performance of a highly precise manual CCC through a small incision using a medical-grade silicone device with an adhesive micropatterned design is a viable and cost-effective option for use in cataract surgery across a wide range of user experience. FINANCIAL DISCLOSURE: All authors are named as the inventors in a patent filed by the University of Colorado covering the details in this report.

Enhanced arginine methylation of programmed cell death 4 protein during nutrient deprivation promotes tumor cell viability.

The role of programmed cell death 4 (PDCD4) in tumor biology is context-dependent. PDCD4 is described as a tumor suppressor, but its coexpression with protein arginine methyltransferase 5 (PRMT5) promotes accelerated tumor growth. Here, we report that PDCD4 is methylated during nutrient deprivation. Methylation occurs because of increased stability of PDCD4 protein as well as increased activity of PRMT5 toward PDCD4. During nutrient deprivation, levels of methylated PDCD4 promote cell viability, which is dependent on an enhanced interaction with eIF4A. Upon recovery from nutrient deprivation, levels of methylated PDCD4 are regulated by phosphorylation, which controls both the localization and stability of methylated PDCD4. This study reveals that, in response to particular environmental cues, the role of PDCD4 is up-regulated and is advantageous for cell viability. These findings suggest that the methylated form of PDCD4 promotes tumor viability during nutrient deprivation, ultimately allowing the tumor to grow more aggressively.

Therapeutic potential of the anti-diabetic agent metformin in targeting the skin cancer stem cell diaspora.

Type II diabetes is associated with increased prevalence of cancer including both melanoma and squamous cell carcinoma (SCC) of the skin. Emerging evidence from epidemiological studies suggest that diabetic patients on metformin have a lower risk of cancer incidence and mortality in a broad range of neoplasms. In both melanoma and SCC, populations of cancer stem cells (CSC) contribute to tumor initiation and metastasis. We propose that metformin constitutes a new class of targeted therapy that acts on the skin CSC diaspora. We posit that metformin selectively and simultaneously targets CSCs of the primary tumor as well as in metastatic niches thereby disrupting the dynamic dispersal of circulating CSCs between the primary tumor and metastatic site. This hypothesis suggests a new concept in dermato-oncology that treatment of type II diabetes and prevention of skin cancer are two sides of the same coin.

Sedation-related outcomes in postoperative management of pediatric laryngotracheal reconstruction.

OBJECTIVE: Examine outcomes of varied postoperative sedation management in pediatric patients recovering from single stage laryngotracheal reconstruction. DESIGN: Retrospective review of 34 patients treated with single stage laryngotracheal reconstruction from 2001 through 2011. SETTING: Tertiary children's hospital. METHODS: Patients were divided into 2 groups: those managed postoperatively with sedation, with or without paralysis (group 1), and those managed awake with narcotic pain medication as needed for primary management (group 2). Outcomes were measured as a function of sedation management. Outcomes investigated focused on those related to the success of the airway reconstruction, and those related to sedation management. RESULTS: Out of 68 cases of laryngotracheal reconstruction reviewed from 2001 to 2011, 34 were single stage reconstructions. Nineteen patients were sedated postoperatively (group 1) and fifteen patients were left awake (group 2). There were no significant differences between groups in airway-related outcomes, including risk of accidental decannulation, revision rates, and need for secondary airway procedures such as balloon dilation. Sedation-related outcomes, specifically focusing on differences in medical management, showed significant increases in rates of withdrawal (p<0.0001), nursing concerns of withdrawal (p<0.0001) and sedation level (p<0.0001), pulmonary complications (OR 7.7, p=0.008), and prolonged hospital stay due to withdrawal (p=0.0005) in patients managed with sedation with or without paralysis. Multivariable regression analysis revealed that duration of sedation was the primary risk factor for increased postoperative morbidity, while younger age, lower weight, and use of a posterior graft were also significant variables assessed. CONCLUSION: Avoiding sedation as the standard for postoperative management of single stage laryngotracheal reconstruction airway patients leads to an overall decreased risk of morbidity without increasing risk of airway-specific morbidity. This is specifically as related to withdrawal, pulmonary complications, concerns about sedation level and prolonged hospital course, all of which increase significantly with increased level and duration of sedation.

Protein arginine methyltransferase 5 accelerates tumor growth by arginine methylation of the tumor suppressor programmed cell death 4.

Programmed cell death 4 (PDCD4) has been described as a tumor suppressor, with high expression correlating with better outcomes in a number of cancer types. Yet a substantial number of cancer patients with high PDCD4 in tumors have poor survival, suggesting that oncogenic pathways may inhibit or change PDCD4 function. Here, we explore the significance of PDCD4 in breast cancer and identify protein arginine methyltransferase 5 (PRMT5) as a cofactor that radically alters PDCD4 function. Specifically, we find that coexpression of PDCD4 and PRMT5 in an orthotopic model of breast cancer causes accelerated tumor growth and that this growth phenotype is dependent on both the catalytic activity of PRMT5 and a site of methylation within the N-terminal region of PDCD4. In agreement with the xenograft model, elevated PDCD4 expression was found to correlate with worse outcome within the cohort of breast cancer patients whose tumors contain higher levels of PRMT5. These results reveal a new cofactor for PDCD4 that alters its tumor suppressor functions and point to the utility of PDCD4/PRMT5 status as both a prognostic biomarker and a potential target for chemotherapy.

Systemic overexpression of IL-10 induces CD4+CD25+ cell populations in vivo and ameliorates type 1 diabetes in nonobese diabetic mice in a dose-dependent fashion.

Early systemic treatment of nonobese diabetic mice with high doses of recombinant adeno-associated virus (rAAV) vector expressing murine IL-10 prevents type 1 diabetes. To determine the therapeutic parameters and immunological mechanisms underlying this observation, female nonobese diabetic mice at 4, 8, and 12 wk of age were given a single i.m. injection of rAAV-murine IL-10 (10(4), 10(6), 10(8), and 10(9) infectious units (IU)), rAAV-vector expressing truncated murine IL-10 fragment (10(9) IU), or saline. Transduction with rAAV-IL-10 at 10(9) IU completely prevented diabetes in all animals injected at all time points, including, surprisingly, 12-wk-old animals. Treatment with 10(8) IU provided no protection in the 12-wk-old injected mice, partial prevention in 8-wk-old mice, and full protection in all animals injected at 4 wk of age. All other treatment groups developed diabetes at a similar rate. The rAAV-IL-10 therapy attenuated pancreatic insulitis, decreased MHC II expression on CD11b+ cells, increased the population of CD11b+ cells, and modulated insulin autoantibody production. Interestingly, rAAV-IL-10 therapy dramatically increased the percentage of CD4+CD25+ regulatory T cells. Adoptive transfer studies suggest that rAAV-IL-10 treatment alters the capacity of splenocytes to impart type 1 diabetes in recipient animals. This study indicates the potential for immunomodulatory gene therapy to prevent autoimmune diseases, including type 1 diabetes, and implicates IL-10 as a molecule capable of increasing the percentages of regulatory cells in vivo.