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Paschalis EI, Eliott D, Vavvas DG. Removal of Silicone Oil From Intraocular Lens Using Novel Surgical Materials. Transl Vis Sci Technol 2014;3(5):4.Abstract

PURPOSE: To design, fabricate, and evaluate novel materials to remove silicone oil (SiO) droplets from intraocular lenses (IOL) during vitreoretinal surgery. METHODS: Three different designs were fabricated using soft lithography of polydimethylsiloxane (PDMS), three-dimensional (3D) inverse PDMS fabrication using water dissolvable particles, and atomic layer deposition (ALD) of alumina (Al2O3) on surgical cellulose fibers. Laboratory tests included static and dynamic contact angle (CA) measurements with water and SiO, nondestructive x-ray microcomputer tomography (micro-CT), and microscopy. SiO removal was performed in vitro and ex vivo using implantable IOLs and explanted porcine eyes. RESULTS: All designs exhibited enhanced hydrophobicity and oleophilicity. Static CA measurements with water ranged from 131° to 160° and with SiO CA approximately 0° in 120 seconds following exposure. Nondestructive x-ray analysis of the 3D PDMS showed presence of interconnected polydispersed porosity of 100 to 300 μm in diameter. SiO removal from IOLs was achieved in vitro and ex vivo using standard 20-G vitrectomy instrumentation. CONCLUSION: Removal of SiO from IOLs can be achieved using materials with lower surface energy than that of the IOLs. This can be achieved using appropriate surface chemistry and surface topography. Three designs, with enhanced hydrophobic properties, were fabricated and tested in vitro and ex vivo. All materials remove SiO within an aqueous environment. Preliminary ex vivo results were very promising, opening new possibilities for SiO removal in vitreoretinal surgeries. TRANSLATIONAL RELEVANCE: This is the first report of an instrument that can lead to successful removal of SiO from the surface of IOL. In addition to the use of this instrument/material in medicine it can also be used in the industry, for example, retrieval of oil spills from bodies of water.

Omoto M, Katikireddy KR, Rezazadeh A, Dohlman TH, Chauhan S. Mesenchymal stem cells home to inflamed ocular surface and suppress allosensitization in corneal transplantation. Invest Ophthalmol Vis Sci 2014;Abstract

Purpose: To investigate whether systemically-injected syngeneic mesenchymal stem cells (MSCs) can home to the inflamed transplanted cornea, suppress induction of alloimmunity, and promote allograft survival. Methods: MSCs were generated from bone marrow of wild-type BALB/c or GFP+ C57BL/6 mice, and 1x106 cells were intravenously injected to allografted recipients 3 hours after surgery. MSCs homing to the cornea were examined at day 3 post-transplantation by immunohistochemistry. CD11c+MHC II+ cells were detected in the cornea and lymph nodes (LNs) 14 days post-transplantation using flow cytometry. Cytokine expression of bone marrow-derived dendritic cells (BMDCs) was determined using real-time PCR. ELISPOT assay was used to assess indirect and direct host T cell allosensitization, and graft survival was evaluated by slit-lamp biomicroscopy weekly up to 8 weeks. Results: Intravenously injected GFP+ MSCs were found in abundance in the transplanted cornea, conjunctiva, and lymph nodes, but not in the ungrafted (contralateral) tissue. The frequencies of mature CD11c+MHC II+ APCs were substantially decreased in the corneas and draining LNs of MSC-injected allograft recipients compared to control recipients. Maturation and function of in vitro cultured BMDCs was decreased when cocultured with MSCs. Draining LNs of MSC-injected allograft recipients showed significantly lower frequencies of IFNγ-secreting Th1 cells compared to the control group. Allograft survival rate was significantly higher in MSC-injected recipients compared to non-MSC injected recipients. Conclusions: Our data demonstrate that systemically-administered MSCs specifically home to transplanted corneas and promote allograft survival by inhibiting APC maturation and induction of alloreactive T cells.

Ghafouri RH, Allard FD, Migliori ME, Freitag SK. Lower Eyelid Involutional Ectropion Repair With Lateral Tarsal Strip and Internal Retractor Reattachment With Full-Thickness Eyelid Sutures. Ophthal Plast Reconstr Surg 2014;30(5):424-426.Abstract

PURPOSE: To report a novel surgical technique for lower eyelid involutional ectropion repair using a lateral tarsal strip and internal retractor reattachment procedure involving full-thickness eyelid sutures. METHODS:: A retrospective review was performed of patients who underwent repair of involutional ectropion via lateral tarsal strip and internal retractor reattachment with full-thickness eyelid sutures by 1 surgeon. Patients having concomitant or previous eyelid surgical procedures were excluded. Collected data included patient demographics, surgical outcomes, and length of follow up. RESULTS:: Forty-one lower eyelids of 31 patients with involutional ectropion underwent surgical repair. There were 17 men and 14 women in the age range of 69 to 92 years (mean age 82.2 ± 5.9 years). Surgical sites included 22 right and 19 left lower eyelids. Follow up ranged from 1 to 48 months with an average of 5.9 months. Surgical success with anatomical correction of involutional ectropion was achieved in 39 of 41 eyelids (95.1%). There were no perioperative or postoperative complications. Two of 41 (4.9%) eyelids had recurrence of ectropion 7 and 18 months after the procedure. CONCLUSIONS:: This procedure combining lateral tarsal strip with internal retractor reattachment involving full-thickness eyelid sutures effectively addresses horizontal eyelid laxity and tarsal instability, providing an effective technique to correct involutional ectropion of the lower eyelid.

Pasquale LR, Jiwani AZ, Zehavi-Dorin T, Majd A, Rhee DJ, Chen T, Turalba A, Shen L, Brauner S, Grosskreutz C, Gardiner M, Chen S, Borboli-Gerogiannis S, Greenstein SH, Chang K, Ritch R, Loomis S, Kang JH, Wiggs JL, Levkovitch-Verbin H. Solar exposure and residential geographic history in relation to exfoliation syndrome in the United States and Israel. JAMA Ophthalmol 2014;132(12):1439-45.Abstract
IMPORTANCE: Residential (geographic) history and extent of solar exposure may be important risk factors for exfoliation syndrome (XFS) but, to our knowledge, detailed lifetime solar exposure has not been previously evaluated in XFS. OBJECTIVE: To assess the relation between residential history, solar exposure, and XFS. DESIGN, SETTING, AND PARTICIPANTS: This clinic-based case-control study was conducted in the United States and Israel. It involved XFS cases and control individuals (all ≥60-year-old white individuals) enrolled from 2010 to 2012 (United States: 118 cases and 106 control participants; Israel: 67 cases and 72 control participants). MAIN OUTCOMES AND MEASURES: Weighted lifetime average latitude of residence and average number of hours per week spent outdoors as determined by validated questionnaires. RESULTS: In multivariable analyses, each degree of weighted lifetime average residential latitude away from the equator was associated with 11% increased odds of XFS (pooled odds ratio [OR], 1.11; 95% CI, 1.05-1.17; P < .001). Furthermore, every hour per week spent outdoors during the summer, averaged over a lifetime, was associated with 4% increased odds of XFS (pooled OR, 1.04; 95% CI, 1.00-1.07; P = .03). For every 1% of average lifetime summer time between 10 am and 4 pm that sunglasses were worn, the odds of XFS decreased by 2% (OR, 0.98; 95% CI, 0.97-0.99; P < .001) in the United States but not in Israel (OR, 1.00; 95% CI, 0.99-1.01; P = .92; P for heterogeneity = .005). In the United States, after controlling for important environmental covariates, history of work over water or snow was associated with increased odds of XFS (OR, 3.86; 95% CI, 1.36-10.9); in Israel, there were too few people with such history for analysis. We did not identify an association between brimmed hat wear and XFS (P > .57). CONCLUSIONS AND RELEVANCE: Lifetime outdoor activities may contribute to XFS. The association with work over snow or water and the lack of association with brimmed hat wear suggests that ocular exposure to light from reflective surfaces may be an important type of exposure in XFS etiology.
Lee WJ, Sobrin L, Lee MJ, Kang MH, Seong M, Cho H. The relationship between diabetic retinopathy and diabetic nephropathy in a population-based study in Korea (KNHANES V-2,3). Invest Ophthalmol Vis Sci 2014;Abstract

PURPOSE. To determine the risk factors for and relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN), including microalbuminuria and overt nephropathy, in a population-based study of diabetes mellitus (DM) patients in Korea. METHODS. This was a population-based, cross-sectional study. From the fifth (2011, 2012) Korea National Health and Nutrition Examination Survey (KNHANES), 971 participants with type 2 DM were included. The prevalence of DR and DN was determined. Multivariate logistic regression was performed to determine risk factors, including DR, associated with DN in the Korean population. RESULTS. In DM patients, we observed a prevalence of 20.0% for any DR and 3.8% for proliferative diabetic retinopathy (PDR). Microalbuminuria prevalence was 19.3% and overt nephropathy prevalence was 5.5%. The risk factors of microalbuminuria were presence of hypertension, higher systolic blood pressure, serum hemoglobin A1c (HbA1c) and serum blood urea nitrogen level as well as the presence of PDR. The risk factors of overt nephropathy were long duration of DM, high levels of HbA1c, systolic blood pressure, total cholesterol and serum creatinine as well as the presence of DR. CONCLUSIONS. PDR is associated with microalbuminuria and DR is associated with overt nephropathy in Korean DM patients. Our findings suggest that when an ophthalmologist finds the presence of DR or PDR, timely evaluation of the patient's renal status should be recommended.

Mouw KW, Sethi RV, Yeap BY, MacDonald SM, Chen Y-LE, Tarbell NJ, Yock TI, Munzenrider JE, Adams J, Grabowski E, Mukai S, Shih HA. Proton Radiation Therapy for the Treatment of Retinoblastoma. Int J Radiat Oncol Biol Phys 2014;90(4):863-9.Abstract
PURPOSE: To investigate long-term disease and toxicity outcomes for pediatric retinoblastoma patients treated with proton radiation therapy (PRT). METHODS AND MATERIALS: This is a retrospective analysis of 49 retinoblastoma patients (60 eyes) treated with PRT between 1986 and 2012. RESULTS: The majority (84%) of patients had bilateral disease, and nearly half (45%) had received prior chemotherapy. At a median follow-up of 8 years (range, 1-24 years), no patients died of retinoblastoma or developed metastatic disease. The post-PRT enucleation rate was low (18%), especially in patients with early-stage disease (11% for patients with International Classification for Intraocular Retinoblastoma [ICIR] stage A-B disease vs 23% for patients with ICIR stage C-D disease). Post-PRT ophthalmologic follow-up was available for 61% of the preserved eyes (30 of 49): 14 of 30 eyes (47%) had 20/40 visual acuity or better, 7 of 30 (23%) had moderate visual acuity (20/40-20/600), and 9 of 30 (30%) had little or no useful vision (worse than 20/600). Twelve of 60 treated eyes (20%) experienced a post-PRT event requiring intervention, with cataracts the most common (4 eyes). No patients developed an in-field second malignancy. CONCLUSIONS: Long-term follow-up of retinoblastoma patients treated with PRT demonstrates that PRT can achieve high local control rates, even in advanced cases, and many patients retain useful vision in the treated eye. Treatment-related ocular side effects were uncommon, and no radiation-associated malignancies were observed.
Tiedemann LM, Lefebvre DR, Wan MJ, Dagi LR. Iatrogenic inferior oblique palsy: intentional disinsertion during transcaruncular approach to orbital fracture repair. J AAPOS 2014;Abstract

Hypotropia following orbital fracture repair is traditionally attributed to residual tissue entrapment, scarring, direct muscle injury, or damage to the branches of the oculomotor nerve serving the inferior oblique or inferior rectus muscles. We present a case of acquired hypotropia and incyclotropia that occurred following repair of an orbital fracture involving the floor and medial wall. In order to enable adequate visualization and treatment of the combined fractures, access via a transcaruncular approach and disinsertion of the inferior oblique muscle at its origin was necessary. Whereas the possibility of inferior oblique paresis due to repair of an orbital fracture via the transcaruncular approach has received some acknowledgment, there are no prior reports in the ophthalmic literature. Strabismus surgeons should be aware of this possibility when planning surgical correction of hypotropia and incyclotropia in similar cases.

Arafat SN, Robert M-C, Shukla AN, Dohlman CH, Chodosh J, Ciolino JB. UV cross-linking of donor corneas confers resistance to keratolysis. Cornea 2014;33(9):955-9.Abstract

PURPOSE: The aim of this study was to develop a modified ex vivo corneal cross-linking method that increases stromal resistance to enzymatic degradation for use as a carrier for the Boston keratoprosthesis. METHODS: Ex vivo cross-linking of human corneas was performed using Barron artificial anterior chambers. The corneas were deepithelialized, pretreated with riboflavin solution (0.1% riboflavin/20% dextran), and irradiated with ultraviolet A (UV-A) light (λ = 370 nm, irradiance = 3 mW/cm) for various durations. The combined effect of UV-A and gamma (γ) irradiation was also assessed using the commercially available γ-irradiated corneal donors. The corneas were then trephined and incubated at 37°C with 0.3% collagenase A solution. The time to dissolution of each cornea was compared across treatments. RESULTS: Deepithelialized corneas (no UV light, no riboflavin) dissolved in 5.8 ± 0.6 hours. Cross-linked corneas demonstrated increased resistance to dissolution, with a time to dissolution of 17.8 ± 2.6 hours (P < 0.0001). The corneal tissues' resistance to collagenase increased with longer UV-A exposure, reaching a plateau at 30 minutes. Cross-linking both the anterior and posterior corneas did not provide added resistance when compared with cross-linking the anterior corneas only (P > 0.05). γ-irradiated corneas dissolved as readily as deepithelialized controls regardless of whether they were further cross-linked (5.6 ± 1.2 hours) or not (6.1 ± 0.6 hours) (P = 0.43). CONCLUSIONS: Collagen cross-linking of the deepithelialized anterior corneal surface for 30 minutes conferred optimal resistance to in vitro keratolysis by collagenase A.

Van Tyne D, Gilmore MS. Friend turned foe: evolution of enterococcal virulence and antibiotic resistance. Annu Rev Microbiol 2014;68:337-56.Abstract
The enterococci are an ancient genus that evolved along with the tree of life. These intrinsically rugged bacteria are highly adapted members of the intestinal consortia of a range of hosts that spans the animal kingdom. Enterococci are also leading opportunistic hospital pathogens, causing infections that are often resistant to treatment with most antibiotics. Despite the importance of enterococci as hospital pathogens, the vast majority live outside of humans, and nearly all of their evolutionary history took place before the appearance of modern humans. Because hospital infections represent evolutionary end points, traits that exacerbate human infection are unlikely to have evolved for that purpose. However, clusters of traits have converged in specific lineages that are well adapted to colonize the antibiotic-perturbed gastrointestinal tracts of patients and that thrive in the hospital environment. Here we discuss these traits in an evolutionary context, as well as how comparative genomics is providing new insights into the evolution of the enterococci.
Wang S, Sengel C, Emerson MM, Cepko CL. A gene regulatory network controls the binary fate decision of rod and bipolar cells in the vertebrate retina. Dev Cell 2014;30(5):513-27.Abstract
Gene regulatory networks (GRNs) regulate critical events during development. In complex tissues, such as the mammalian central nervous system (CNS), networks likely provide the complex regulatory interactions needed to direct the specification of the many CNS cell types. Here, we dissect a GRN that regulates a binary fate decision between two siblings in the murine retina, the rod photoreceptor and bipolar interneuron. The GRN centers on Blimp1, one of the transcription factors (TFs) that regulates the rod versus bipolar cell fate decision. We identified a cis-regulatory module (CRM), B108, that mimics Blimp1 expression. Deletion of genomic B108 by CRISPR/Cas9 in vivo using electroporation abolished the function of Blimp1. Otx2 and RORβ were found to regulate Blimp1 expression via B108, and Blimp1 and Otx2 were shown to form a negative feedback loop that regulates the level of Otx2, which regulates the production of the correct ratio of rods and bipolar cells.
Farkas MH, Grant GR, White JA, Sousa ME, Consugar MB, Pierce EA. Transcriptome analyses of the human retina identify unprecedented transcript diversity and 3.5 Mb of novel transcribed sequence via significant alternative splicing and novel genes. BMC Genomics 2013;14:486.Abstract
BACKGROUND: The retina is a complex tissue comprised of multiple cell types that is affected by a diverse set of diseases that are important causes of vision loss. Characterizing the transcripts, both annotated and novel, that are expressed in a given tissue has become vital for understanding the mechanisms underlying the pathology of disease. RESULTS: We sequenced RNA prepared from three normal human retinas and characterized the retinal transcriptome at an unprecedented level due to the increased depth of sampling provided by the RNA-seq approach. We used a non-redundant reference transcriptome from all of the empirically-determined human reference tracks to identify annotated and novel sequences expressed in the retina. We detected 79,915 novel alternative splicing events, including 29,887 novel exons, 21,757 3' and 5' alternate splice sites, and 28,271 exon skipping events. We also identified 116 potential novel genes. These data represent a significant addition to the annotated human transcriptome. For example, the novel exons detected increase the number of identified exons by 3%. Using a high-throughput RNA capture approach to validate 14,696 of these novel transcriptome features we found that 99% of the putative novel events can be reproducibly detected. Further, 15-36% of the novel splicing events maintain an open reading frame, suggesting they produce novel protein products. CONCLUSIONS: To our knowledge, this is the first application of RNA capture to perform large-scale validation of novel transcriptome features. In total, these analyses provide extensive detail about a previously uncharacterized level of transcript diversity in the human retina.

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