November 2016

Avedschmidt SE, Stagner AM, Eagle RC, Harocopos GJ, Dou Y, Rao RC. The Targetable Epigenetic Tumor Protein EZH2 is Enriched in Intraocular Medulloepithelioma. Invest Ophthalmol Vis Sci 2016;57(14):6242-6246.Abstract

Purpose: Intraocular medulloepithelioma (IM), the second most common primary neuroepithelial tumor of the eye, can lead to blindness in the affected eye and in rare cases, is deadly. Intraocular medulloepithelioma lacks targetable biomarkers for potential pharmacologic therapy. The purpose of this study was to identify actionable, tumor-specific proteins for potential diagnostic or therapeutic strategies. We hypothesize that the tumor-specific epigenetic enzyme EZH2 is selectively expressed in IM. Methods: We conducted a retrospective case series study of five IM from five eyes of four children and one adult. Hematoxylin and eosin (H&E) stains of sections from formalin-fixed, paraffin-embedded blocks of IM tumors were used to localize IM tumor cells in each case. Using an EZH2-specific antibody for immunohistochemistry, we semiquantitatively calculated the proportion of IM tumor cells positive for EZH2, and also assayed for EZH2 staining intensity. Results: We found that EZH2 was expressed in all IM cases but this protein was absent in nontumor ciliary body or retinal tissues. However, not all IM tumor cells expressed EZH2. Similar to retinoblastoma, moderately to poorly differentiated (primitive appearing) IM tumor cells strongly expressed EZH2; expression was weaker or absent in areas of well-formed neuroepithelial units. Conclusions: To our knowledge, this is the first study to identify an actionable tumor-specific maker, EZH2, in IM. Our findings point to the possibility of exploring the potential of EZH2 inhibitors, already in clinical trials for other cancers, for IM.

Avery RA, Katowitz JA, Fisher MJ, Heidary G, Dombi E, Packer RJ, Widemann BC, Widemann BC. Orbital/Periorbital Plexiform Neurofibromas in Children with Neurofibromatosis Type 1: Multidisciplinary Recommendations for Care. Ophthalmology 2017;124(1):123-132.Abstract

TOPIC: Children and adults with neurofibromatosis type 1 (NF1), a common autosomal dominant condition, manifest a variety of ophthalmologic conditions. Plexiform neurofibromas (PNs) involving the eyelid, orbit, periorbital, and facial structures (orbital-periorbital plexiform neurofibroma [OPPN]) can result in significant visual loss in children. Equally important, OPPNs can cause significant alteration in physical appearance secondary to proptosis, ptosis, and facial disfigurement, leading to social embarrassment and decreased self-esteem. CLINICAL RELEVANCE: Although NF1 is a relatively common disease in which routine ophthalmologic examinations are required, no formal recommendations for clinical care of children with OPPNs exist. Although medical and surgical interventions have been reported, there are no agreed-on criteria for when OPPNs require therapy and which treatment produces the best outcome. METHODS: Because a multidisciplinary team of specialists (oculofacial plastics, pediatric ophthalmology, neuro-ophthalmology, medical genetics, and neuro-oncology) direct management decisions, the absence of a uniform outcome measure that represents visual or aesthetic sequelae complicates the design of evidence-based studies and feasible clinical trials. RESULTS: In September 2013, a multidisciplinary task force, composed of pediatric practitioners from tertiary care centers experienced in caring for children with OPPN, was convened to address the lack of clinical care guidelines for children with OPPN. CONCLUSIONS: This consensus statement provides recommendations for ophthalmologic monitoring, outlines treatment indications and forthcoming biologic therapy, and discusses challenges to performing clinical trials in this complicated condition.

Dagi Glass LR, Lawrence DP, Jakobiec FA, Freitag SK. Conjunctival Melanoma Responsive to Combined Systemic BRAF/MEK Inhibitors. Ophthal Plast Reconstr Surg 2016;Abstract

This report demonstrates a unique case of conjunctival melanoma harboring a BRAF V600E mutation responsive to systemic therapy with BRAF and MEK inhibitors. While systemic therapy would not be appropriate in patients with local disease alone, it may act therapeutically in cases of higher stage ocular surface and eyelid melanoma.

Ebrahimiadib N, Modjtahedi BS, Roohipoor R, Anesi SD, Foster SC. Successful Treatment Strategies in Granulomatosis With Polyangiitis-Associated Peripheral Ulcerative Keratitis. Cornea 2016;35(11):1459-1465.Abstract

PURPOSE: Management of granulomatosis with polyangiitis (GPA)-associated peripheral ulcerative keratitis (PUK) is challenging and lacks definite guidelines. We aimed to summarize our treatment and outcome experience with patients with GPA-PUK. METHODS: The Massachusetts Eye Research and Surgery Institution patient database was searched from 2005 to 2015 to identify patients with diagnosis of PUK who suffered from GPA. Individual patient histories were examined, and treatment strategies and outcomes were summarized. RESULTS: There were 16 patients who started treatment with a mean duration follow-up of 64 months (range: 12-110 mo). Rituximab and cyclophosphamide, either alone or in combination with other agents, were the most successful agents in controlling inflammation. Rituximab was administered in 11 patients with remission being achieved in all. Cyclophosphamide successfully controlled inflammation in 50% (5/10). Two of the patients (2/5, 40%) who had achieved initial control on cyclophosphamide had flares of their PUK. Two of 11 (18%) patients on rituximab had flares of scleritis and orbital inflammation but not PUK. Two patients, one in each treatment group, stopped treatment after achieving remission after 6 months of therapy but suffered disease recurrence within 2 months of treatment cessation. CONCLUSIONS: Rituximab achieved a high rate of disease control in PUK patients with GPA and is the preferred agent in halting disease progression.

Fay A, Dolman PJ. Diseases and Disorders of the Orbit and Ocular Adnexa, 1st Edition. 1st ed. Elsevier; 2016.Abstract

Drawing from the knowledge and expertise of more than 70 contributing international experts, Diseases and Disorders of the Orbit and Ocular Adnexa thoroughly covers the state of the art in orbital and periocular disease from the perspective of a variety of specialties. Clearly written and profusely illustrated, it covers the clinical presentation, pathophysiology, natural history, and management alternatives of disease processes affecting the orbit, eyelids, lacrimal system, and upper face. With a singular focus on the diagnosis and management of orbital and ocular adnexal disease, this authoritative text gives you the information you need to excel both in practice and on exams in the specialty of ophthalmic plastic and reconstructive surgery.

Key Features

Offers an in-depth and thorough approach to the pathophysiology of oculoplastics and orbital disease, incorporating the perspectives of numerous specialties - all in one convenient volume.

  • Uses an easy-to-follow, templated format throughout so you can find what you need quickly.
  • Covers new information not included in other texts, such as antibody testing in dysthyroid conditions and a rapidly emerging array of targeted immunosuppressive medications for the treatment of inflammatory orbital disease.
  • Includes hot topics such as the classification and management of orbital inflammatory disease; vascular neoplasms and malformations; periocular dermatology; burn management; facial paralytic disease; and the pathogenesis, evaluation and management of lymphoproliferative disease.
  • Features more than 1,200 high-quality clinical, imaging, and histological illustrations that provide clear visual examples of orbital disease.
  • Written by an international team of experts from five continents (across multiple specialties including ophthalmology, dermatology, burn management, plastic surgery, otolaryngology, endocrinology, and pathology) led by Dr. Aaron Fay and Dr. Peter J. Dolman.
  • Expert Consult™ eBook version included with purchase. This enhanced eBook experience allows you to search all of the text, figures, and references from the book on a variety of devices.

Author Information
By Aaron Fay, MD, Assistant Professor, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA and Peter J Dolman, MD, FRCSC , Clinical Professor, Division Head of Oculoplastics and Orbit; Director of Fellowship Programmes, Department of Ophthalmology, University of British Columbia, Vancouver, BC, Canada


Gaier ED, Gittinger JW, Cestari DM, Miller JB. Peripapillary Capillary Dilation in Leber Hereditary Optic Neuropathy Revealed by Optical Coherence Tomographic Angiography. JAMA Ophthalmol 2016;134(11):1332-1334.
Hattori T, Takahashi H, Dana R. Novel Insights Into the Immunoregulatory Function and Localization of Dendritic Cells. Cornea 2016;35 Suppl 1:S49-S54.Abstract

Dendritic cells (DCs) are antigen-presenting cells that normally play a critical role in stimulating T-cell-dependent immune responses. However, tolerogenic DCs (CD11cMHC-IICD80CD86) induce immune tolerance by stimulating regulatory T cells (Tregs: CD4CD25Foxp3). Although tolerogenic DCs are used to treat autoimmune diseases and to prevent transplantation rejection, the mechanisms by which they regulate alloimmunity are poorly understood. Here, we review our previous studies aiming to elucidate the mechanisms involved in immune rejection of corneal allografts using a corneal transplant model. We found that donor-derived tolerogenic DCs significantly prolonged corneal allograft survival by suppressing indirect allosensitization. We also reported the precise distribution of intraepithelial corneal DCs, termed Langerhans cells (LCs: CD11cLangerinMHC-II) in the cornea, which we maintain play a critical role in regulating corneal immunity. By confocal microscopy, we constructed 3-dimensional images of corneal LCs, which demonstrated that their cell bodies are present in the basal cell layer of the corneal epithelium. Furthermore, LC dendrites extend toward the ocular surface, but do not connect to epithelial tight junctions, indicating that they cannot directly interact with ocular surface antigens. We confirm the potential of DC therapy for corneal graft rejection and report the function of intraepithelial DCs (LCs) in the normal cornea.

He M, Storr-Paulsen T, Wang AL, Ghezzi CE, Wang S, Fullana M, Karamichos D, Utheim TP, Islam R, Griffith M, Islam MM, Hodges RR, Wnek GE, Kaplan DL, Dartt DA. Artificial Polymeric Scaffolds as Extracellular Matrix Substitutes for Autologous Conjunctival Goblet Cell Expansion. Invest Ophthalmol Vis Sci 2016;57(14):6134-6146.Abstract

Purpose: We fabricated and investigated polymeric scaffolds that can substitute for the conjunctival extracellular matrix to provide a substrate for autologous expansion of human conjunctival goblet cells in culture. Methods: We fabricated two hydrogels and two silk films: (1) recombinant human collagen (RHC) hydrogel, (2) recombinant human collagen 2-methacryloylxyethyl phosphorylcholine (RHC-MPC) hydrogel, (3) arginine-glycine-aspartic acid (RGD) modified silk, and (4) poly-D-lysine (PDL) coated silk, and four electrospun scaffolds: (1) collagen, (2) poly(acrylic acid) (PAA), (3) poly(caprolactone) (PCL), and (4) poly(vinyl alcohol) (PVA). Coverslips and polyethylene terephthalate (PET) were used for comparison. Human conjunctival explants were cultured on scaffolds for 9 to 15 days. Cell viability, outgrowth area, and the percentage of cells expressing markers for stratified squamous epithelial cells (cytokeratin 4) and goblet cells (cytokeratin 7) were determined. Results: Most of cells grown on all scaffolds were viable except for PCL in which only 3.6 ± 2.2% of the cells were viable. No cells attached to PVA scaffold. The outgrowth was greatest on PDL-silk and PET. Outgrowth was smallest on PCL. All cells were CK7-positive on RHC-MPC while 84.7 ± 6.9% of cells expressed CK7 on PDL-silk. For PCL, 87.10 ± 3.17% of cells were CK7-positive compared to PET where 67.10 ± 12.08% of cells were CK7-positive cells. Conclusions: Biopolymer substrates in the form of hydrogels and silk films provided for better adherence, proliferation, and differentiation than the electrospun scaffolds and could be used for conjunctival goblet cell expansion for eventual transplantation once undifferentiated and stratified squamous cells are included. Useful polymer scaffold design characteristics have emerged from this study.

Hodges RR, Li D, Shatos MA, Serhan CN, Dartt DA. Lipoxin A4 Counter-regulates Histamine-stimulated Glycoconjugate Secretion in Conjunctival Goblet Cells. Sci Rep 2016;6:36124.Abstract

Conjunctival goblet cells synthesize and secrete mucins which play an important role in protecting the ocular surface. Pro-resolution mediators, such as lipoxin A4 (LXA4), are produced during inflammation returning the tissue to homeostasis and are also produced in non-inflamed tissues. The purpose of this study was to determine the actions of LXA4 on cultured human conjunctival goblet cell mucin secretion and increase in intracellular [Ca(2+)] ([Ca(2+)]i) and on histamine-stimulated responses. LXA4 increased mucin secretion and [Ca(2+)]i, and activated ERK1/2 in human goblet cells. Addition of LXA4 before resolvin D1 (RvD1) decreased RvD1 responses though RvD1 did not block LXA4 responses. LXA4 inhibited histamine-stimulated increases in mucin secretion, [Ca(2+)]i, and ERK1/2 activation through activation of β-adrenergic receptor kinase 1. We conclude that conjunctival goblet cells respond to LXA4 through the ALX/FPR2 receptor to maintain homeostasis of the ocular surface and regulate histamine responses and could provide a new therapeutic approach for allergic conjunctivitis and dry eye diseases.

Ismail AM, Lee JS, Dyer DW, Seto D, Rajaiya J, Chodosh J. Selection Pressure in the Human Adenovirus Fiber Knob Drives Cell Specificity in Epidemic Keratoconjunctivitis. J Virol 2016;90(21):9598-9607.Abstract

Human adenoviruses (HAdVs) contain seven species (HAdV-A to -G), each associated with specific disease conditions. Among these, HAdV-D includes those viruses associated with epidemic keratoconjunctivitis (EKC), a severe ocular surface infection. The reasons for corneal tropism for some but not all HAdV-Ds are not known. The fiber protein is a major capsid protein; its C-terminal "knob" mediates binding with host cell receptors to facilitate subsequent viral entry. In a comprehensive phylogenetic analysis of HAdV-D capsid genes, fiber knob gene sequences of HAdV-D types associated with EKC formed a unique clade. By proteotyping analysis, EKC virus-associated fiber knobs were uniquely shared. Comparative structural modeling showed no distinct variations in fiber knobs of EKC types but did show variation among HAdV-Ds in a region overlapping with the known CD46 binding site in HAdV-B. We also found signature amino acid positions that distinguish EKC from non-EKC types, and by in vitro studies we showed that corneal epithelial cell tropism can be predicted by the presence of a lysine or alanine at residue 240. This same amino acid residue in EKC viruses shows evidence for positive selection, suggesting that evolutionary pressure enhances fitness in corneal infection, and may be a molecular determinant in EKC pathogenesis. IMPORTANCE: Viruses adapt various survival strategies to gain entry into target host cells. Human adenovirus (HAdV) types are associated with distinct disease conditions, yet evidence for connections between genotype and cellular tropism is generally lacking. Here, we provide a structural and evolutionary basis for the association between specific genotypes within HAdV species D and epidemic keratoconjunctivitis, a severe ocular surface infection. We find that HAdV-D fiber genes of major EKC pathogens, specifically the fiber knob gene region, share a distinct phylogenetic clade. Deeper analysis of the fiber gene revealed that evolutionary pressure at crucial amino acid sites has a significant impact on its structural conformation, which is likely important in host cell binding and entry. Specific amino acids in hot spot residues provide a link to ocular cell tropism and possibly to corneal pathogenesis.

Klevebro S, Lundgren P, Hammar U, Smith LE, Bottai M, Domellöf M, Löfqvist C, Hallberg B, Hellström A. Cohort study of growth patterns by gestational age in preterm infants developing morbidity. BMJ Open 2016;6(11):e012872.Abstract

OBJECTIVES: To examine differences in growth patterns in preterm infants developing major morbidities including retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC) and intraventricular haemorrhage (IVH). STUDY DESIGN: Cohort study of 2521 infants born at a gestational age (GA) of 23-30 weeks from 11 level III neonatal intensive care units in USA and Canada, and 3 Swedish population-based cohorts. OUTCOMES: Birth weight and postnatal weight gain were examined relative to birth GA and ROP, BPD, NEC and IVH development. RESULTS: Among infants with a birth GA of 25-30 weeks, birth weight SD score and postnatal weight were lower in those developing ROP and BPD. Infants developing ROP showed lower growth rates during postnatal weeks 7-9 in the 23-24 weeks GA group, during weeks 4-6 in the 25-26 weeks GA group and during weeks 1-5 in the 27-30 weeks GA group. Infants with BPD born at 27-30 weeks GA showed lower growth rates during postnatal weeks 3-5. Infants with NEC had lower growth rates after postnatal week 6 in all GA groups, with no significant differences in birth weight SD score. IVH was not associated with prenatal or postnatal growth. CONCLUSIONS: In this cohort study of extremely preterm infants, we found that the postnatal growth pattern was associated with morbidities such as ROP, BPD and NEC as well as with gestational age at birth.

Kocaba V, Damour O, Auxenfans C, Burillon C. [Limbal stem cell deficiency management. A review]. J Fr Ophtalmol 2016;39(9):791-803.Abstract

Limbal stem cell deficiency is predominantly caused by severe eye burns resulting in a decreased or a complete ablation of the regenerative potential of these stem cells. The inability to reconstruct the corneal epithelium further leads conjunctivalization of the gimbal-epithelial barrier. These abnormalities collectively result in the progressive opacification of the cornea responsible for blindness that is driven by chronic corneal ulceration and neovascularization. The underlying pathology of the cornea affects the homeostasis of the neighboring conjunctiva, eyelids, and tear film. Therefore, the ocular reconstruction to treat limbal stem cell deficiency is quite prolonged and involves a continued treatment plan. The management of limbal stem cell deficiency has undergone a multitude of changes over the past several decades. The understanding of limbal anatomy and physiology, as well as therapeutic advances in the stem cell field have propelled the development of new treatments offering new hope to severely disabled patients. Cultivated limbal epithelial and oral mucosal epithelial transplantations are therefore viable alternatives that could be utilized for the treatment of limbal stem cell deficiency.

Lee DJ, Preble J, Lee S, Foster SC, Taylor AW. MC5r and A2Ar Deficiencies During Experimental Autoimmune Uveitis Identifies Distinct T cell Polarization Programs and a Biphasic Regulatory Response. Sci Rep 2016;6:37790.Abstract

Autoantigen-specific regulatory immunity emerges in the spleen of mice recovering from experimental autoimmune uveitis (EAU), a murine model for human autoimmune uveoretinitis. This regulatory immunity provides induced tolerance to ocular autoantigen, and requires melanocortin 5 receptor (MC5r) expression on antigen presenting cells with adenosine 2 A receptor (A2Ar) expression on T cells. During EAU it is not well understood what roles MC5r and A2Ar have on promoting regulatory immunity. Cytokine profile analysis during EAU revealed MC5r and A2Ar each mediate distinct T cell responses, and are responsible for a functional regulatory immune response in the spleen. A2Ar stimulation at EAU onset did not augment this regulatory response, nor bypass the MC5r requirement to induce regulatory immunity. The importance of this pathway in human autoimmune uveitis was assayed. PBMC from uveitis patients were assayed for MC5r expression on monocytes and A2Ar on T cells, and comparison between uveitis patients and healthy controls had no significant difference. The importance for MC5r and A2Ar expression in EAU to promote the induction of protective regulatory immunity, and the expression of MC5r and A2Ar on human immune cells, suggests that it may be possible to utilize the melanocortin-adenosinergic pathways to induce protective immunity in uveitic patients.

Liegl R, Löfqvist C, Hellström A, Smith LEH. IGF-1 in retinopathy of prematurity, a CNS neurovascular disease. Early Hum Dev 2016;102:13-19.Abstract

The retina is part of the central nervous system and both the retina as well as the brain can suffer from severe damage after very preterm birth. Retinopathy of prematurity is one of the major causes of blindness in these children and brain neuronal impairments including cognitive defects, cerebral palsy and intraventricular hemorrhage (IVH) are also complications of very preterm birth. Insulin-like growth factor 1 (IGF-1) acts to promote proliferation, maturation, growth and survival of neural cells. Low levels of circulating IGF-1 are associated with ROP and defects in the IGF-1 gene are associated with CNS disorders including learning deficits and brain growth restriction. Treatment of preterm infants with recombinant IGF-1 may potentially prevent ROP and CNS disorders. This review compares the role of IGF-1 in ROP and CNS disorders. A recent phase 2 study showed a positive effect of IGF-1 on the severity of IVH but no effect on ROP. A phase 3 trial is planned.

Mantopoulos D, Bouzika P, Tsakris A, Pawlyk BS, Sandberg MA, Miller JW, Rizzo Iii JF, Vavvas DG, Cestari DM. An Experimental Animal Model of Photodynamic Optic Nerve Head Injury (PONHI). Curr Eye Res 2016;41(11):1498-1506.Abstract

PURPOSE: Anterior ischemic optic neuropathy (AION) is the most common cause of non-glaucomatous optic nerve head (ONH) injury among older adults. AION results from a sudden ischemic insult to the proximal portion of the optic nerve, typically leading to visual impairment. Here, we present an experimental model of photodynamically induced ONH injury that can be used to study neuroprotective modalities. METHODS: Intraperitoneal injection of mesoporphyrin IX was followed by photodynamic treatment of the ONH in one eye of Brown-Norway rats; the fellow eye received the reverse sequence as a sham control. Fluorescein angiography (FA), spectral domain optical coherence tomography (SD-OCT), and visual evoked potential (VEP) recordings were performed at different time points following laser treatment. Immunohistochemistry was used to monitor apoptotic cell death (TUNEL) and macrophage infiltration (CD68). Cytokine levels were evaluated using enzyme-linked immunosorbent assay (ELISA). RESULTS: FA showed early hyperfluorescence and late leakage of the ONH, while SD-OCT revealed optic nerve edema. No leakage or other abnormalities were detected in control eyes. VEPs were significantly reduced in amplitude and showed prolonged responses compared to sham eyes. The number of apoptotic retinal ganglion cells was elevated one day after laser treatment (13.77 ± 4.49, p < 0.01) and peaked on day 7 (57.22 ± 11.34, p < 0.01). ONH macrophage infiltration also peaked on day 7 (101.8 ± 9.8, p < 0.05). ELISAs performed showed upregulation of macrophage chemoattractant protein-1 and macrophage inflammatory protein-2 on days 3 and 1, respectively. CONCLUSIONS: Photodynamic treatment of the ONH after administration of mesoporphyrin IX leads to macroscopic, histologic, and physiologic evidence of ONH injury. Given the long half-life of mesoporphyrin IX and the ease of intraperitoneal injections, this new model of photodynamically induced ONH injury may be a useful tool for studying optic nerve injury and possible neuroprotective treatments.

McGrath ER, Batra A, Lam AD, Rizzo JF, Cole AJ. Clinical Reasoning: A 64-year-old man with visual distortions. Neurology 2016;87(21):e252-e256.
Mikolajczak J, Zimmermann H, Kheirkhah A, Kadas EM, Oberwahrenbrock T, Muller R, Ren A, Kuchling J, Dietze H, Prüss H, Paul F, Hamrah P, Brandt AU. Patients with multiple sclerosis demonstrate reduced subbasal corneal nerve fibre density. Mult Scler 2016;Abstract

BACKGROUND: Many studies in multiple sclerosis (MS) have investigated the retina. Little, however, is known about the effect of MS on the cornea, which is innervated by the trigeminal nerve. It is the site of neural-immune interaction with local dendritic cells reacting in response to environmental stimuli. OBJECTIVE: This study aims to investigate the effect of MS on corneal nerve fibres and dendritic cells in the subbasal nerve plexus using in vivo confocal microscopy (IVCM). METHODS: We measured the corneal nerve fibre and dendritic cell density in 26 MS patients and matched healthy controls using a Heidelberg Retina Tomograph with cornea module. Disease severity was assessed with the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale, visual acuity and retinal optical coherence tomography. RESULTS: We observed significant reduction in total corneal nerve fibre density in MS patients compared to controls. Dendritic cell density was similar in both groups. Reduced total nerve fibre density was associated with worse clinical severity but not with previous clinical trigeminal symptoms, retinal neuro-axonal damage, visual acuity or disease duration. CONCLUSION: Corneal nerve fibre density is a promising new imaging marker for the assessment of disease severity in MS and should be investigated further.

Pasquale LR, Hyman L, Wiggs JL, Rosner BA, Joshipura K, McEvoy M, McPherson ZE, Danias J, Kang JH. Prospective Study of Oral Health and Risk of Primary Open-Angle Glaucoma in Men: Data from the Health Professionals Follow-up Study. Ophthalmology 2016;123(11):2318-2327.Abstract

PURPOSE: Tooth loss or periodontal disease is associated with systemic endothelial dysfunction, which has been implicated in primary open-angle glaucoma (POAG). The relationship between oral health and POAG has received limited attention. Thus, we evaluated the association between oral health history and risk of POAG and POAG subtypes. DESIGN: Prospective cohort study. PARTICIPANTS: Health Professionals Follow-up Study participants (40 536 men) followed biennially from 1986 to 2012. At each 2-year risk period, eligible participants were aged 40+ years, were free of POAG, and reported eye examinations. METHODS: By using validated questions, we updated participants' status on number of natural teeth, teeth lost, periodontal disease with bone loss, and root canal treatments. MAIN OUTCOME MEASURES: During follow-up, 485 incident cases of POAG were confirmed with medical records and classified into subtypes defined by intraocular pressure (IOP; ≥ or <22 mmHg) or visual field (VF) loss pattern at diagnosis (peripheral loss only or early paracentral loss). Multivariable relative risks (MVRRs) and 95% confidence intervals (CIs) were estimated. RESULTS: Number of natural teeth, periodontal disease, and root canal treatment were not associated with POAG. However, compared with no report of tooth loss, a report of losing teeth within the past 2 years was associated with a 1.45-fold increased risk of POAG (95% CI, 1.06-1.97); in particular, a report within the past 2 years of both losing teeth and having a prevalent diagnosis of periodontal disease was associated with a 1.85-fold increased risk of POAG (95% CI, 1.07-3.18). The associations with recent tooth loss were not significantly different for the POAG subtypes (P for heterogeneity ≥0.36), although associations were strongest in relation to the POAG subtypes with IOP <22 mmHg (MVRR, 1.93; 95% CI, 1.09-3.43) and early paracentral VF loss (MVRR, 2.27; 95% CI, 1.32-3.88). CONCLUSIONS: Although the number of natural teeth was not associated with risk of POAG, recent tooth loss was associated with an increased risk of POAG. Because these findings may be due to chance, they need confirmation in larger studies.

Rameh LE, Mackey AM. IQGAP1 makes PI(3)K signalling as easy as PIP, PIP2, PIP3. Nat Cell Biol 2016;18(12):1263-1265.Abstract

Despite being one of the most studied signalling pathways, precisely how phospholipid synthesis is regulated in the phosphoinositide signalling cascade remains unclear. The scaffold protein IQGAP1 is now shown to orchestrate the assembly of a multi-enzyme complex that streamlines PtdIns(3,4,5)P3 synthesis to facilitate Akt activation in response to extracellular stimuli.

Sehic A, Guo S, Cho K-S, Corraya RM, Chen DF, Utheim TP. Electrical Stimulation as a Means for Improving Vision. Am J Pathol 2016;186(11):2783-2797.Abstract

Evolving research has provided evidence that noninvasive electrical stimulation (ES) of the eye may be a promising therapy for either preserving or restoring vision in several retinal and optic nerve diseases. In this review, we focus on minimally invasive strategies for the delivery of ES and accordingly summarize the current literature on transcorneal, transorbital, and transpalpebral ES in both animal experiments and clinical studies. Various mechanisms are believed to underlie the effects of ES, including increased production of neurotrophic agents, improved chorioretinal blood circulation, and inhibition of proinflammatory cytokines. Different animal models have demonstrated favorable effects of ES on both the retina and the optic nerve. Promising effects of ES have also been demonstrated in clinical studies; however, all current studies have a lack of randomization and/or a control group (sham). There is thus a pressing need for a deeper understanding of the underlying mechanisms that govern clinical success and optimization of stimulation parameters in animal studies. In addition, such research should be followed by large, prospective, clinical studies to explore the full potential of ES. Through this review, we aim to provide insight to guide future research on ES as a potential therapy for improving vision.