All

Liou VD, Yoon MK. Advances in steroid sparing medical management of active thyroid eye disease. Semin Ophthalmol 2020;:1-8.Abstract
Thyroid eye disease (TED) is an autoimmune inflammatory disease of the orbit and the most common extrathyroidal manifestation of Graves disease. The release of pro-inflammatory cytokines is associated with inflammation of the ocular surface and lacrimal gland along with periorbital skin erythema and edema. Resultant tissue remodeling, fibrosis, and fat deposition can impart permanent physical changes to the ocular adnexa with effects on function and cosmesis. These changes occur in the active phase of disease, and it is during this time that steroids are often relied on to help alleviate symptoms. Due to the common and predictable side effects of long-term and high-dose steroid use, there has been a continuous effort to find alternative steroid-sparing medical management options for TED. This review highlights the various research studies that support the use of these medications.
Chen X, Lei F, Zhou C, Chodosh J, Wang L, Huang Y, Dohlman CH, Paschalis EI. Glaucoma after Ocular Surgery or Trauma: The Role of Infiltrating Monocytes and Their Response to Cytokine Inhibitors. Am J Pathol 2020;190(10):2056-2066.Abstract
Glaucoma is a frequent and devastating long-term complication following ocular trauma, including corneal surgery, open globe injury, chemical burn, and infection. Postevent inflammation and neuroglial remodeling play a key role in subsequent ganglion cell apoptosis and glaucoma. To this end, this study was designed to investigate the amplifying role of monocyte infiltration into the retina. By using three different ocular injury mouse models (corneal suture, penetrating keratoplasty, and globe injury) and monocyte fate mapping techniques, we show that ocular trauma or surgery can cause robust infiltration of bone marrow-derived monocytes into the retina and subsequent neuroinflammation by up-regulation of Tnf, Il1b, and Il6 mRNA within 24 hours. This is accompanied by ganglion cell apoptosis and neurodegeneration. Prompt inhibition of tumor necrosis factor-α or IL-1β markedly suppresses monocyte infiltration and ganglion cell loss. Thus, acute ocular injury (surgical or trauma) can lead to rapid neuroretinal inflammation and subsequent ganglion cell loss, the hallmark of glaucoma. Infiltrating monocytes play a central role in this process, likely amplifying the inflammatory cascade, aiding in the activation of retinal microglia. Prompt administration of cytokine inhibitors after ocular injury prevents this infiltration and ameliorates the damage to the retina-suggesting that it may be used prophylactically for neuroprotection against post-traumatic glaucoma.
Shah DN, Al-Moujahed A, Newcomb CW, Kaçmaz OR, Daniel E, Thorne JE, Foster SC, Jabs DA, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Sen NH, Suhler EB, Bhatt NP, Kempen JH, for Group SITEDR. Exudative Retinal Detachment in Ocular Inflammatory Diseases: Risk and Predictive Factors. Am J Ophthalmol 2020;218:279-287.Abstract
PURPOSE: This study evaluated the risk and risk factors for exudative retinal detachment (ERD) in ocular inflammatory diseases. DESIGN: Retrospective cohort study. METHODS: Patients with noninfectious ocular inflammation had been followed longitudinally between 1978 and 2007 at 4 US subspecialty uveitis centers. The main outcome measurements were occurrences of ERD and predictive factors. RESULTS: A total of 176 of 14,612 eyes with ocular inflammation presented with ERD. Among uveitis cases, Vogt-Koyanagi-Harada syndrome (VKH) (odds ratio [OR] = 109), undifferentiated choroiditis (OR = 9.18), sympathetic ophthalmia (OR = 8.43), primary or secondary panuveitis (OR = 7.09), multifocal choroiditis with panuveitis (OR = 4.51), and "other" forms of posterior uveitis (OR = 16.9) were associated with a higher prevalence of ERD. Among the 9,209 uveitic or scleritic eyes initially free of ERD and followed, 137 incident ERD cases were observed over 28,949 eye-years at risk (incidence rate = 0.47% [0.40%-0.56%/eye-year]). VKH (HR = 13.2), sympathetic ophthalmia (HR = 5.82), undifferentiated choroiditis (HR = 6.03), primary or secondary panuveitis (HR = 4.21), and rheumatoid arthritis (HR = 3.30) were significantly associated with incident ERD. A significant dose-response relationship with the prevalence and incidence of ERD were observed for AC cells and vitreous cell activity. African Americans had significantly higher prevalence and incidence of ERD. CONCLUSIONS: Other ocular inflammatory conditions in addition to VKH syndrome and posterior scleritis were associated with increased risk of ERD, indicating that ERD does not necessarily dictate a diagnosis of VKH or posterior scleritis. In addition, the relationship between ERD and inflammatory severity factors implies that inflammation is a key predictive factor associated with developing ERD and requires early and vigorous control.
Yang M, Lippestad M, Hodges RR, Fjærvoll HK, Fjærvoll KA, Bair JA, Utheim TP, Serhan CN, Dartt DA. RvE1 uses the LTB receptor BLT1 to increase [Ca] and stimulate mucin secretion in cultured rat and human conjunctival goblet cells. Ocul Surf 2020;18(3):470-482.Abstract
PURPOSE: Specialized pro-resolving lipid mediator resolvin (Rv) E1 stimulates secretion including mucins from conjunctival goblet cells. RvE1 can use both its ChemR23 receptor and the LTB receptor BLT1 to increase [Ca]. The purpose of this study was to determine the expression of ChemR23 and BLT1 and receptors on conjunctival goblet cells and the respective roles these two receptors play in goblet cell responses to RvE1. METHODS: Goblet cells were cultured from male rat or human conjunctiva from both sexes. Western blotting analysis, reverse transcription PCR and immunofluorescence microscopy were used to demonstrate the expression of ChemR23 and BLT1 in conjunctival goblet cells. High molecular weight glycoprotein secretion was determined using an enzyme-linked lectin assay. Signaling pathways were studied by measuring the increase in [Ca] using fura 2/AM. RESULTS: ChemR23 and BLT1 and receptors were present on both rat and human conjunctival goblet cells. The BLT1 inhibitors LY293111 and U75302 significantly blocked RvE1-and LTB-stimulated [Ca] increase. RvE1-and LTB-stimulated [Ca] and secretion increases were blocked by BLT1-targeted siRNA. RvE1-stimulated [Ca] and secretion increases were also blocked by ChemR23-targeted siRNA. Addition of RvE1 2 min before or simultaneously with LTB desensitized the LTB [Ca] response. Addition of RvE1 and LTB simultaneously caused secretion that was decreased compared to either response alone. CONCLUSION: RvE1, in addition to the ChemR23 receptor, uses the BLT1 receptor to increase [Ca] and stimulate secretion in both rat and human cultured conjunctival goblet cells.
FCRS AMDR, MBBS BB, MD TI, MBBS MS, MS AA, MD GDV, PhD RD, MS AK, DNB MSI, FRCSOphth WM, FRCSEd CSP, MD MP, FRCSGlasg HSL, FRCSEd TS, MD CL, MS BJ, MD NS, MS AM, DNB MP, MD KM, FRCSOphth JN, MD T-TI, DNB BK, MS BS, MD CE, PhD LR, MD A-DH, MD BB, MD IA, MD GDA, MD HCP, PhD B-AT, PhD G-LJJ, MD AS, MS BR, MS MB, MD ES, MD TA, MD NS, DNB AM, MD AS, MD VR, MS SR, MD SA, PhD SK, PhD ZM, MRCP KOM, PhD CET, PhD KJH, PhD NQD, FRCSOphth PC, MS GV. The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 165 Patients with Tubercular Anterior Uveitis. Ocul Immunol Inflamm 2020;:1-10.
Agrawal R MD FCRS, MBBS GDV, MS AA, MD TI, MD CE, FRCOphth WM, MBBS MS, PhD RD, MS AK, DNB MSI, FRCSEd CSP, MD MP, FRCSGlasg HSL, FRCSEd TS, MD CL, MS BJ, MD NS, MS AM, DNB MP, MD KM, FRCSOphth JN, MD T-TI, DNB BK, MS BS, PhD LR, MD A-DH, MD BB, MD IA, MD GDA, MD HCP, PhD B-AT, PhD G-LJJ, MD AS, MS BR, MS MB, MD ESD, MD TA, MD NS, DNB AM, MD AS, MD VR, MS SR, MD SA, PhD SK, PhD ZM, MRCP KOM, PhD CET, PhD KJH, PhD NQD, FRCSOphth PC, MS GV. Visual Morbidity in Ocular Tuberculosis - Collaborative Ocular Tuberculosis Study (COTS)-1: Report #6. Ocul Immunol Inflamm 2020;:1-9.
Li LH, Lee JC-Y, Leung HH, Lam WC, Fu Z, Lo ACY. Lutein Supplementation for Eye Diseases. Nutrients 2020;12(6)Abstract
Lutein is one of the few xanthophyll carotenoids that is found in high concentration in the macula of human retina. As synthesis of lutein within the human body is impossible, lutein can only be obtained from diet. It is a natural substance abundant in egg yolk and dark green leafy vegetables. Many basic and clinical studies have reported lutein's anti-oxidative and anti-inflammatory properties in the eye, suggesting its beneficial effects on protection and alleviation of ocular diseases such as age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, myopia, and cataract. Most importantly, lutein is categorized as Generally Regarded as Safe (GRAS), posing minimal side-effects upon long term consumption. In this review, we will discuss the chemical structure and properties of lutein as well as its application and safety as a nutritional supplement. Finally, the effects of lutein consumption on the aforementioned eye diseases will be reviewed.
Yang Y, Huang X, Ma G, Cui J, Matsubara JA, Kazlauskas A, Zhao J, Wang J, Lei H. PDGFRβ plays an essential role in patient vitreous-stimulated contraction of retinal pigment epithelial cells from epiretinal membranes. Exp Eye Res 2020;197:108116.Abstract
Platelet-derived growth factor (PDGF) is associated with clinical proliferative vitreoretinopathy (PVR), which is characterized by formation of sub- or epi-retinal membranes that consist of cells including retinal pigment epithelial (RPE) cells and extracellular matrix. RPE cells play an important role in PVR pathogenesis. Previous findings indicated that PDGF receptor (PDGFR)α was essential in experimental PVR induced by fibroblasts. In RPE cells derived from epiretinal membranes from patients with PVR (RPEMs), Akt was activated by PDGF-B but not PDGF-A, which suggested that PDGFRβ was the predominant PDGFR isoform expressed in RPEMs. Indeed, CRISPR/Cas9-mediated depletion of PDGFRβ in RPEMs attenuated patient vitreous-induced Akt activation and cellular responses intrinsic to PVR including cell proliferation, migration, and contraction. We conclude that PDGFRβ appears to be the PVR relevant PDGFR isoform in RPEMs.
Cogné B, Latypova X, Senaratne LDS, Martin L, Koboldt DC, Kellaris G, Fievet L, Le Meur G, Caldari D, Debray D, Nizon M, Frengen E, Bowne SJ, Consortium L99, Cadena EL, Daiger SP, Bujakowska KM, Pierce EA, Gorin M, Katsanis N, Bézieau S, Petersen-Jones SM, Occelli LM, Lyons LA, Legeai-Mallet L, Sullivan LS, Davis EE, Isidor B. Mutations in the Kinesin-2 Motor KIF3B Cause an Autosomal-Dominant Ciliopathy. Am J Hum Genet 2020;106(6):893-904.Abstract
Kinesin-2 enables ciliary assembly and maintenance as an anterograde intraflagellar transport (IFT) motor. Molecular motor activity is driven by a heterotrimeric complex comprised of KIF3A and KIF3B or KIF3C plus one non-motor subunit, KIFAP3. Using exome sequencing, we identified heterozygous KIF3B variants in two unrelated families with hallmark ciliopathy phenotypes. In the first family, the proband presents with hepatic fibrosis, retinitis pigmentosa, and postaxial polydactyly; he harbors a de novo c.748G>C (p.Glu250Gln) variant affecting the kinesin motor domain encoded by KIF3B. The second family is a six-generation pedigree affected predominantly by retinitis pigmentosa. Affected individuals carry a heterozygous c.1568T>C (p.Leu523Pro) KIF3B variant segregating in an autosomal-dominant pattern. We observed a significant increase in primary cilia length in vitro in the context of either of the two mutations while variant KIF3B proteins retained stability indistinguishable from wild type. Furthermore, we tested the effects of KIF3B mutant mRNA expression in the developing zebrafish retina. In the presence of either missense variant, rhodopsin was sequestered to the photoreceptor rod inner segment layer with a concomitant increase in photoreceptor cilia length. Notably, impaired rhodopsin trafficking is also characteristic of recessive KIF3B models as exemplified by an early-onset, autosomal-recessive, progressive retinal degeneration in Bengal cats; we identified a c.1000G>A (p.Ala334Thr) KIF3B variant by genome-wide association study and whole-genome sequencing. Together, our genetic, cell-based, and in vivo modeling data delineate an autosomal-dominant syndromic retinal ciliopathy in humans and suggest that multiple KIF3B pathomechanisms can impair kinesin-driven ciliary transport in the photoreceptor.
Valdes LM, Sobrin L. Uveitis Therapy: The Corticosteroid Options. Drugs 2020;80(8):765-773.Abstract
Uveitis is characterized by intraocular inflammation involving the uveal tract; its etiologies generally fall into two broad categories: autoimmune/inflammatory or infectious. Corticosteroids  are a powerful and important class of medications ubiquitous in the treatment of uveitis. They may be given systemically or locally, in the form of topical drops, periocular injection, intravitreal suspension, or intravitreal implant. This review describes each of the currently available corticosteroid treatment options for uveitis, including favorable and unfavorable characteristics of each as well as applicable clinical trials. The main advantage of corticosteroids as a whole is their ability to quickly and effectively control inflammation early on in the course of uveitis. However, they can have serious side effects, whether localized to the eye (such as cataract and elevated intraocular pressure) or systemic (such as osteonecrosis and adrenal insufficiency) and in the majority of cases of uveitis are not an appropriate option for long-term therapy.
Elhusseiny AM, Jamerson EC, Menshawey R, Tam EK, El Sayed YM. Collector Channels: Role and Evaluation in Schlemm's Canal Surgery. Curr Eye Res 2020;45(10):1181-1187.Abstract
OBJECTIVES: 1) To elucidate the role of collector channels in the aqueous humor outflow pathway 2) To suggest anatomic and functional methods of imaging collector channels in-vitro and in-vivo and 3) To discuss the role of such imaging modalities in the surgical management of glaucoma. METHODS: A thorough literature search was conducted on databases for studies published in English regarding the available methods to determine the role of collecting channels in normal and glaucomatous patients and to assess their patency. RESULTS: Intraocular pressure (IOP) exists as a balance between aqueous humor production and aqueous humor outflow. Collector channels are an essential anatomical constituent of the distal portion of the conventional aqueous humor outflow pathway. There are different surgical options for glaucoma management and with the recent advances in Schlemm's canal-based surgeries, collector channel's patency became a key factor in determining the optimum management for the glaucomatous eye. The advent of anatomic imaging methods has improved the ability to visualize collector channel morphology in-vitro, including swept-source optical coherence tomography (SS-OCT), spectral domain optical coherence tomography (SD-OCT), micro-computed tomography (micro CT), new immunohistochemistry techniques and scanning electron microscopy. The recent advent of real-time assessment of collector channel patency (including evaluation of episcleral venous outflow, observation of episcleral venous fluid wave, and tracer studies utilizing fluorescein, indocyanine green, and trypan blue) has been validated by the aforementioned anatomic imaging modalities. CONCLUSIONS: New modalities of in-vitro and in-vivo studies of collector channels provide promise to aid in the assessment of collector channel patency and individualization of surgical management for glaucoma patients.
Collett G, Elhusseiny AM, Scelfo C, Whitman MC, VanderVeen DK. Ocular injury via epinephrine auto-injector. J AAPOS 2020;Abstract
Intraocular injury by epinephrine auto-injector has been rarely reported. Toxic risk to the intraocular structures is suspected, but the evidence is inconclusive. We present the case of a 2-year-old girl who sustained an injury to her right eye by inadvertent epinephrine injection. Cataract surgery was performed to treat an increasingly opaque lens, and an intraocular lens was implanted. The visual outcome was good, with no retinal damage.

Pages