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A systematic review of cellular therapies for the treatment of limbal stem cell deficiency affecting one or both eyes
F.C.FigueiredoaJ.M.GlanvillebM.ArberbE.CarrbG.RydevikcJ.HoggaA.OkonkwoaG.FigueiredoaM.LakodF.WhiterbK.Wilsonb
doi : 10.1016/j.jtos.2020.12.008
Volume 20, April 2021, Pages 48-61
This systematic review (SR) assessed the efficacy, safety and cost-effectiveness of cell-based therapy to manage limbal stem cell deficiency (LSCD), a sight-threatening orphan condition most frequently associated with severe chemical or thermal burns. LSCD has historically been treated by transplanting limbal tissue. In 1997, a new treatment, cultured limbal epithelial autografts, was described for unilateral LSCD. In cases of bilateral disease cultured autologous oral mucosa stem cells have been used. The relative efficacy of different cultured tissue procedures is unknown.
Ocular surface disease associated with immune checkpoint inhibitor therapy
Royce B.ParkaSandeepJainbHuiHanaJenniferParkc
doi : 10.1016/j.jtos.2021.02.004
Volume 20, April 2021, Pages 115-129
Immune-related adverse events (irAEs) is a term used to describe the various toxicities associated with immune checkpoint inhibitor (ICI) use. As this class of cancer immunotherapy grows, the diversity of documented irAEs also continues to expand. Ocular toxicities secondary to ICI use are relatively rare, with dry eye and uveitis as the most frequently reported ocular side effects. This article specifically investigates the relationship between ocular surface disease and ICI therapy through a review of the existing literature. Dry eye disease (DED), conjunctivitis, and keratitis were the most commonly reported irAEs affecting the ocular surface across the 29 studies reviewed. Keratoplasty graft rejection was also described in two case reports. Our review of eight clinical trials found the incidence of DED, the most common ocular surface irAE, to range from 1 to 4%. Nearly all cases of ocular surface irAEs were graded as mild or moderate in severity and were often self-limited or controlled with conservative treatment. Duration of checkpoint inhibitor use prior to onset of ocular surface side effects varied widely, ranging from days to months. Ocular surface toxicities associated with checkpoint immunotherapy appear to be under-reported and under-investigated. Further work remains to be done to investigate the full breadth of ocular surface pathologies and the molecular mechanisms by which these toxicities occur.
The ocular surface immune system through the eyes of aging
Jeremias G.GallettiaCintia S.de Paivab
doi : 10.1016/j.jtos.2021.02.007
Volume 20, April 2021, Pages 139-162
Since the last century, advances in healthcare, housing, and education have led to an increase in life expectancy. Longevity is accompanied by a higher prevalence of age-related diseases, such as cancer, autoimmunity, diabetes, and infection, and part of this increase in disease incidence relates to the significant changes that aging brings about in the immune system. The eye is not spared by aging either, presenting with age-related disorders of its own, and interestingly, many of these diseases have immune pathophysiology. Being delicate organs that must be exposed to the environment in order to capture light, the eyes are endowed with a mucosal environment that protects them, the so-called ocular surface. As in other mucosal sites, immune responses at the ocular surface need to be swift and potent to eliminate threats but are at the same time tightly controlled to prevent excessive inflammation and bystander damage. This review will detail how aging affects the mucosal immune response of the ocular surface as a whole and how this process relates to the higher incidence of ocular surface disease in the elderly.
Corneal neurotization for neurotrophic keratopathy: Review of surgical techniques and outcomes
Catherine Y.LiuaAndrea C.ArteagabSammie E.FungaM. SoledadCortinabIlya M.LeyngoldcVinay K.Aakalub
doi : 10.1016/j.jtos.2021.02.010
Volume 20, April 2021, Pages 163-172
Neurotrophic keratopathy is a degenerative disease in which damage to the corneal nerves leads to corneal hypoesthesia. Injuries to neurotrophic corneas are notoriously difficult to treat and have traditionally been approached with supportive management. However, recent progress in the field of corneal neurotization has given new direction for addressing nerve loss directly by stimulating new nerve growth onto the cornea from nearby sensory nerves transferred to the perilimbal region. Herein, we review the surgical techniques utilized in corneal neurotization, including direct transfers and the use of nerve grafts. Considerations in surgical approach, as well as factors that influence prognosis and outcomes of the surgical intervention are also discussed.
Mesenchymal stromal cells for corneal transplantation: Literature review and suggestions for successful clinical trials
Joo YounOhabEunjaeKimcYoung InYunaRyang HwaLeec
doi : 10.1016/j.jtos.2021.02.002
Volume 20, April 2021, Pages 185-194
Corneal transplantation is a routine procedure for patients with corneal blindness. Despite the streamlining of surgical techniques and deeper understanding of the cellular and molecular pathways mediating rejection, corticosteroids are still the main immunosuppressive regimen in corneal transplantation, and the 15-year survival of corneal transplants remains as low as 50%, which is poorer than that for most solid organ transplants. Recently, mesenchymal stromal cells (MSCs) with unique regenerative and immune-modulating properties have emerged as a promising cell therapy to promote transplant tolerance, minimize the use of immunosuppressants, and prevent chronic rejection. Here, we review the literature on preclinical studies of MSCs for corneal transplantation and summarize the key findings from clinical trials with MSCs in solid organ transplantation. Finally, we highlight current issues and challenges regarding MSC therapies and suggest strategies for safe and effective MSC-based therapies in clinical transplantation.
Epidemiology, economic and humanistic burdens of Ocular Surface Chemical Injury: A narrative review
Afsara A.AhmmedabDarren Shu JengTingcdFrancisco C.Figueiredoef
doi : 10.1016/j.jtos.2021.02.006
Volume 20, April 2021, Pages 199-211
Ocular surface chemical injury (OSCI) is a common type of ocular emergency that can potentially cause significant and permanent visual impairment. However, the global prevalence, demographic factors, socioeconomic burden, and psychological impact of OSCI have not been well investigated or reported. This review aims to provide a comprehensive overview of these aspects, highlight gaps in the literature, and advocate key strategies in reducing the incidence of OSCI. OSCI was responsible for 0.1–15% of all ocular emergency presentations, with an estimated incidence of 5.1–50 per 100,000 population-year. Young working adult men were the most at-risk group, though high rates of OSCI were also observed in young children in developed countries, especially from detergent pods. Low- and middle-income countries were noted to have higher proportions of assault-related and pediatric OSCI cases, often with more severe presentations. Direct and indirect costs for some hospitalized patients led to loss of all personal and household income after the injury. Emergency department costs in the United States were estimated at $106.7 million over four years and costs of treating long term complications such as glaucoma were estimated to be as high as $93,003 over five years. Significant negative impacts on visual and health-related quality of life and psychological well-being have been reported after injury, with higher rates of anxiety, depression, and psychological distress compared to the general population.
Aggregated neutrophil extracellular traps occlude Meibomian glands during ocular surface inflammation
AparnaMahajanaLenkaHas?kov?abUlrikeHampelcAnikaGrüneboomaXiaomeiShanaIrmgardHerrmannaFabianGarreisdFelixBockeJasminKnopfaJeeshanSinghaChristineSchaueraSiddharthMahajanfMoritzLeppkesgFriedrichPaulsendUrsulaSchl?tzer-SchrehardtfVeitKrennhAnselmJünemanniBettinaHohbergerf…Luis E.Mu?oza1
doi : 10.1016/j.jtos.2020.12.005
Volume 20, April 2021, Pages 1-12
Obstructive Meibomian gland dysfunction (MGD) is one of the leading causes of evaporative dry eye disease. Meibomian glands at the eyelid secrete lipids that prevent evaporation of the aqueous tear film. The pathogenesis of obstructive MGD is incompletely understood to date. Herein, we aim to investigate the pathogenesis of obstructive MGD using murine and human samples with various forms of ocular surface inflammation.
The relationship between dry eye and sleep quality
Morten SchjervenMagnoabTor PaaskeUtheimaHaroldSniedercChristopher J.HammonddeJelleVehofbcd
doi : 10.1016/j.jtos.2020.12.009
Volume 20, April 2021, Pages 13-19
Sleep is an important determinant of health and quality of life. This study aimed to clarify the association between dry eye and sleep quality using a large population-based cohort.
Single-cell transcriptomics identifies limbal stem cell population and cell types mapping its differentiation trajectory in limbal basal epithelium of human cornea
De-QuanLia1SangbaeKimb1Jin-MiaoLiac1QianmiaoGaodJongsuChoibFangBianaJiaoyueHuaYunZhangaJinLiaRongLuacYumeiLibStephen C.PflugfelderaHongyuMiaodRuiChenb
doi : 10.1016/j.jtos.2020.12.004
Volume 20, April 2021, Pages 20-32
This study aimed to uncover novel cell types in heterogenous basal limbus of human cornea for identifying LSC at single cell resolution.
Saturation of cholesteryl esters produced by human meibomian gland epithelial cells after treatment with rosiglitazone
Jillian F.ZiemanskiaLandonWilsonbStephenBarnesbKelly K.Nicholsa
doi : 10.1016/j.jtos.2020.11.011
Volume 20, April 2021, Pages 39-47
The purpose of this study was to compare the cholesteryl ester (CE) profiles expressed from human meibomian gland epithelial cells (HMGECs) in response to rosiglitazone-induced differentiation to that of normal human meibum.
Developing evidence-based guidance for the treatment of dry eye disease with artificial tear supplements: A six-month multicentre, double-masked randomised controlled trial
Jennifer P.CraigabdAlexMuntzaMichael T.M.WangaDoerteLuensmannbJacquelineTancSoniaTrave HuartedAlly L.XueaLyndonJonesbceMark D.P.WillcoxcJames S.Wolffsohnd
doi : 10.1016/j.jtos.2020.12.006
Volume 20, April 2021, Pages 62-69
To assess the six-month therapeutic profiles of lipid and non-lipid-based artificial tear supplements in managing dry eye disease (DED).
Pigment epithelium-derived factor (PEDF) plays anti-inflammatory roles in the pathogenesis of dry eye disease
BaikaiMaabYifanZhouabRongjunLiuabKaiZhangcdTingtingYangabChenxiHuabYufeiGaoabfQianqianLanabeYiyunLiuabXiulanYangcdHongQiab
doi : 10.1016/j.jtos.2020.12.007
Volume 20, April 2021, Pages 70-85
To investigate the expression of pigment epithelium-derived factor (PEDF) in ocular surface in dry eye disease (DED) and its anti-inflammatory roles and mechanisms, clinically and by experiments in vivo and in vitro.
Neuroanatomy and neurochemistry of rat cornea: Changes with age
JiuchengHeabThang LuongPhamaHaydee E.P.Bazanab
doi : 10.1016/j.jtos.2020.11.005
Volume 20, April 2021, Pages 86-94
To characterize the entire rat corneal nerve architecture, the changes that occur with aging, and its sensory, sympathetic, and parasympathetic fiber distribution.
Light cycle phase advance as a model for jet lag reprograms the circadian rhythms of murine extraorbital lacrimal glands
ShenzhenHuangXinweiJiaoDingliLuXiaotingPeiDiQiZhijieLi
doi : 10.1016/j.jtos.2021.02.001
Volume 20, April 2021, Pages 95-114
Jet lag causes a disruption in physiological rhythms in humans. This study aims to explore the extent to which jet lag affects the circadian rhythmicity in the lacrimal glands.
Low-dose naltrexone is effective and well-tolerated for modulating symptoms in patients with neuropathic corneal pain
GabrielaDieckmannabM. CuneytOzmenabStephanie M.CoxabRyan C.EngertaPedramHamrahab
doi : 10.1016/j.jtos.2020.12.003
Volume 20, April 2021, Pages 33-38
Neuropathic corneal pain (NCP) is caused by damage or disease of the somatosensory nervous system that innervates the cornea and presents with symptoms of pain or persistent unpleasant sensations, such as burning, dryness, or light sensitivity. This retrospective study aims to assess the efficacy and tolerability of low-dose naltrexone (LDN) in refractory NCP patients.
Effect of therapeutic UVC on corneal DNA: Safety assessment for potential keratitis treatment
SanjayMarasiniaOdunayo O.MugishobSimonSwiftcHannahReadcIlva D.RupenthalbSimon J.DeanaJennifer P.Craiga
doi : 10.1016/j.jtos.2021.02.005
Volume 20, April 2021, Pages 130-138
Antimicrobial ultraviolet C (UVC) has proven efficacy in vitro against keratitis isolates and has potential to treat corneal infection if safety can be confirmed.
Toward electron-beam sterilization of a pre-assembled Boston keratoprosthesis
SinaSharifiaHannahSharifiaCurtisGuildbMohammad MirazulIslamaKhoa D.TrancCorrinaPatzercClaes H.DohlmanaEleftherios I.PaschalisaMiguelGonzalez-AndradesadJamesChodosha
doi : 10.1016/j.jtos.2021.02.009
Volume 20, April 2021, Pages 176-184
To evaluate the effects of electron-beam (E-beam) irradiation on the human cornea and the potential for E-beam sterilization of Boston keratoprosthesis (BK) devices when pre-assembled with a donor cornea prior to sterilization.
Human leukocyte antigen class I and II genes associated with dipyrone-related Stevens-Johnson syndrome and severe ocular complications in a Brazilian population
Tais HitomiWakamatsua1MayumiUetab1ChikaraInouebKarita AntunesCostaaLa?s YumiSakanocJuliana Maria F.SallumaJosé ?lvaroPereira GomesaShigeruKinoshitab
doi : 10.1016/j.jtos.2021.02.008
Volume 20, April 2021, Pages 173-175
The micronucleus cytome assay – A fast tool for DNA damage screening in human conjunctival epithelial cells
KaterinaJirsovaaVieraVeselaaPavlinaSkalickabEvaRuzickovabJohanaGlezgovabTomasZimacMariaDusinskadAndrewCollinseJanBednara
doi : 10.1016/j.jtos.2021.02.011
Volume 20, April 2021, Pages 195-198
To assess whether the micronucleus cytome assay (MCyt) reliably detects DNA damage occurring in control and pathological superficial epithelial cells from human conjunctiva.
Bibliometric analysis of the meibomian gland literature
Jason J.NicholsaLyndon W.JonesbcPhilip B.MorgandNathanEfrone
doi : 10.1016/j.jtos.2021.03.004
Volume 20, April 2021, Pages 212-214
What is an adequate and well controlled study?
Gary D.Novackab
doi : 10.1016/j.jtos.2021.02.003
Volume 20, April 2021, Pages 215-218
