Frontiers in ophthalmology最新文献

{"title":"Update on non-infectious uveitis treatment: anti-TNF-alpha and beyond.","authors":"Khushboo Chauhan, Mudit Tyagi","doi":"10.3389/fopht.2024.1412930","DOIUrl":"10.3389/fopht.2024.1412930","url":null,"abstract":"<p><p>Non-infectious uveitis (NIU) encompasses a range of conditions marked by inflammation within various layers of the eye. NIU is a significant contributor to irreversible vision loss among the working-age population in developed countries. The aim of treating uveitis is to manage inflammation, prevent its recurrences and to restore or salvage vision. Presently, the standard treatment protocol for NIU involves initiating corticosteroids as the primary therapeutic agents, although more aggressive approaches and steroid sparing agent may be necessary in certain cases. These advanced treatments option include synthetic immunosuppressants like antimetabolites, calcineurin inhibitors and alkylating agents. For patients who exhibit an intolerance or resistance to corticosteroids and conventional immunosuppressive therapies, biologic agents have emerged as a promising alternative. Notably, among the biologic treatments evaluated, TNF-α inhibitors, anti-CD20 therapy and alkylating agents have shown considerable efficacy. In this review, we delve into the latest evidence surrounding the effectiveness of biologic therapy and introduce novel therapeutic strategies targeting immune components as potential avenues for advancing treatment of NIU.</p>","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-throughput ultrastructural analysis of macular telangiectasia type 2.","authors":"Charles L Zucker, Paul S Bernstein, Richard L Schalek, Jeff W Lichtman, John E Dowling","doi":"10.3389/fopht.2024.1428777","DOIUrl":"10.3389/fopht.2024.1428777","url":null,"abstract":"<p><strong>Introduction: </strong>Macular Telangiectasia type 2 (MacTel), is an uncommon form of late-onset, slowly-progressive macular degeneration. Associated with regional Müller glial cell loss in the retina and the amino acid serine synthesized by Müller cells, the disease is functionally confined to a central retinal region - the MacTel zone.</p><p><strong>Methods: </strong>We have used high-throughput multi-resolution electron microscopy techniques, optimized for disease analysis, to study the retinas from two women, mother and daughter, aged 79 and 48 years respectively, suffering from MacTel.</p><p><strong>Results: </strong>In both eyes, the principal observations made were changes specific to mitochondrial structure both outside and within the MacTel zone in all retinal cell types, with the exception of those in the retinal pigment epithelium (RPE). The lesion areas, which are a hallmark of MacTel, extend from Bruch's membrane and the choriocapillaris, through all depths of the retina, and include cells from the RPE, retinal vascular elements, and extensive hypertrophic basement membrane material. Where the Müller glial cells are lost, we have identified a significant population of microglial cells, exclusively within the Henle fiber layer, which appear to ensheathe the Henle fibers, similar to that seen normally by Müller cells.</p><p><strong>Discussion: </strong>Since Müller cells synthesize retinal serine, whereas retinal neurons do not, we propose that serine deficiency, required for normal mitochondrial function, may relate to mitochondrial changes that underlie the development of MacTel. With mitochondrial changes occurring retina-wide, the question remains as to why the Müller cells are uniquely susceptible within the MacTel zone.</p>","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal vascular reactivity in carriers of X-linked inherited retinal disease – a study using optical coherence tomography angiography","authors":"S. Gocuk, X. Hadoux, Charmaine Catipon, Elise Cichello, Himeesh Kumar, J. Jolly, Peter van Wijngaarden, Thomas Llewelyn Edwards, L. Ayton, David Cordeiro Sousa","doi":"10.3389/fopht.2024.1415393","DOIUrl":"https://doi.org/10.3389/fopht.2024.1415393","url":null,"abstract":"Female carriers of X-linked inherited retinal diseases (IRDs) can show highly variable phenotypes and disease progression. Vascular reactivity, a potential disease biomarker, has not been investigated in female IRD carriers. In this study, functional optical coherence tomography angiography (OCT-A) was used to dynamically assess the retinal microvasculature of X-linked IRD carriers.Genetically confirmed female carriers of IRDs (choroideremia or X-linked retinitis pigmentosa), and healthy women were recruited. Macular angiograms (3x3mm, Zeiss Plex Elite 9000) were obtained in 36 eyes of 15 X-linked IRD female carriers and 21 age-matched control women. Two tests were applied to test vascular reactivity: (i) mild hypoxia and (ii) handgrip test, to induce a vasodilatory or vasoconstrictive response, respectively. Changes to vessel density (VD) and vessel length density (VLD) were independently evaluated during each of the tests for both the superficial and deep capillary plexuses.In the control group, the superficial and deep VD decreased during the handgrip test (p<0.001 and p=0.037, respectively). Mean superficial VLD also decreased during the handgrip test (p=0.025), while the deep plexus did not change significantly (p=0.108). During hypoxia, VD and VLD increased in the deep plexus (p=0.027 and p=0.052, respectively) but not in the superficial plexus. In carriers, the physiologic vascular responses seen in controls were not observed in either plexus during either test, with no difference in VD or VLD noted (all p>0.05).Functional OCT-A is a useful tool to assess dynamic retinal microvascular changes. Subclinical impairment of the physiological vascular responses seen in carriers of X-linked IRDs may serve as a valuable clinical biomarker.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141663324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of rh-NGF in the management of neurotrophic keratopathy","authors":"Anna M Roszkowska, R. Spinella, Alessandro Calderone, Marianna Sindoni, Bogumił H. Wowra, Maciej Kozak, Katarzyna Sajak-Hydzik, Jorge Aliò","doi":"10.3389/fopht.2024.1408587","DOIUrl":"https://doi.org/10.3389/fopht.2024.1408587","url":null,"abstract":"Neurotrophic keratitis or keratopathy (NK) is a degenerative corneal disease induced by impairment of the trigeminal nerve function. This condition may lead to persistent epithelial defects, corneal ulceration, and perforation. The diagnosis of NK requires a careful investigation of any ocular and systemic condition associated with the disease and ocular surface and corneal sensitivity examinations. In the past, several medical and surgical procedures were used to treat this condition with different clinical effectiveness. Cenegermin is a recombinant human nerve growth factor (rh-NGF) that supports corneal reinnervation. Different clinical trials have demonstrated the safety and efficacy of topical cenegermin in patients with moderate to severe neurotrophic keratitis. In this review, we report the literature on clinical results regarding the treatment of NK with cenegermin since its approval by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in 2017 and 2018, respectively.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141670126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updates on protein-prenylation and associated inherited retinopathies","authors":"Sudhat Ashok, Sriganesh Ramachandra Rao","doi":"10.3389/fopht.2024.1410874","DOIUrl":"https://doi.org/10.3389/fopht.2024.1410874","url":null,"abstract":"Membrane-anchored proteins play critical roles in cell signaling, cellular architecture, and membrane biology. Hydrophilic proteins are post-translationally modified by a diverse range of lipid molecules such as phospholipids, glycosylphosphatidylinositol, and isoprenes, which allows their partition and anchorage to the cell membrane. In this review article, we discuss the biochemical basis of isoprenoid synthesis, the mechanisms of isoprene conjugation to proteins, and the functions of prenylated proteins in the neural retina. Recent discovery of novel prenyltransferases, prenylated protein chaperones, non-canonical prenylation-target motifs, and reversible prenylation is expected to increase the number of inherited systemic and blinding diseases with aberrant protein prenylation. Recent important investigations have also demonstrated the role of several unexpected regulators (such as protein charge, sequence/protein-chaperone interaction, light exposure history) in the photoreceptor trafficking of prenylated proteins. Technical advances in the investigation of the prenylated proteome and its application in vision research are discussed. Clinical updates and technical insights into known and putative prenylation-associated retinopathies are provided herein. Characterization of non-canonical prenylation mechanisms in the retina and retina-specific prenylated proteome is fundamental to the understanding of the pathogenesis of protein prenylation-associated inherited blinding disorders.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141678910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of limbal stem cell deficiency at an academic referral center over a two-year period.","authors":"Jason S Goldberg, Daniel J Fraser, Joshua H Hou","doi":"10.3389/fopht.2024.1392106","DOIUrl":"10.3389/fopht.2024.1392106","url":null,"abstract":"<p><strong>Aim: </strong>To evaluate the prevalence and clinical characteristics of limbal stem cell deficiency (LSCD) in the setting of a tertiary referral cornea practice at an academic center.</p><p><strong>Patient and methods: </strong>A retrospective chart review was performed to identify all unique medical record numbers (MRNs) presenting to a single cornea specialist (JHH) at the University of Minnesota during calendar years 2019 and 2020. Records were queried and confirmed for a diagnosis of LSCD. Clinical characteristics of identified patients, including demographics, etiology of LSCD, severity of LSCD, treatment, and best corrected visual acuity (BCVA) at final follow-up, were documented.</p><p><strong>Results: </strong>In total 1436 unique MRNs were identified over the study period. There were 61 individuals (91 eyes) diagnosed with LSCD, resulting in a prevalence of 4.25% (95% CI, 3.33-5.42). Of 91 eyes, 60 eyes were bilateral (65.9%). Among all eyes, ocular surface burns were the most common etiology (18.7%) followed by iatrogenic or medicamentosa (15.4%). There were 51 eyes (56.0%) that underwent some form of transplantation. The median BCVA at final follow-up was Snellen 20/80 (range 20/20 to no light perception).</p><p><strong>Conclusions: </strong>The prevalence of LSCD found at a cornea subspecialty tertiary referral center in our study was much higher than previously reported prevalence rates. This may reflect referral bias and potential underdiagnosis of LSCD in practices outside of subspecialty referral centers. The high prevalence rate in our study also suggests that LSCD patients are concentrated in subspecialty referral practices, with many having high morbidity disease. This constitutes a major health burden for these practices.</p>","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intensity-based optoretinography reveals sub-clinical deficits in cone function in retinitis pigmentosa","authors":"Mina Gaffney, Thomas B. Connor, Robert F. Cooper","doi":"10.3389/fopht.2024.1373549","DOIUrl":"https://doi.org/10.3389/fopht.2024.1373549","url":null,"abstract":"Clinical tools have been widely used in the diagnosis, description, and monitoring the progression of retinitis pigmentosa (RP); however, many of these methods have inherently low sensitivity and specificity, and significant photoreceptor disruption can occur before RP progression has clinically manifest. Adaptive optics scanning light ophthalmoscopy (AOSLO) has shown promise as a powerful tool for assessing photoreceptor disruption both structurally and functionally due to its increased resolution.Here we assess photoreceptor structure and function at the cellular level through AOSLO by acquiring intensity based optoretinography (iORG) in 15 individuals with no reported retinal pathology and 7 individuals with a prior clinical diagnosis of RP. Photoreceptor structure was quantified by calculating cone nearest neighbor distance (NND) across different retinal eccentricities from the AOSLO images. Cone outer segment length was measured across different retinal eccentricities using optical coherence tomography (OCT) derived longitudinal reflectivity profiles (LRPs). Finally, iORG measures of photoreceptor function were compared to retinal sensitivity as measured using the macular integrity assessment (MAIA) microperimeter.Broadly, participants with RP exhibited increasing cone nearest neighbor distances and decreasing cone outer segment length as a function of retinal eccentricity, consistent with prior reports for both controls and individuals with RP. Nearly all individuals with RP had reduced iORG amplitudes for all retinal eccentricities when compared to the control cohort, and the reduction was greater in eccentricities further from the fovea. Comparing iORG amplitudes to MAIA retinal sensitivity, we found that the iORG was more sensitive to early changes in photoreceptor function whereas MAIA was more sensitive to later stages of disease.This highlights the utility of iORG as a method to detect sub-clinical deficits in cone function in all stages of disease progression and supports the future use of iORG for identifying cells that are candidates for cellular based therapies.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial-temporal comparison of Eph/Ephrin gene expression in ocular lenses from aging and knockout mice","authors":"Peter N. Huynh, Catherine Cheng","doi":"10.3389/fopht.2024.1410860","DOIUrl":"https://doi.org/10.3389/fopht.2024.1410860","url":null,"abstract":"Cataracts, defined as any opacity in the transparent ocular lens, remain the leading cause of blindness and visual impairment in the world; however, the etiology of this pathology is not fully understood. Studies in mice and humans have found that the EphA2 receptor and the ephrin-A5 ligand play important roles in maintaining lens homeostasis and transparency. However, due to the diversity of the family of Eph receptors and ephrin ligands and their promiscuous binding, identifying functional interacting partners remains a challenge. Previously, 12 of the 14 Ephs and 8 of 8 ephrins in mice were characterized to be expressed in the mouse lens. To further narrow down possible genes of interest in life-long lens homeostasis, we collected and separated the lens epithelium from the fiber cell mass and isolated RNA from each compartment in samples from young adult and middle-aged mice that were either wild-type, EphA2–/– (knockout), or ephrin-A5–/–. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was implemented to compare transcript levels of 33 Eph and ephrin gene variants in each tissue compartment. Our results show that, of the Eph and ephrin variants screened, 5 of 33 showed age-related changes, and 2 of 33 showed genotype-related changes in lens epithelium. In the isolated fibers, more dynamic gene expression changes were observed, in which 12 of 33 variants showed age-related changes, and 6 of 33 showed genotype-related changes. These data allow for a more informed decision in determining mechanistic leads in Eph-ephrin-mediated signaling in the lens.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141266871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High salt diet alleviates disease severity in native experimental autoimmune uveitis.","authors":"Naomi Derluyn, Vincent Foucart, Marko Verce, Rami Abdo, Louis Vaudoisey, Deborah Lipski, Véronique Flamand, Amandine Everard, Catherine Bruyns, François Willermain","doi":"10.3389/fopht.2024.1370374","DOIUrl":"10.3389/fopht.2024.1370374","url":null,"abstract":"<p><strong>Background: </strong>Recent studies reported a link between high salt diet (HSD) and clinical exacerbation in mouse models of autoimmune diseases, mainly through the induction of pathogenic Th17 cells and/or HSD-induced dysbiosis. However, the topic remains controversial and not fully understood.</p><p><strong>Purpose: </strong>In this study, we investigated the effects of HSD on the development of experimental autoimmune uveitis (EAU) in C57BL/6J mice.</p><p><strong>Methods and results: </strong>Unexpectedly, our data showed a significant attenuating effect of HSD on disease severity of native EAU, induced by direct immunization with IRBP peptide. That said, HSD had no effect on EAU disease severity induced by adoptive transfer of semi-purified auto-reactive IRBP-specific T lymphocytes. Accordingly, HSD did not affect IRBP-specific systemic afferent immune response as attested by no HSD-linked changes in T lymphocytes proliferation, cytokine production and Treg proportion. Gut microbiota analysis from cecal samples in naïve and EAU mice demonstrated that HSD affected differentially α-diversity between groups, whereas β-diversity was significantly modified in all groups. Unknown <i>Tannerellaceae</i> was the only taxon associated to HSD exposure in all treatment groups. Interestingly, a significantly higher abundance of unknown <i>Gastranaerophilales</i>, with potential anti-inflammatory properties, appeared in HSD-fed native EAU mice, only.</p><p><strong>Discussion: </strong>In conclusion, our study suggests a possible impact of HSD on gut microbiota composition and consequently on development and clinical severity of EAU. Further studies are required to investigate the potential beneficial role of <i>Gastranaerophilales</i> in EAU.</p>","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report: Inferior valved for non-valved glaucoma drainage device exchange for glaucoma control and cosmesis.","authors":"Abdullah M Khan, Maram E A Abdalla Elsayed, Rizwan Malik","doi":"10.3389/fopht.2024.1361898","DOIUrl":"10.3389/fopht.2024.1361898","url":null,"abstract":"<p><strong>Introduction: </strong>While the exchange of a superior valved glaucoma drainage device (GDD) for a non-valved GDD has been reported for achieving glaucoma control, inferior GDD exchange for improving the cosmetic appearance of the eyes due to poor appearance caused by encapsulated GDDs has not been previously documented. Here, we report on two patients with inferior valved GDDs who underwent an exchange for non-valved devices for glaucoma control and cosmetic improvement.</p><p><strong>Case description: </strong>We report on the case of a 23-year-old gentleman and that of an 8-year-old girl, both of whom had inferior valved GDDs with uncontrolled intraocular pressure and unsightly appearance due to encapsulated GDD plates within the palpebral aperture. Both patients were unhappy about the appearance of their eyes. In each case, improvements in both glaucoma control and cosmesis were achieved by exchanging the valved GDDs for non-valved ones.</p><p><strong>Conclusion: </strong>Exchanging a valved for a non-valved GDD might help improve the cosmetic appearance of the eyes, in addition to providing glaucoma control.</p>","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}