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  • Prevalence of Maculopathy Associated with Long Term Pentosan Polysulfate Therapy
    Ophthalmology (IF 7.732) Pub Date : 2020-01-17
    Robin A. Vora; Amar P. Patel; Ronald Melles

    A significant number of Kaiser Permanente Northern California patients who had a cumulative exposure to 500 grams or more of pentosan polysulfate sodium (PPS) developed a pigmentary maculopathy.

    更新日期:2020-01-17
  • Brolucizumab: Evolution Through Preclinical and Clinical Studies, and the Implications for the Management of nAMD
    Ophthalmology (IF 7.732) Pub Date : 2020-01-17
    Quan Dong Nguyen; Arup Das; Diana V. Do; Pravin Dugel; Andre Gomes; Frank G. Holz; Adrian Koh; Carolyn Pan; Yasir J. Sepah; Nikhil Patel; Heather MacLeod; Patrik Maurer

    Improving or maintaining visual acuity is the main goal for treatment of neovascular age-related macular degeneration (nAMD). Current nAMD standard of care dictates frequent intravitreal anti-VEGF injections, which places substantial burden on patients, caregivers, and physicians. Brolucizumab, a newly developed anti-VEGF molecule for nAMD treatment, has demonstrated longer durability and improvement in visual and anatomical outcomes in clinical studies in a q12-week regimen, indicating its potential to reduce treatment burden as an important therapeutic tool in nAMD management. This review focuses on the development of brolucizumab and the preclinical and clinical studies evaluating its efficacy, tolerability, and safety. Brolucizumab (also known as RTH258 and ESBA1008), is a humanized, single-chain variable fragment (scFv) antibody with a molecular mass of ∼26kDa that inhibits VEGF-A. Preclinical studies show that brolucizumab readily penetrates the retina to reach the retinal pigment epithelium (RPE)/choroid with minimal subsequent systemic exposure. The safety, tolerability, and efficacy of a single intravitreal brolucizumab administration in patients with treatment-naïve nAMD was first demonstrated in the SEE Phase 1/2 study. The OSPREY Phase 2 study showed brolucizumab to be as efficacious as aflibercept in a q8-week regimen with regard to BCVA and brolucizumab achieving greater fluid resolution. In addition, brolucizumab-treated patients in the OSPREY study were subsequently challenged with a q12-week dosing interval and the outcomes provided key information for the study design and endpoints of the Phase 3 studies. In the HAWK and HARRIER Phase 3 studies, following 3 monthly loading injections, brolucizumab treatment regimen (q12-week or q8-week) was guided by individual disease activity assessment using functional and anatomical parameters (central subfield thickness [CST], intra- or sub-retinal fluid [IRF/SRF]) versus aflibercept (q8-week). Fewer brolucizumab 6 mg-treated eyes had disease activity versus aflibercept, and anatomical outcome results at Weeks 16 and 48 demonstrate brolucizumab as a potent drying agent. Moreover, of patients treated with 6-mg brolucizumab, 55.6% and 51.0% maintained a q12-week dosing interval immediately after the loading phase until Week 48 in HAWK and HARRIER, respectively. These Phase 3 studies demonstrated that brolucizumab q12-week regimen maintains efficacy and safety while reducing treatment burden associated with regular intravitreal injections for patients with nAMD.

    更新日期:2020-01-17
  • Povidone-iodine pharmacokinetics and study design
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-17
    Jagger Koerner; Andrzej Grzybowski

    Dr. Gnanasekaran et al. reported the bactericidal activity of various concentrations of povidone iodine (PI) solution in an agar plate experiment of respiratory flora. The study design and the pharmacokinetic properties of PI solution ensured that dilute PI would not be effective in this study. These results may not replicate the typical clinical situation and are significantly different than a previously reported agar plate experiment, again owing to subtle but very significant differences in methodology.

    更新日期:2020-01-17
  • Preoperative clinical factors and visual outcomes following orbital decompression with dysthyroid optic neuropathy
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-17
    Mizuki Tagami; Shigeru Honda; Atsushi Azumi

    To investigate preoperative clinical factors and visual outcomes of Japanese patients with dysthyroid optic neuropathy (DON) after urgent orbital decompression. This retrospective, observational case series study investigated 44 patients who exhibited several preoperative clinical factors that might be associated with the need for urgent orbital decompression due to DON. Additionally, the visual acuity of DON patients was compared between the patients preoperatively and at 1 and 6 months postoperatively. All 44 patients received steroid and with or without radiation therapy, with 27 patients able to avoid undergoing urgent surgery. However, the remaining 17 patients required urgent orbital decompression following a lack of response to the therapy. None of the patients who initially avoided surgery required additional surgery for DON. Factors significantly associated with the need for urgent orbital decompression surgery included: female gender, older age, long disease duration, unilateral significant DON, history of resistance to pulsed steroid therapy, unstable thyroid function, high TRAb (Thyrotrophin receptor antibody)value, poor visual acuity, presence of central diplopia, and presence of corneal problems (P < 0.05 each). The results also showed that postoperative visual outcomes of surgery for DON were acceptable. This study revealed several preoperative clinical factors for DON that appear to be associated with the need for urgent orbital decompression surgery in Japanese patients.

    更新日期:2020-01-17
  • A proposal of an algorithm for the diagnosis and treatment of recurrence or treatment failure of retinopathy of prematurity after anti-VEGF therapy based on a large case series
    Graefes Arch. Clin. Exp. Ophthalmol. (IF 2.250) Pub Date : 2020-01-17
    Maria A. Martínez-Castellanos, Ana González-H.León, Juan C. Romo-Aguas, Luis A. Gonzalez-Gonzalez

    Abstract Purpose To provide a diagnostic algorithm of recurrence and treatment failure after intravitreal bevacizumab (IVB) injection for retinopathy of prematurity type 1 (ROP1) and the stepwise therapeutic approach for both conditions. Methods Retrospective chart review of all patients diagnosed with ROP1 initially treated with IVB in 6 tertiary referral centers of Toluca and Mexico City from 2005 to 2017. Treatment failure was defined as persistence or progression of neovascularization, elevation of the ridge, worsening of plus disease, or retinal crunch within the first week after treatment. Recurrence was defined as the new appearance of plus disease, an elevated ridge, or pathological new vessels after an initial regression of ROP following treatment. Therapy was observation, switch of anti-VEGF agent, retinal photocoagulation, vitrectomy, or a combination of two or more, depending on the severity of findings. Results A total of 672 patients who received intravitreal bevacizumab injection for ROP1 treatment were included. Of these, 2.5% (17 patients) failed to treatment, 6.8% (46 patients) developed a recurrence for ROP, and 5.5% (37 patients) carried a misdiagnosis of recurrence and were diagnosed with other than ROP1 after examination. Based on the severity of findings, patients with recurrence or treatment failure were further treated by observation, repeat anti-VEGF intravitreal injection (bevacizumab or other), laser photocoagulation, vitrectomy, or a combination of these. Based on the treatment results, a therapeutic algorithm was created. Conclusions Intravitreal injection of anti-VEGFs for the treatment of ROP warrants close follow-up as some of these patients may have treatment failure or recurrence of the disease. It is crucial to differentiate between them to avoid a misdiagnosis and offer the correct treatment. We propose a novel algorithm for the follow-up and treatment approach of ROP1 following initial treatment with IVB. This algorithm offers a summary of our recommendations based on a large case series of ROP1 patients. It is meant to grow and expand as more clinical evidence becomes available.

    更新日期:2020-01-17
  • Correction: Efficacy of toric intraocular lens implantation with high corneal astigmatism within the United Kingdom’s National Health Service
    Eye (IF 2.366) Pub Date : 2020-01-17
    Andrew J. Swampillai; Ali. Khanan Kaabneh; Nabil E. Habib; Catriona Hamer; Phillip J. Buckhurst

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-01-17
  • Circular RNA-ZNF609 regulates corneal neovascularization by acting as a sponge of miR-184
    Exp. Eye Res. (IF 2.998) Pub Date : 2020-01-16
    Pengcheng Wu; Dongyan Zhang; Yuanyuan Geng; Rui Li; Yanan Zhang

    Corneal neovascularization can cause abnormal blood vessels to grow in the normally transparent and translucent cornea leading to various sight-threatening eye diseases. microRNAs and circular RNAs are known to play essential roles in the regulation of numerous biological functions. It is urgently needed to understand the molecular mechanism of miRNAs and circular RNAs in the corneal neovascularization. We aimed to elucidate the role of a specific a circular RNA, cZNF609, in the corneal neovascularization. cZNF609 and miR-184 levels were determined by RT-qPCR. Luciferase reporter assay and RNA immunoprecipitation assay were conducted to verify the target of cZNF609. The biological function of cZNF609 and miR-184 were assessed via cell proliferation, migration, and tube formation assays in vitro as well as the corneal suture model in vivo. The up-regulation of cZNF609 and down-regulation of miR-184 were observed during corneal neovascularization. cZNF609 acted as a miR-184 sponge to block miR-184 activity. Overexpression of miR-184 suppressed HCEKs cell proliferation, migration in vitro, and angiogenesis in vivo. The miR-184-mediated inhibition effect can be rescued through the re-introduction of cZNF609. Mechanically, cZNF609/miR-184 interaction regulated the downstream Akt and VEGF signaling pathway. Intervention of cZNF609 and miR-184 may serve as a potential strategy for pathological corneal neovascularization treatment.

    更新日期:2020-01-16
  • Two-year observation of morphologic and histopathologic changes in the monkey cornea following small incision allogenic lenticule implantation
    Exp. Eye Res. (IF 2.998) Pub Date : 2020-01-16
    Jing Zhao; Rui Liu; Yang Shen; Xiaoyu Zhang; Yu Zhao; Haipeng Xu; Ye Xu; Xingtao Zhou

    Purpose To observe the morphologic and histopathologic changes of femtosecond laser assisted small incision allogenic intrastromal lenticule implantation (AILI) in monkey corneas. Methods 6 healthy adult monkeys were included. One eye of two monkeys and both eyes of one monkey received femtosecond lenticule extraction with a −4.0 diopter (D) correction. Each extracted refractive donor lenticule was immediately allogeneically transplanted into a corneal stromal pocket created by a femtosecond laser in another monkey's eye. A postoperative two-year follow-up was performed with slit lamp microscopy, corneal topography, anterior segment optical coherence tomography and in vivo confocal microscopy. All eyes were enucleated for Hematoxylin-Eosin staining and transmission electron microscopy (TEM) observation. Results No complications were observed in the follow-up period. At postoperative 2 years, the corneas remained clear and the lenticules were integrated with the surrounding tissue under slit lamp microscopy. Nerve fiber regeneration was detected in the lenticule layer as observed through confocal microscopy. Corneal power was increased by 1.83 ± 1.36 D after 2 years, which was less than at 6 months (3.27 ± 1.2 D). Disordered fibers and decreased keratocytes in the implanted lenticules could be detected under light microscopy and TEM, with a clear boundary between the lenticules and the surrounding tissue. Conclusions Small incision AILI is feasible and safe for reshaping the cornea. Corneal healing remained stable while refraction showed a moderate regression within postoperative 2 years.

    更新日期:2020-01-16
  • Ex vivo anti-microbial efficacy of various formaldehyde releasers against antibiotic resistant and antibiotic sensitive microorganisms involved in infectious keratitis
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-15
    Daeryl E. Amponin; Joanna Przybek-Skrzypecka; Mariya Zyablitskaya; Anna Takaoka; Leejee H. Suh; Takayuki Nagasaki; Stephen L. Trokel; David C. Paik

    Corneal infections with antibiotic-resistant microorganisms are an increasingly difficult management challenge and chemically or photochemically cross-linking the cornea for therapy presents a unique approach to managing such infections since both direct microbial pathogens killing and matrix stabilization can occur simultaneously. The present study was undertaken in order to compare the anti-microbial efficacy, in vitro, of 5 candidate cross-linking solutions against 5 different microbial pathogens with relevance to infectious keratitis. In vitro bactericidal efficacy studies were carried out using 5 different FARs [diazolidinyl urea (DAU), 1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione (DMDM), sodium hydroxymethylglycinate (SMG), 2-(hydroxymethyl)-2-nitro-1,3-propanediol (NT = nitrotriol), 2-nitro-1-propanol (NP)] against 5 different microbial pathogens including two antibiotic-resistant species [methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Pseudomonas aeruginosa (PA), and Candida albicans (CA)]. Standard in vitro antimicrobial testing methods were used. The results for MSSA were similar to those for MRSA. DAU, DMDM, and SMG all showed effectiveness with greater effects generally observed with longer incubation times and higher concentrations. Against MRSA, 40 mM SMG at 120 min showed a > 95% kill rate, p < 0.02. Against VRE, 40 mM DAU for 120 min showed a > 94% kill rate, p < 0.001. All FARs showed bactericidal effect against Pseudomonas aeruginosa, making PA the most susceptible of the strains tested. Candida showed relative resistance to these compounds, requiring high concentrations (100 mM) to achieve kill rates greater than 50%. Our results show that each FAR compound has different effects against different cultures. Our antimicrobial armamentarium could potentially be broadened by DAU, DMDM, SMG and other FARs for antibiotic-resistant keratitis. Further testing in live animal models are indicated.

    更新日期:2020-01-15
  • Correction: Lamellar hole-associated epiretinal membrane is a common featureof macular holes in retinitis pigmentosa
    Eye (IF 2.366) Pub Date : 2020-01-15
    Jingjing Liu; Jiao Lyu; Xiang Zhang; Peiquan Zhao

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-01-15
  • Small incision lenticule extraction for the correction of myopia with astigmatism: outcomes of the US Food and Drug administration premarket approval clinical trial
    Ophthalmology (IF 7.732) Pub Date : 2020-01-15
    Jon G. Dishler; Stephen Slade; Stefanie Seifert; Steven C. Schallhorn

    Objective To present outcomes of the US food and drug administration premarket approval clinical trial of the small incision lenticule extraction (SMILE) for the correction of myopia and astigmatism. Design Prospective multi-center clinical trial Subjects The study included 357 eyes of 357 patients treated with SMILE (50 for myopia and 307 for myopia with astigmatism). Preoperative sphere ranged between -1.00 and -10.00 D, with the manifest spherical equivalent (MSE) up to -11.50 D and the refractive cylinder up to -3.00 D. Methods Subjects were followed for 12 months. Corrected (CDVA) and uncorrected (UDVA) visual acuity, stability of the manifest refraction and vector analysis of refractive cylinder are presented for the 307 eyes treated for myopia with astigmatism. Adverse events are presented for all 357 eyes. Results Of the 307 astigmatic eyes enrolled in the study, 304 were successfully treated. In three eyes, the procedure was aborted due to intraoperative suction loss. The mean MSE reduced from -5.39 ± 2.30D at baseline to -0.01 ± 0.24D at 12 months. Of all eyes, 95.3% were within 0.50D of emmetropia at 12 months. The percentage of eyes with UDVA 20/20 or better was 89.0%. There was no loss of 2 or more lines of CDVA at the 12-month visit. The refractive cylinder reduced from -1.53 ± 0.70D at baseline to -0.18 ± 0.31D at 12 months. The mean correction ratio (CR) of refractive cylinder was 0.96 ± 0.16, but there was a slight undercorrection apparent for higher attempted corrections of astigmatism. There were 3 intraoperative adverse events associated with difficult lenticule removal and resultant cap tear and all resolved without sequelae at postoperative day 1. During the postoperative period, 8 adverse events were recorded, but none of them had significant consequences. Conclusion SMILE for the treatment of myopia and astigmatism was safe and effective and the reported adverse events had no significant impact on visual acuity. Slight undercorrection of refractive cylinder requires further attention.

    更新日期:2020-01-15
  • A review on the epidemiology of myopia in school children worldwide
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-14
    Andrzej Grzybowski; Piotr Kanclerz; Kazuo Tsubota; Carla Lanca; Seang-Mei Saw

    Due to high prevalence myopia has gained importance in epidemiological studies. Children with early onset are at particular risk of complications associated with myopia, as progression over time might result in high myopia and myopic macular degeneration. Both genetic and environmental factors play a role in the increasing prevalence of myopia. The aim of this study is to review the current literature on epidemiology and risk factors for myopia in school children (aged 6–19 years) around the world. PubMed and Medline were searched for the following keywords: prevalence, incidence, myopia, refractive error, risk factors, children and visual impairment. English language articles published between Jan 2013 and Mar 2019 were included in the study. Studies were critically reviewed for study methodology and robustness of data. Eighty studies were included in this literature review. Myopia prevalence remains higher in Asia (60%) compared with Europe (40%) using cycloplegic refraction examinations. Studies reporting on non-cycloplegic measurements show exceptionally high myopia prevalence rates in school children in East Asia (73%), and high rates in North America (42%). Low prevalence under 10% was described in African and South American children. In recent studies, risk factors for myopia in schoolchildren included low outdoor time and near work, dim light exposure, the use of LED lamps for homework, low sleeping hours, reading distance less than 25 cm and living in an urban environment. Low levels of outdoor activity and near work are well-established risk factors for myopia; this review provides evidence on additional environmental risk factors. New epidemiological studies should be carried out on implementation of public health strategies to tackle and avoid myopia. As the myopia prevalence rates in non-cycloplegic studies are overestimated, we recommend considering only cycloplegic measurements.

    更新日期:2020-01-15
  • 10_3928_1081597X_20191211_02
    J. Refract. Surg. (IF 3.000) Pub Date : 2020-01-13
    Colin Chan, Michael Lawless, Gerard Sutton, Chris Hodge

    Improvement in vision-related quality of life has been consistently reported following corneal laser refractive surgery.1–3 These benefits appear to continue long-term unless a patient experiences a reduction in uncorrected vision.4,5 Refractive regression, the leading cause of loss of uncorrected visual acuity, will occur in a minority of patients following laser surgery.6 The incidence will vary based on preoperative risk factors and surgical technique, with studies indicating regression rates as low as 0.48% in a large cohort of patients under the care of experienced surgeons to as high as

    更新日期:2020-01-15
  • 10_3928_1081597X_20191210_01
    J. Refract. Surg. (IF 3.000) Pub Date : 2020-01-13
    Avi Wallerstein, Mathieu Gauvin, Mark Cohen

    We read with interest “Comparison of Wavefront-Optimized Ablation and Topography-Guided Contoura Ablation With LYRA Protocol in LASIK” by Ozulken et al.1 Eyes with 0.75 diopters or greater magnitude difference between clinically measured manifest refractive astigmatism and Contoura-measured anterior corneal astigmatism (ACA) and 10° or less axis difference received Contoura treatment (WaveLight Contoura; Alcon Laboratories, Inc., Fort Worth, TX), whereas contralateral eyes without these criteria were excluded from Contoura treatment and received wavefront-optimized (WFO) treatment. This

    更新日期:2020-01-15
  • 10_3928_1081597X_20191119_02
    J. Refract. Surg. (IF 3.000) Pub Date : 2020-01-13
    Di Chen, Ge Cui, Xuejiao Wang, Ying Li, Yan Luo

    Implantation of the posterior chamber phakic Visian Implantable Collamer Lens (ICL) (STAAR Surgical AG, Nidau, Switzerland) has been proved to be an effective and predictable method of correcting high myopia.1–3 Numerous studies have proved its safety, and the incidence of moderate and severe complications is low.4–8 However, complications (eg, postoperative intraocular pressure [IOP] increase, endothelial cell loss, and inflammation) have been reported and may cause long-term safety concerns.2,9 Since the emergence of ophthalmic viscosurgical device (OVD) in the 1980s, endothelial cell

    更新日期:2020-01-15
  • 10_3928_1081597X_20191203_01
    J. Refract. Surg. (IF 3.000) Pub Date : 2020-01-13
    Renan F Oliveira, Gabriel A Ferreira, Vinícius C Ghanem, Paulo Elias Corrêa-Dantas, Ramon C Ghanem

    Epidemic keratoconjunctivitis is a contagious adenoviral infection that is considered the most common ocular infectious disease.1–4 Subepithelial infiltrates may present within the second or third week of epidemic keratoconjunctivitis as multifocal, elevated, nummular opacities with inflammatory infiltrate in the anterior stroma. They are frequently associated with photophobia, conjunctival hyperemia, and ocular discomfort. Topical treatment with low-dose steroids, cyclosporin A 1%, or tacrolimus 0.03% reduces infiltrates and their associated symptoms in most cases, although they frequently

    更新日期:2020-01-15
  • 10_3928_1081597X_20191211_01
    J. Refract. Surg. (IF 3.000) Pub Date : 2020-01-13
    Emilio A Torres-Netto, Bogdan Spiru, Sabine Kling, Francesca Gilardoni, Apostolos Lazaridis, Walter Sekundo, Farhad Hafezi

    Albeit rare, iatrogenic postoperative ectasia represents a major complication after laser visual correction.1 Although the evaluation of topography, tomography, epithelial thickness mapping, and corneal biomechanical properties have increased our ability to preoperatively detect corneal susceptibility,2,3 ectasia is occasionally being reported after corneal refractive laser surgeries. With the recent emergence and successful implementation of the femtosecond laser, several advances have emerged in refractive surgery. In 2011, the small incision lenticule extraction (SMILE) technique was

    更新日期:2020-01-15
  • 10_3928_1081597X_20191114_01
    J. Refract. Surg. (IF 3.000) Pub Date : 2020-01-13
    Robert Edward Ang

    The small-aperture intraocular lens (IOL) (IC-8 IOL; AcuFocus, Irvine, CA) is a one-piece, hydrophobic acrylic, posterior chamber monofocal IOL that provides increased range of vision from far to near, by extending the depth of focus.1,2 It works by eliminating the unfocused peripheral light rays while the central rays pass unaffected and focus on the retina.3 Reducing the size of the blur circle from unfocused peripheral light improves the image resolution for intermediate and near vision, with minimal to no change to distance vision. The IC-8 IOL is indicated for contralateral implantation

    更新日期:2020-01-15
  • 10_3928_1081597X_20191223_01
    J. Refract. Surg. (IF 3.000) Pub Date : 2020-01-13
    TBD

    The article “Evaluation of Corneal Changes After Conventional Versus Accelerated Corneal Cross-linking: A Randomized Controlled Trial” by Hashemian et al., which was published in the December 2014 issue of the Journal of Refractive Surgery (volume 30, number 12, pp. 837–842), has been amended to include a factual correction. An error was identified subsequent to its original printing. In the Patients and Methods section, the sentence “In the accelerated group, irradiation was performed using 3 minutes of UVA 365-µm light with 30 mW/cm2 (5.4 J/cm2 dose in each group) irradiance” should be “In

    更新日期:2020-01-15
  • 10_3928_1081597X_20191114_02
    J. Refract. Surg. (IF 3.000) Pub Date : 2020-01-13
    Shengbei Weng, Daoman Xiang, Limian Lin, Haiqin Lin, Fang Liu, Quan Liu

    Small incision lenticule extraction (SMILE), which is a flapless surgical technique for the correction of refractive errors, has been performed in a large number of cases.1,2 It has advantages over laser in situ keratomileusis (LASIK) in terms of dry eye in the early postoperative period.3,4 However, it has been postulated that a longer period of time is required for visual recovery after SMILE in comparison with LASIK.5,6 Moreover, recent research has confirmed that visual outcomes of SMILE for myopia were worse compared with femtosecond laser–assisted LASIK within 24 hours postoperatively.7

    更新日期:2020-01-15
  • 10_3928_1081597X_20191217_02
    J. Refract. Surg. (IF 3.000) Pub Date : 2020-01-13
    Chenghua Wei, E Song, Lixin Mei

    We read with great interest the article by Brenner et al.1 in the February 2019 issue regarding early surface ablation on aborted laser in situ keratomileusis (LASIK) flaps. In femtosecond laser–assisted LASIK, the procedure was occasionally aborted due to various abnormal events that lead to complicated flaps. The rescue method reported in this article was photorefractive keratectomy or laser epithelial keratomileusis. These operations require a mechanical method to remove the corneal epithelium. However, in some cases with side cutting or lifting of the flap, the corneal flap did not adhere

    更新日期:2020-01-15
  • 10_3928_1081597X_20191204_01
    J. Refract. Surg. (IF 3.000) Pub Date : 2020-01-13
    Karen L Christopher, D Claire Miller, Jennifer L Patnaik, Anne M Lynch, Richard S Davidson, Michael J Taravella

    Extended depth of focus intraocular lenses (EDOF IOLs) are becoming an increasingly popular technique to support spectacle independence following cataract surgery. However, patients report glare, halos, and starbursts at a much higher rate with EDOF IOLs than with monofocal lenses.1,2 For patients with previous laser refractive surgery (laser-assisted in situ keratomileusis [LASIK] or photorefractive keratectomy [PRK]) who are already known to have corneas with above average higher order aberrations and dysphotopsias,3–7 the combination of their previously ablated cornea with an EDOF IOL

    更新日期:2020-01-15
  • 10_3928_1081597X_20191119_01
    J. Refract. Surg. (IF 3.000) Pub Date : 2020-01-13
    Timur M Yildirim, Grzegorz Labuz, Ramin Khoramnia, Hyeck Soo Son, Sonja K Schickhardt, Ingo Lieberwirth, Michael C Knorz, Gerd U Auffarth

    Current multifocal intraocular lenses (IOLs) use diffractive or refractive optics to allocate the incoming light to two or three focal points or to create an elongated focus offering a greater number of patients spectacle independence than with monofocal IOLs. As a downside, patients with multifocal IOLs may suffer from unwanted visual symptoms, such as glare, halo, or decreased contrast sensitivity.1 Optical simulations have shown that angular zone designs offer better multifocal performance compared to radial zone designs.2 Among the bifocal IOLs, the Lentis MF IOL models (Oculentis GmbH,

    更新日期:2020-01-15
  • 10_3928_1081597X_20191120_01
    J. Refract. Surg. (IF 3.000) Pub Date : 2020-01-13
    TBD

    Each individual listed has donated time, effort, and thought toward reviewing manuscripts written by his or her colleagues. This is a labor of personal and academic dedication, as reviewers receive no pay or recognition for their efforts—except this simple listing. The peer-review process is an essential element in the veracity of papers published in the Journal of Refractive Surgery, an element that cannot be avoided, truncated, or subverted. The reviewers' comments help guide the editors in selecting articles for publication; we emphasize that it is the editors—not the reviewers—who make

    更新日期:2020-01-15
  • Metformin and rapamycin protect cells from vital dye–induced damage in retinal pigment epithelial cells and in vivo
    Graefes Arch. Clin. Exp. Ophthalmol. (IF 2.250) Pub Date : 2020-01-14
    Chih-Wen Shu, Chui-Lien Tsen, Meng-Syuan Li, Youn-Shen Bee, Shi-Han Lin, Shwu-Jiuan Sheu

    Abstract Purpose To evaluate the effect of autophagy inducers on damage caused by vital dye in adult human RPE (ARPE) cells and in a rat model. Methods ARPE-19 cells were exposed to ICG or BBG (0.05 mg/ml) with rapamycin (200 nM) or metformin (2 mM) for 30 min and treated with or without 20 μM chloroquine (CQ) to identify the protein levels of LC3 and SQSTM1 by immunoblotting. In vivo study was performed by injecting 10 μl 0.05% ICG and 0.25% BBG into the subretinal space of the rat eyes, and/or co-treated them with metformin and rapamycin. The retinas were used to determine autophagy with the LC3-II level and apoptosis with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) assay. Results In this study, both ICG and BBG inhibited autophagy flux in adult human retinal pigment epithelium cells (ARPE-19), whereas only ICG consistently reduced autophagy in the retina of rats. Moreover, rapamycin and metformin induced autophagic flux in ARPE-19 cells and increased the LC3-II level in retinal tissues exposed to vital dyes. Both ICG and BBG increased apoptosis in the retina of rats. However, both rapamycin and metformin induced autophagy and reduced the apoptosis caused by vital dyes. Conclusion Taken together, these results suggest that rapamycin and metformin may diminish vital dye–induced retinal damage in vivo through activation of autophagy.

    更新日期:2020-01-14
  • Multi-label classification of retinal lesions in diabetic retinopathy for automatic analysis of fundus fluorescein angiography based on deep learning
    Graefes Arch. Clin. Exp. Ophthalmol. (IF 2.250) Pub Date : 2020-01-14
    Xiangji Pan, Kai Jin, Jing Cao, Zhifang Liu, Jian Wu, Kun You, Yifei Lu, Yufeng Xu, Zhaoan Su, Jiekai Jiang, Ke Yao, Juan Ye

    Abstract Purpose To automatically detect and classify the lesions of diabetic retinopathy (DR) in fundus fluorescein angiography (FFA) images using deep learning algorithm through comparing 3 convolutional neural networks (CNNs). Methods A total of 4067 FFA images from Eye Center at the Second Affiliated Hospital of Zhejiang University School of Medicine were annotated with 4 kinds of lesions of DR, including non-perfusion regions (NP), microaneurysms, leakages, and laser scars. Three CNNs including DenseNet, ResNet50, and VGG16 were trained to achieve multi-label classification, which means the algorithms could identify 4 retinal lesions above at the same time. Results The area under the curve (AUC) of DenseNet reached 0.8703, 0.9435, 0.9647, and 0.9653 for detecting NP, microaneurysms, leakages, and laser scars, respectively. For ResNet50, AUC was 0.8140 for NP, 0.9097 for microaneurysms, 0.9585 for leakages, and 0.9115 for laser scars. And for VGG16, AUC was 0.7125 for NP, 0.5569 for microaneurysms, 0.9177 for leakages, and 0.8537 for laser scars. Conclusions Experimental results demonstrate that DenseNet is a suitable model to automatically detect and distinguish retinal lesions in the FFA images with multi-label classification, which lies the foundation of automatic analysis for FFA images and comprehensive diagnosis and treatment decision-making for DR.

    更新日期:2020-01-14
  • The stability of horizontal ocular alignment of triad exotropia after one-step triple surgery
    Graefes Arch. Clin. Exp. Ophthalmol. (IF 2.250) Pub Date : 2020-01-14
    Lianqun Wu, Weiyi Xia, Lei Li, Sida Xi, Xiying Wang, Wen Wen, Chao Jiang, Guohua Liu, Chen Zhao

    A-pattern exotropia, superior oblique muscle overaction, and dissociated vertical deviation may coexist and are referred to as triad exotropia. The present study evaluated the postoperative stability of horizontal ocular alignment of triad exotropia and possible prognostic factors.

    更新日期:2020-01-14
  • Peripheral retinal neovascularization secondary to highly myopic superficial Retinoschisis: a case report
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-13
    Mingyue Luo; Hong Du; Hua Ding; Rongping Dai

    Peripheral Retinal neovascularization is well-described as a complication of X-linked retinoschisis, but less often observed in myopic and primary retinoschisis. We present a case of a myopic female who developed retinal microvascular abnormalities due to retinoschisis and subsequent vitreous hemorrhage which would cause severe visual damage without timely and proper treatment. A 38-year-old highly myopic Chinese female complained of blurred vision in her right eye. Her best corrected visual acuitiy was 20/20 OU, and her refraction was − 9.00S OU. Dilated fundus examination revealed mild vitreous hemorrhage and abnormal vascular network nasal to the optic disc in her right eye. Optical Coherence Tomography (OCT)- angiography (OCTA) B-Scan showed superficial retinoschisis and well-depicted abnormal retinal microvascular network in inner retinal layer. Sectoral scatter laser photocoagulation was administered. Regression of most abnormal vessels was achieved in 1 month, but the patient experienced an unexpected episode of vitreous hemorrhage 3 months after the initial treatment, which was absorbed spontaneously in 2 weeks. Supplemental laser photocoagulation was applied and regular follow-up visit was suggested. Superficial retinoschisis in pathological myopia can be a driver of retinal microvascular abnormalities, possibly neovascularization, an extremely rare but severe complication which can be vision-threatening without timely and proper intervention.

    更新日期:2020-01-14
  • Prevalence and associated risk factors of dry eye disease in 16 northern West bank towns in Palestine: a cross-sectional study
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-13
    Yousef Shanti; Reham Shehada; May M. Bakkar; Jamal Qaddumi

    Dry Eye Disease (DED) is a multifactorial disease of the interpalpebral ocular surface and tear film that leads to discomfort, fatigue and disturbance in vision. DED affects patients’ quality of life and leads eventually to decrease of productivity. Moreover, it has a considerable socioeconomic burden. It is a growing underdiagnosed health issue and the possible associated risk factors are very common and keep growing worldwide. To assess the prevalence of DED and potential associated risk factors in the Northern West Bank of Palestine. A cross sectional study was conducted in 16 selected towns in Northern West Bank governorates during December 2016 to September 2017. An interviewer-assisted Ocular Surface Disease Index (OSDI) questionnaire was used to study DED symptoms in the study population. Further evaluation of clinical signs of DED was performed using the following objective tests: tear film break-up time (TBUT), fluorescein corneal staining (FL/S) and Schirmer test. Subjects with an OSDI score of 13 or above were considered symptomatic of DED, and DED was defined if an OSDI score ≥ 13 is accompanied by at least one of the following signs in the worse eye: TBUT ≤10 s, Schirmer score ≤ 5 mm and fluorescein corneal staining ≥ grade 1. Seven hundred sixty-nine subjects were recruited from the general non-clinical population in the West Bank. The mean age of participants was 43.61 ± 18.57 years ranging from 18 to 90 years. Females constitute 52.7% of the study population. Based on the diagnostic criteria, the prevalence of DED was 64% (95% confidence interval 60.6–67.3). DED was significantly associated with female gender p = (0.001) and older age p = (0.001). The prevalence of DED is high in the study population. Older age and female gender were associated risk factors with the development of DED.

    更新日期:2020-01-14
  • Clinical outcomes and aetiology of fourth cranial nerve palsy with acute vertical diplopia in adults
    Eye (IF 2.366) Pub Date : 2020-01-13
    Shin Yeop Oh; Sei Yeul Oh

    Background We investigated the clinical outcomes of fourth cranial nerve (CN4) palsy with acute vertical diplopia in adults. Methods A total of 80 patients with acute CN4 palsy who underwent at least 3 months of follow-up were included in this study. We retrospectively investigated the aetiology, rate of recovery, and factors associated with recovery between March 2016 and January 2019. Results The average age of patients with CN4 palsy was about 60 years, and the duration of recovery was 1.5 months: 48 (60.0%) patients had a vascular aetiology and 17 (21.3%) patients had a trauma history. Brain lesions were found in four (5.0%) patients and decompensated cause accounted for four (5.0%) cases. Among the total of 80 patients, 13 (16.3%) failed to completely recover. Non-isolated CN4 palsy with other cranial nerve palsies were recorded in seven cases. The comparison between recovery and non-recovery groups showed that initial deviation angle, aetiology, fundus extorsion, and head tilt status were significantly different factors. Conclusion The recovery rate of acute CN4 palsy was about 80% and duration of recovery was 1.5 months. However, the varying rates and duration of recovery was presented according to aetiology thus we should consider the prognosis by aetiology.

    更新日期:2020-01-14
  • Vitrectomy + 360° cyclopexy with transscleral 810 nm laser application: a novel surgical technique for hypotonic maculopathy
    Eye (IF 2.366) Pub Date : 2020-01-13
    Geovanni Ríos-Nequis; Ingrid Yazmín Pita-Ortiz; Gian Franco Diez-Cattini; Erick Omar Flores-Villalobos; Juan Abel Ramírez-Estudillo; Arthur Levine-Berebichez
    更新日期:2020-01-14
  • Accuracy of IOL power calculations in the very elderly
    Eye (IF 2.366) Pub Date : 2020-01-13
    Ruti Sella; Linda Chou; Alexander K. Schuster; Helena E. Gali; Robert N. Weinreb; Natalie A. Afshari
    更新日期:2020-01-14
  • Requirement for the collagen receptor Endo180 in collagen gel contraction mediated by corneal fibroblasts
    Exp. Eye Res. (IF 2.998) Pub Date : 2020-01-11
    Koichi Nishida; Koji Sugioka; Junko Murakami; Aya Kodama-Takahashi; Isamu Nanri; Hiroshi Mishima; Teruo Nishida; Shunji Kusaka

    The interaction of keratocytes with extracellular matrix components plays an important role in the maintenance of corneal transparency and shape as well as in the healing of corneal wounds. In particular, the interaction of these cells with collagen and cell-mediated collagen contraction contribute to wound closure. Endo180 is a receptor for collagen that mediates its cellular internalization. We have now examined the role of Endo180 in collagen contraction mediated by corneal fibroblasts (activated keratocytes). Antibodies to Endo180 inhibited the contractile activity of mouse corneal fibroblasts embedded in a three-dimensional collagen gel and cultured in the presence of serum, with this effect being both concentration and time dependent and essentially complete at an antibody concentration of 0.2 μg/ml. Whereas corneal fibroblasts cultured in a collagen gel manifested a flattened morphology with prominent stress fibers under control conditions, they showed a spindlelike shape with few stress fibers in the presence of antibodies to Endo180. Antibodies to Endo180 had no effect on the expression of α–smooth muscle actin or the extent of collagen degradation in collagen gel cultures of corneal fibroblasts. Immunohistofluorescence analysis did not detect the expression of Endo180 in the unwounded mouse cornea. However, Endo180 expression was detected in keratocytes migrating into the wound area at 3 days after a corneal incisional injury. Together, our results suggest that Endo180 is required for the contraction of collagen matrix mediated by corneal fibroblasts and that its expression in these cells may contribute to the healing of corneal stromal wounds.

    更新日期:2020-01-13
  • Ganglion Cell Complex Thickness and Macula Vessel Density Loss in Primary Open Angle Glaucoma
    Ophthalmology (IF 7.732) Pub Date : 2020-01-13
    Huiyuan Hou; Sasan Moghimi; James A. Proudfoot; Elham Ghahari; Rafaella C. Penteado; Christopher Bowd; Diya Yang; Robert N. Weinreb

    Purpose To characterize the rate of change of ganglion cell complex(GCC) thickness and macula vessel density in healthy, pre-perimetric glaucoma and primary open angle glaucoma(POAG) eyes. Design Prospective, longitudinal study. Participants 139 eyes(23 healthy eyes, 36 pre-perimetric glaucoma eyes, and 80 POAG eyes) of 94 patients who had at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was 2.0 years for healthy eyes, 2.6 years for pre-perimetric glaucoma eyes, and 2.6 years for POAG eyes. Methods Optical coherence tomography angiography(OCT-A)-based vessel density and OCT-based structural thickness of the same 3×3 mm2 GCC scan slab were evaluated at each visit. The dynamic range-based normalized rates of vessel density and thickness change were calculated and compared within each diagnostic group. The association between the rates of thickness and vessel density change and potential factors, including severity of disease and intraocular pressure(IOP), were evaluated. Main Outcome Measures The rates of GCC thinning and macula vessel density loss. Results Significant rates of both whole image GCC thinning and macula vessel density decrease were detectable in all diagnostic groups(all P<0.05). In healthy eyes and pre-perimetric glaucoma eyes, the normalized rates of GCC thinning and macula vessel density decrease were comparable(all P>0.1). In contrast, the normalized rate(mean,95% CI) of macula vessel density decrease in the POAG eyes(-7.12(-8.36,-5.88)%/year) was significantly faster than GCC thinning(-2.13(-3.35,-0.90)%/year,P<0.001). In the POAG group, more than two-thirds of the eyes showed faster macula vessel density decrease than GCC thinning; faster macula vessel density decrease rate was significantly associated with worse glaucoma severity(P=0.037). The association between GCC thinning rate and glaucoma severity was not significant(P=0.586). IOP during follow-up significantly affected the rate of GCC thinning in all groups(all P<0.05), but had no association with the rate of macula vessel density decrease. Conclusions Both GCC thinning and macula vessel density decrease were detectable over time in all 3 diagnostic groups. In POAG eyes, macula vessel density decrease was faster than GCC thinning and associated with severity of disease. Macula vessel density is useful for evaluating glaucoma progression, particularly in more advanced disease.

    更新日期:2020-01-13
  • Collaborative Ocular Tuberculosis Study (COTS) Consensus Guidelines on the Management of Tubercular Uveitis – Report 1: Guidelines for Initiating Anti-Tubercular Therapy in Tubercular Choroiditis
    Ophthalmology (IF 7.732) Pub Date : 2020-01-11
    Rupesh Agrawal; Ilaria Testi; Sarakshi Mahajan; Yew Sen Yuen; Aniruddha Agarwal; Onn Min Kon; Talin Barisani-Asenbauer; John H. Kempen; Amod Gupta; Douglas A. Jabs; Justine R. Smith; Quan Dong Nguyen; Carlos Pavesio; Vishali Gupta

    Topic An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society (IOIS) and the International Uveitis Study Group (IUSG) systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. Clinical relevance The diagnosis and management of tubercular uveitis pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of anti-tubercular therapy (ATT) in patients with tubercular uveitis. Methods An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, utilizing Oxford levels of medical evidence. In total, 162 statements were identified around when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a two-step modified Delphi process. Results Seventy consensus statements addressed the initiation of ATT in the three subtypes of tubercular choroiditis and in addition 12 consensus statements were developed on the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of any one of the positive immunological tests along with radiological features suggestive of TB. For tubercular serpiginous-like choroiditis and tuberculoma, even one positive immunological test was considered sufficient to recommend ATT even if there are no radiological features suggestive of TB. Conclusions Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion and practical experience, to bridge the gap between clinical need and available medical evidence.

    更新日期:2020-01-13
  • Private Equity in Ophthalmology and Optometry: Analysis of Acquisitions from 2012 to 2019 in the United States
    Ophthalmology (IF 7.732) Pub Date : 2020-01-11
    Evan M. Chen; Jacob T. Cox; Tedi Begaj; Grayson W. Armstrong; Rahul N. Khurana; Ravi Parikh

    Purpose To identify temporal and geographic trends in private equity-backed acquisitions of ophthalmology and optometry practices in the United States. Design A cross-sectional study using private equity acquisition and investment data from January 1, 2012 to October 20, 2019. Participants A total of 228 private equity acquisitions of ophthalmology and optometry practices in the United States between 2012 and 2019. Methods Acquisition and financial investment data were compiled from six financial databases, four industry news outlets and publicly available press releases from private equity firms or platform companies. Main Outcome Measures Yearly trends in ophthalmology and optometry acquisitions including number of total acquisitions, clinical locations and providers of acquired practices as well as subsequent sales, median holding period, geographic footprint and financing status of each platform company. Results A total of 228 practices associated with 1,466 clinical locations and 2,146 ophthalmologists or optometrists were acquired by 29 private equity-backed platform companies. Of these acquisitions, 127, 9, and 92 were comprehensive/multispecialty, retina and optometry practices, respectively. Acquisitions increased rapidly between 2012 and 2019—42 practices were acquired between 2012 and 2016 compared to 186 from 2017 to 2019. Financing rounds of platform companies paralleled temporal acquisition trends. Three platform companies, comprising 60% of platforms formed before 2016, were subsequently sold or recapitalized to new private equity investors by the end of this study period with a median holding period of 3.5 years. In terms of geographic distribution, acquisitions occurred in 40 states with a majority of private equity firms developing multi-state platform companies. New York and California were the two states with the greatest number of PE acquisitions with 22 and 19 respectively. Conclusions Private equity-backed acquisitions of ophthalmology and optometry practices have rapidly increased since 2012, with some platform companies having already been sold or recapitalized to new investors. Private equity-backed platform companies have developed both regionally focused and multi-state models of add-on acquisitions. Future research should assess the impact of private equity investment on patient, provider and practice metrics including health outcomes, expenditures, procedural volume and staff employment.

    更新日期:2020-01-13
  • Effects of radiation therapy on the meibomian glands and dry eye in patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-13
    Sung Eun Kim; Hee Jung Yang; Suk-Woo Yang

    Radiation therapy (RT) is the treatment of choice in patients with low-grade ocular adenexal mucosa-associated lymphoid tissue lymphoma (OAML) and many of them experience post-RT dry eye with varying severity. The purpose of the present study was to investigate ocular effects of RT on meibomian glands and dry eye by directly visualizing structural changes. Secondly, we focused on the comparison of two groups of patients according to tumor location and radiation technique. Sixty-four eyes with OAML of conjunctiva, orbit, lacrimal gland, or lacrimal sac were grouped into conjunctival lymphoma and “orbital-type” lymphoma (i.e., orbit, lacrimal gland, and lacrimal sac). Subjects were investigated for morphological changes in meibomian glands by meiboscore grading system. Radiation technique was examined and Ocular Surface Disease Index (OSDI) questionnaire, Schirmer’s test, tear film break-up time (TBUT), slit lamp examination of corneal surface and lid margin abnormality were conducted before and after RT. The increase in meiboscore was statistically significant over time after RT in both groups (P < 0.001). The extent of increase in meiboscore was significantly greater in the “orbital-type” lymphoma group than in the conjunctival lymphoma group (P < 0.001). The changes in OSDI, TBUT, corneal fluorescein staining score and lid margin abnormality score after RT were significantly different across two groups (P = 0.042, 0.001, 0.035 and 0.001, respectively). Schirmer’s value decreased after RT in both groups. Dry eye symptoms were most severe right after RT in both groups, but a gradual resolution was noted in most patients with conjunctival lymphoma, whereas symptoms persisted in “orbital-type” lymphoma patients. The OSDI score and corneal fluorescein staining score were positively correlated with meiboscore in “orbital-type” patients at post-RT 6 months (r = 0.43, P = 0.04; r = 0.39, P = 0.03, respectively). Patients with OAML had different degrees of morphological changes in meibomian glands according to tumor location and radiation technique. “Orbital-type” lymphoma patients are more likely to experience severe injury to meibomian glands, which eventually leads to persistent dry eye. Patients with “orbital-type” lymphoma should be well informed of post-RT damage on meibomian glands and persistent dry eye.

    更新日期:2020-01-13
  • HCE-T cell line lacks cornea-specific differentiation markers compared to primary limbal epithelial cells and differentiated corneal epithelium
    Graefes Arch. Clin. Exp. Ophthalmol. (IF 2.250) Pub Date : 2020-01-11
    Anna-Klara Rubelowski, Lorenz Latta, Priya Katiyar, Tanja Stachon, Barbara Käsmann-Kellner, Berthold Seitz, Nóra Szentmáry

    Human corneal epithelial cell-transformed (HCE-T) cell line is used as a widely accepted barrier model for pharmacological investigations in the context of eye application. The differentiation of (limbal) corneal epithelial into mature corneal epithelium coincides with the expression of established differentiation markers. If these differentiation mechanisms are disturbed, it will lead to ocular surface disease. In this study, we want to compare the expression of differentiation markers in the HCE-T cell line to differentiated primary epithelial cells (pCECs) and primary limbal epithelial cell (LEC) culture. This is necessary in order to decide whether HCE-T cells could be a tool to study the differentiation process and its regulatory networks in corneal epithelium.

    更新日期:2020-01-13
  • A single Asp isomer substitution in an αA-crystallin-derived peptide induces a large change in peptide properties
    Exp. Eye Res. (IF 2.998) Pub Date : 2020-01-10
    Kosuke Magami; Ingu Kim; Noriko Fujii

    The eye lens is mainly composed of crystallins, which undergo modifications such as oxidation, deamidation and isomerization with aging. Asp58, Asp76, Asp84, and Asp151 residues of αA-crystallin are site-specifically isomerized to L-iso, D-, and D-iso isomers in aged-related cataract lenses. In addition, an αA66–80 peptide, corresponding to the 66–80 (66SDRDKFVIFLDVKHF80) fragment of human αA-crystallin, is detected in aged lens. This peptide induces protein aggregation and causes loss of the chaperone function of α-crystallin. The αA66–80 peptide contains Asp76, but it is not known whether isomerization of Asp76 in αA66–80 specifically induces protein aggregation or affects α-crystallin function. Using Fmoc-based solid-phase synthesis, here we synthesized four αA66–80 peptides, each containing L-, L-iso, D-, or D-isoAsp at position 76, and compared their structures and properties. Normal αA66–80 peptide containing the L-Asp76 isomer increased the EDTA-induced aggregation of ADH protein, DTT-induced aggregation of insulin, and heat-induced aggregation of βL-crystallin. αA66–80 peptide containing D- or D-isoAsp76 had similar or no effects on the aggregation of these proteins. By contrast, αA66–80 peptide containing L-isoAsp76 inhibited the aggregation of all three proteins, indicating that it has chaperone activity. With regard to secondary structure, αA66–80 peptide containing the L-, D-, or D-isoAsp76 isomer had random-coil structure, whereas αA66–80 peptide containing L-isoAsp76 had β-sheet like structure. A Thioflavin T (ThT) assay indicated that only the L-isoAsp-containing αA66–80 peptide has β-sheet structure and generates amyloid fibrils. Collectively, these observations indicate that isomerization of Aps76 to the Lβ isomer endows β-sheet structure and chaperone function on this peptide.

    更新日期:2020-01-11
  • In-vivo longitudinal changes in thickness of the canine postnatal retina
    Exp. Eye Res. (IF 2.998) Pub Date : 2020-01-10
    Valérie L. Dufour; Yinxi Yu; Wei Pan; Gui-Shuang Ying; Gustavo D. Aguirre; William A. Beltran

    The objectives of the present work were to assess by spectral domain optical coherence tomography (OCT) the changes in thickness of the outer nuclear layer (ONL), the ONL + photoreceptor inner segment (IS), and the retinal thickness, as a function of age in the normal canine retina. OCT retinal scans extending from the edge of the optic nerve head (ONH) along the superior and inferior meridians were captured in both eyes of 17 normal dogs at age ranging from 4 to 119 weeks. The different parameters along the superior and the inferior regions were determined following manual segmentation using the Heidelberg Eye Explorer software. Changes in thickness with age were modeled using one-phase exponential decay models. In vivo OCT imaging results showed no interocular statistically significant differences in ONL, ONL + IS, and retinal thickness at any age. All three parameters were however found to be statistically significantly thicker in the superior vs inferior retina. A rapid thinning of the three layers occurs in both the superior and inferior retina between 4 and 12 weeks of age, before reaching a plateau at around 20 weeks of age. In conclusion, the ONL, ONL + IS, and retinal thickness of the normal canine retina decrease significantly during the first three postnatal months, and is likely attributed to an overall increase in the eye volume and tangential dispersion of the photoreceptor since early photoreceptor developmental cell death is very limited at that age. Establishment of the natural history of ONL, ONL + IS, and retinal thinning will allow a more accurate assessment of the progression of a retinal degenerative condition as well as facilitate the detection of positive rescue effect of novel retinal therapies evaluated in this large animal model.

    更新日期:2020-01-11
  • Gypenosides mediate cholesterol efflux and suppress oxidized LDL induced inflammation in retinal pigment epithelium cells
    Exp. Eye Res. (IF 2.998) Pub Date : 2020-01-10
    Lincoln Biswas; Zhihong Zeng; Annette Graham; Xinhua Shu

    Age-related macular degeneration (AMD) is a predominant cause of visual deficit in aged population. Abnormal accumulation of cholesterol, including oxidized low-density lipoprotein (oxLDL), underneath the retinal pigment epithelium (RPE) cells contributes to the development of AMD. Gypenosides (Gyp) are glycosides extracted from Gynostemma pentaphyllum and have demonstrated protective effects against inflammation and oxidative stress. To determine the therapeutic potential of Gyp for AMD, we investigated its effect on cholesterol trafficking and metabolism and assessed the protective function of Gyp against oxLDL-induced damage in RPE cells. Cholesterol efflux to high-density lipoprotein (HDL) and human serum was significantly increased in RPE cells treated with Gyp when compared to untreated control cells. Expression of cholesterol metabolism (CYP27A1, CYP46A1) and trafficking (TSPO, ABCA1 and ABCG1) genes was also markedly increased in Gyp-treated RPE cells. OxLDL-treated RPE cells had significantly increased cholesterol accumulation and lipid droplet formation. There were marked increases in reactive oxygen species (ROS) generation and proinflammatory cytokines via NF-κB activation in RPE cells treated with oxLDL, while incubation with Gyp rectified these changes. These findings provide pharmacological evidence that Gyp has the potential to treat patients with early onset AMD by promoting cellular cholesterol removal from RPE cells and inhibiting inflammation and oxidative stress.

    更新日期:2020-01-11
  • Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3, Randomized Trial
    Ophthalmology (IF 7.732) Pub Date : 2020-01-10
    Steven Yeh; Rahul N. Khurana; Milan Shah; Christopher R. Henry; Robert C. Wang; Jennifer M. Kissner; Thomas A. Ciulla; Glenn Noronha

    Purpose Injection of pharmacotherapy into the suprachoroidal space, between the sclera and choroid, is an alternative delivery technique developed under the rationale of providing higher drug concentrations to posterior ocular structures compared to other intraocular and periocular injection procedures. This study was conducted to evaluate the safety and efficacy of suprachoroidally injected CLS-TA, a suspension of triamcinolone acetonide, in improving vision among patients with noninfectious uveitis complicated by macular edema (ME). Design The PEACHTREE study was a phase 3 masked, randomized trial. Participants 160 patients with macular edema (ME) secondary to noninfectious uveitis. Patients were required to have a best corrected visual acuity (BCVA) score of ≥5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/800 Snellen equivalent) and ≤70 letters read (20/40) in the study eye. Methods Patients were randomized 3:2 to suprachoroidally injected CLS-TA or sham, with administrations at day 0 and week 12. Main Outcome Measures The primary endpoint was improvement from baseline of ≥15 ETDRS letters in BCVA at week 24. The secondary endpoint was reduction from baseline in central subfield thickness at week 24. Results In the CLS-TA arm, 47% of patients gained ≥15 ETDRS letters in BCVA versus 16% in the control arm (p<0.001), meeting the primary endpoint. Mean reductions in central subfield thickness from baseline were 153 μm versus 18 μm (p<0.001). No serious adverse events (AEs) related to treatment were reported. Corticosteroid-associated AEs of elevated intraocular pressure occurred in 11.5% and 15.6% of CLS-TA and control groups, respectively. Cataract AE rates were comparable (7.3% and 6.3%). Conclusions Patients in the CLS-TA study arm experienced clinically significant improvement in vision relative to the sham procedure, demonstrating the efficacy of suprachoroidal injection of CLS-TA for the treatment of ME in a vision-threatening disorder.

    更新日期:2020-01-11
  • The Association between Medication Adherence and Visual Field Progression in the Collaborative Initial Glaucoma Treatment Study
    Ophthalmology (IF 7.732) Pub Date : 2020-01-10
    Paula Anne Newman-Casey; Leslie M. Niziol; Brenda W. Gillespie; Nancy K. Janz; Paul R. Lichter; David C. Musch

    Purpose To evaluate the relationship between medication adherence and visual field progression in participants randomized to the medication arm of the Collaborative Initial Glaucoma Treatment Study (CIGTS). Design The CIGTS was a randomized, multicenter clinical trial comparing initial treatment with topical medications to trabeculectomy for 607 participants with newly diagnosed glaucoma. Participants Three hundred seven participants randomized to the medication arm of the CIGTS. Methods Participants were followed up at 6-month intervals for up to 10 years. Self-reported medication adherence and visual fields were measured. Medication adherence was assessed by telephone from responses to the question, “Did you happen to miss any dose of your medication yesterday?” The impact of medication adherence on mean deviation (MD) over time was assessed with a linear mixed regression model adjusting for the effects of baseline MD and age, cataract extraction, interactions, and time (through year 8, excluding time after crossover to surgery). Medication adherence was modeled as a cumulative sum of the number of prior visits where a missed dose of medication was reported. Main Outcome Measure Mean deviation over time. Results Three hundred seven subjects (306 with adherence data) were randomized to treatment with topical medications and followed up for an average of 7.3 years (standard deviation, 2.3 years). One hundred forty-two subjects (46%) reported never missing a dose of medication over all available follow-up, 112 patients (37%) reported missing medication at up to one third of visits, 31 patients (10%) reported missing medication at one third to two thirds of visits, and 21 patients (7%) reported missing medication at more than two thirds of visits. Worse medication adherence was associated with loss of MD over time (P = 0.005). For subjects who reported never missing a dose of medication, the average predicted MD loss over 8 years was 0.62 dB, consistent with age-related loss (95% confidence interval [CI], 0.17–1.06; P = 0.007); subjects who reported missing medication doses at one third of visits had a loss of 1.42 dB (95% CI, 0.86–1.98; P < 0.0001); and subjects who reported missing medication doses at two thirds of visits showed a loss of 2.23 dB (95% CI, 1.19–3.26; P < 0.0001). Conclusions This longitudinal assessment demonstrated a statistically and clinically significant association between medication nonadherence and glaucomatous vision loss.

    更新日期:2020-01-11
  • Functional versus functional and anatomical criteria-guided ranibizumab treatment in patients with neovascular age-related macular degeneration – results from the randomized, phase IIIb OCTAVE study
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-09
    Giovanni Staurenghi; Justus G. Garweg; Bianca S. Gerendas; Wayne Macfadden; Boris Gekkiev; Philippe Margaron; Cornelia Dunger-Baldauf; Petr Kolar

    To evaluate the efficacy and safety of two individualized ranibizumab retreatment schemes in neovascular age-related macular degeneration. Patients (N = 671) were randomized (1:1) to receive three initial monthly ranibizumab 0.5 mg injections, then retreatment guided by either best-corrected visual acuity (BCVA) loss (Group I) or BCVA loss and/or signs of disease activity on optical coherence tomography (OCT; Group II). The study was terminated prematurely and the decision to discontinue the study was made by the sponsor. Efficacy analyses were performed on patients who completed 12 months of the originally planned 24-month study. Safety analyses are presented for all safety analyzable patients. Of 671 randomized patients, 305 completed 12 months of the study. For the 12-month completers, baseline mean (standard deviation) BCVA and reading-center evaluated central subfield thickness (CSFT) were comparable [Group I: 60.9 (13.10) letters and 517.7(201.79) μm; Group II: 60.2 (12.21) letters and 515.3 (198.37) μm]. The change from baseline at Month 12 in BCVA was 6.7 (13.48) letters in Group I and 8.3 (13.53) letters in Group II and the change in CSFT was − 161.3 (163.48) μm and − 175.3 (170.45) μm, respectively. The mean number of ranibizumab injections was 8.2 in Group I and 8.4 in Group II. Ranibizumab treatment resulted in visual and anatomic gains at 12 months for both retreatment strategies, with a trend in favor of OCT-guided vs BCVA loss guided retreatment. No new safety signals were seen. www.ClinicalTrials.gov (NCT01780935). Registered 31 January 2013.

    更新日期:2020-01-11
  • A systematic approach to evaluate practice-based process- and outcome data applied to the treatment of neovascular age-related macular degeneration
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-09
    Margriet I. van der Reis; M. Elshout; Tos T. J. M. Berendschot; Yvonne de Jong-Hesse; Carroll A. B. Webers; Jan S. A. G. Schouten

    Following the principles of value-based health care, outcomes and processes of daily-practice eye care need to be systematically evaluated. We illustrate an approach that can be used to support data-driven quality improvements. We used patient data regarding the treatment of neovascular age-related macular degeneration (nAMD). In a cohort study, we reviewed medical records of patients with nAMD confirmed on fluorescein angiography (FA). Patients were treated with intravitreal injections with bevacizumab; ranibizumab; or photodynamic therapy (PDT). Visual acuity (VA), ophthalmic exam results and treatments were recorded. VA was compared between treatments by linear mixed model. Diagnosis was re-evaluated on the original FAs. Outcome analysis was performed by 1) selecting VA as the relevant outcome parameter; 2) Preventing selection by comparing treatments with historical untreated cohort and cohorts from the literature, 3) correcting for confounding due to lesion type, and 4) identifying relevant process variables that affect the outcome. These were severity of disease at presentation, and doctor- and patient dependent process variables. In total, 473 eyes were included. At 12 months, change in VA was 0.54, 0.48, 0.09, and 0.07 LogMAR in the no-treatment, photodynamic therapy (PDT), bevacizumab, and ranibizumab groups, respectively. Lesion type on FA differed between groups. Diagnosis of nAMD could not be confirmed in 104 patients. Patient delay, inaccurate diagnosis and treatment intervals may have impacted outcomes. The effect of PDT was small to absent. Anti-VEGFs were effective and appeared as effective as in RCTs. Correct selection of a comparator cohort and addressing confounding, including confounding by indication and effect modification, are needed to achieve valid results and interpretation. Patient delay, diagnosis accuracy, indication for and application of treatment can potentially be improved to improve treatment outcomes. In a value-based care perspective, systematic evaluation of diagnostic accuracy, treatment indication, protocols, and outcomes of new interventions is needed at an early stage to improve outcomes.

    更新日期:2020-01-11
  • Uveitis–glaucoma–hyphema syndrome with sclera-fixed posterior-chamber two-haptic intraocular lens in a highly myopic eye: a case report
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-10
    Yu Du; Xiangjia Zhu; Jin Yang; Yinglei Zhang; Lei Cai; Yi Lu

    We report a case of uveitis–glaucoma–hyphema (UGH) syndrome in a highly myopic pseudophakic eye with seemingly normal positioning of a two-haptic intraocular lens (IOL). The patient was a 61-year-old woman suffering recurrent episodes of blurred vision, floaters, redness, elevated intraocular pressure (IOP), and pain in the right eye following implantation of a sclera-fixed IOL. The symptoms were alleviated by the systemic and topical administration of IOP-lowering and anti-inflammatory medications. A slit-lamp examination revealed depigmentation and atrophy of the iris, and a quiet anterior chamber in the right eye. Endophthalmitis caused by hypovirulent bacteria and UGH syndrome were both considered. Ultrasound biomicroscopy (UBM) and gonioscopy provided direct evidence of malpositioned IOL haptics, which pushed the root of the iris forward, resulting in persistent mechanical chaffing, the probable cause of UGH syndrome. IOL explantation resolved her symptoms. Negative bacterial culture results for the IOL excluded the possibility of endophthalmitis. Heightened awareness of underlying UGH syndrome and prompt UBM are important when doctors encounter a patient with a sclera-fixed IOL suffering from recurrent anterior segment inflammation and elevated IOP.

    更新日期:2020-01-11
  • Comparison of intraocular pressure measured by ocular response analyzer and Goldmann applanation tonometer after corneal refractive surgery: a systematic review and meta-analysis
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-10
    Hui Zhang; Zhengtao Sun; Lin Li; Ran Sun; Haixia Zhang

    Accurate measurement of intraocular pressure (IOP) after corneal refractive surgery is of great significance to clinic, and comparisons among various IOP measuring instruments are not rare, but there is a lack of unified analysis. Although Goldmann Applanation Tonometer (GAT) is currently the internationally recognized gold standard for IOP measurement, its results are severely affected by central corneal thickness (CCT). Ocular Response Analyzer (ORA) takes certain biomechanical properties of cornea into account and is supposed to be less dependent of CCT. In this study, we conducted the meta-analysis to systematically assess the differences and similarities of IOP values measured by ORA and GAT in patients after corneal refractive surgery from the perspective of evidence-based medicine. The authors searched electronic databases (MEDLINE, EMBASE, Web of science, Cochrane library and Chinese electronic databases of CNKI and Wanfang) from Jan. 2005 to Jan. 2019, studies describing IOP comparisons measured by GAT and ORA after corneal refractive surgery were included. Quality assessment, subgroup analysis, meta-regression analysis and publication bias analysis were applied in succession. Among the 273 literatures initially retrieved, 8 literatures (13 groups of data) with a total of 724 eyes were included in the meta-analysis, and all of which were English literatures. In the pooled analysis, the weighted mean difference (WMD) between IOPcc and IOPGAT was 2.67 mmHg (95% CI: 2.20~3.14 mmHg, p < 0.0001), the WMD between IOPg and IOPGAT was − 0.27 mmHg (95% CI: − 0.70~0.16 mmHg, p = 0.2174). In the subgroup analysis of postoperative IOPcc and IOPGAT, the heterogeneity among the data on surgical procedure was zero, while the heterogeneity of other subgroups was still more than 50%. The comparison of the mean difference of pre- and post-operative IOP (∆IOP) was: mean-∆IOPg > mean-∆IOPGAT > mean-∆IOPcc. IOPcc, which is less dependent on CCT, may be more close to the true IOP after corneal refractive surgery compared with IOPg and IOPGAT, and the recovery of IOPcc after corneal surface refractive surgery may be more stable than that after lamellar refractive surgery.

    更新日期:2020-01-11
  • Comparison of postoperative refractive outcome in eyes undergoing combined phacovitrectomy vs cataract surgery following vitrectomy
    Graefes Arch. Clin. Exp. Ophthalmol. (IF 2.250) Pub Date : 2020-01-10
    Paris G. Tranos, Bruce Allan, Miltiadis Balidis, Athanasios Vakalis, Solon Asteriades, George Anogeianakis, Magda Triantafilla, Nikolaos Kozeis, Panagiotis Stavrakas

    To investigate the accuracy of preoperative biometry in eyes undergoing combined phacovitrectomy and to compare it with eyes having cataract surgery at a later point in time following vitrectomy.

    更新日期:2020-01-11
  • Management of nystagmus in children: a review of the literature and current practice in UK specialist services
    Eye (IF 2.366) Pub Date : 2020-01-09
    J. E. Self; M. J. Dunn; J. T. Erichsen; I. Gottlob; H. J. Griffiths; C. Harris; H. Lee; J. Owen; J. Sanders; F. Shawkat; M. Theodorou; J. P. Whittle
    更新日期:2020-01-10
  • Exploring choroidal angioarchitecture in health and disease using choroidal vascularity index
    Prog. Retin. Eye. Res. (IF 11.768) Pub Date : 2020-01-10
    Rupesh Agrawal; Jianbin Ding; Parveen Sen; Andres Rousselot; Amy Chan; Lisa Nivison-Smith; Xin Wei; Sarakshi Mahajan; Ramasamy Kim; Chitaranjan Mishra; Manisha Agarwal; Min Hee Suh; Saurabh Luthra; Marion R. Munk; Carol Y. Cheung; Vishali Gupta

    The choroid is one of the most vascularized structures of the human body and plays an irreplaceable role in nourishing photoreceptors. As such, choroidal dysfunction is implicated in a multitude of ocular diseases. Studying the choroid can lead to a better understanding of disease pathogenesis, progression and discovery of novel management strategies. However, current research has produced inconsistent findings, partly due to the physical inaccessibility of the choroid and the lack of reliable biomarkers. With the advancements in optical coherence tomography technology, our group has developed a novel quantitative imaging biomarker known as the choroidal vascularity index (CVI), defined as the ratio of vascular area to the total choroidal area. CVI is a potential tool in establishing early diagnoses, monitoring disease progression and prognosticating patients. CVI has been reported in existing literature as a robust marker in numerous retinal and choroidal diseases. In this review, we will discuss the current role of CVI with reference to existing literature, and make postulations about its potential and future applications.

    更新日期:2020-01-10
  • The effects of negative periocular pressure on intraocular pressure
    Exp. Eye Res. (IF 2.998) Pub Date : 2020-01-09
    C. Ross Ethier; Paul Yoo; John P. Berdahl

    Glaucoma is a major cause of blindness, and IOP reduction remains the only clinically-validated therapy. In this study, we analyze a novel IOP-lowering strategy that uses a modest negative pressure (vacuum) applied locally to the periorbital region by a pair of goggles with each lens individually connected to a programmable pump. Motivated by clinical data showing an IOP reduction, we used an existing validated lumped-parameter model of the eye to understand the putative mechanism of this treatment. The model considers aqueous humor dynamics, episcleral venous pressure, and changes in ocular blood volume to describe how IOP changes with time in response to an external perturbation. We find that clinical data are qualitatively and quantitatively consistent with model predictions if we include two primary mechanisms in the model: first, negative pressure application causes a relatively rapid increase in globe volume accompanied by increased blood volume in the eye. Second, negative pressure application reduces episcleral venous pressure, causing a slower adjustment of IOP due to altered aqueous humor dynamics. These results provide testable hypotheses that hopefully will lead to a fuller experimentally-driven understanding of how negative periocular pressure influences IOP. Evaluating the long-term effects of such treatments on glaucoma patients requires further clinical study.

    更新日期:2020-01-09
  • Protective effect inhibiting the expression of miR-181a on the diabetic corneal nerve in a mouse model
    Exp. Eye Res. (IF 2.998) Pub Date : 2020-01-09
    Jianzhang Hu; Yurong Huang; Yi Lin; Jingqiong Lin

    To investigate the protective effect of inhibiting miR-181a on diabetic corneal nerve in mice, we chose male C57BL/6 mice with streptozotocin (STZ) -induced diabetes as animal models. The expression of miR-181a in trigeminal ganglion tissue (TG) of diabetic mice was detected by real-time PCR. In vitro, we cultured mouse trigeminal ganglion neurons and measured the neuronal axon growth when treated under miR-181a antagomir and negative conditions (NTC). Immunofluorescence showed a significant increase in neuronal axon length in trigeminal ganglion cells treated with miR-181a antagomir. In animal models, we performed epithelial scraping and subconjunctival injection of the miR-181a antagomir and miRNA antagomir NTC to observe the corneal nerve repair by corneal nerve staining. miR-181a antagomir subconjunctival injection significantly increased the corneal epithelium healing of diabetic mice compared with that of the NTC group. Meanwhile, corneal nerve staining showed that the repair of corneal nerve endings was significantly promoted. As the targets of the 181a, ATG5 and BCL-2 were previously identified. The results of Western blot showed that the expression of autophagy associated protein ATG5 and LC3B-II and the expression of anti-apoptotic protein Bcl-2 were decreased in the high-glucose cell culture environment and the diabetic TG tissue. The expression of ATG5, LC3B-II and Bcl-2 were significantly increased after miR-181a antagomir treatment compared with negative control group. This study showed that inhibition of miR-181a expression in diabetic mice could increase ATG5-mediated autophagic activation, BCL-2-mediated inhibition of apoptosis, and promote the growth of trigeminal sensory neurons and the regeneration of corneal nerve fibers. It has a protective effect on diabetic corneal neuropathy.

    更新日期:2020-01-09
  • High-throughput transcriptional profiling combined with angiogenesis antibody array analysis in an orbital venous malformation cohort
    Exp. Eye Res. (IF 2.998) Pub Date : 2020-01-08
    Peiwei Chai; Jie Yu; Yongyun Li; Yingyun Shi; Xianqun Fan; Renbing Jia

    Orbital venous malformations (OVMs) are the most common benign orbital vascular disorders in adults and are characterized as enlarging encapsulated vascular neoplasms. These painless lesions grow slowly and become symptomatic with proptosis or visual disturbance. However, the pathogenic mechanism and diagnostic markers of OVMs remain poorly understood. To identify potential pathways involved in OVM formation, a cDNA microarray analysis was conducted with OVM samples and normal vascular tissues. These data were deposited in the National Omics Data Encyclopedia (NODE) database (accession number: OER033009). These pathway expression data were further confirmed by reverse transcription qPCR (RT-qPCR) in an OVM cohort. To explore the diagnostic markers in OVM, an angiogenesis antibody array was analyzed. The altered factors were further validated by enzyme-linked immunosorbent assay (ELISA) in the OVM cohort. Transcriptome screening revealed upregulated autophagy and VEGF pathways and downregulated Hippo, Wnt, hedgehog and vascular smooth muscle contraction signaling pathways in OVM samples. Furthermore, plasma EGF (p < 0.001) and Leptin (p < 0.01) levels were significantly elevated in OVM patients. Here, for the first time, we revealed the transcriptional background and plasma diagnostic markers in OVM, providing a novel understanding of OVM pathogenesis and facilitating the early diagnosis of OVM.

    更新日期:2020-01-09
  • Markedly increased ocular side effect causing severe vision deterioration after chemotherapy using new or investigational epidermal or fibroblast growth factor receptor inhibitors
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-09
    Eunhae Shin; Dong Hui Lim; Jisang Han; Do-Hyun Nam; Keunchil Park; Myung-Ju Ahn; Won Ki Kang; Jeeyun Lee; Jin Seok Ahn; Se-Hoon Lee; Jong-Mu Sun; Hyun Ae Jung; Tae-Young Chung

    We sought to describe corneal epithelial changes after using epidermal (EGFR) or fibroblast growth factor receptor (FGFR) inhibitors as chemotherapy and to clarify incidence and prognosis. Retrospective chart review. Among 6871 patients and 17 EGFR or FGFR inhibitors, 1161 patients (16.9%) referred for ophthalmologic examination. In total, 1145 patients had disease-related or unrelated ocular complications. Among 16 patients with treatment-related ocular complications, three patients had treatment-related radiation retinopathy and one patient showed treatment-related corneal ulcer. Finally the authors identified that, in 12 patients, three EGFR inhibitors and two FGFR inhibitors caused corneal epithelial lesions. Vandetanib, Osimertinib, and ABT-414 caused vortex keratopathy in nine patients, while ASP-5878 and FPA-144 caused epithelial changes resembling corneal dysmaturation in three patients. The mean interval until symptoms appeared was 246 days with vandetanib, 196 days with osimertinib, 30 days with ABT-414, 55 days with ASP-5878, and 70 days with FPA-144. The mean of the lowest logarithm of minimal angle of resolution visual acuity results of the right and left eyes after chemotherapy were 0.338 and 0.413. The incidence rates of epithelial changes were 15.79% with vandetanib, 0.5% with osimertinib, 100% with ABT-414, 50.0% with ASP-5878, and 18.2% with FPA-144. After excluding deceased patients and those who were lost to follow-up or still undergoing treatment, we confirmed the reversibility of corneal lesions after the discontinuation of each agent. Seven patients showed full recovery of their vision and corneal epithelium, while three achieved a partial level of recovery. Although patients diagnosed with glioblastoma used prophylactic topical steroids before and during ABT-414 therapy, all developed vortex keratopathy. EGFR and FGFR inhibitors are chemotherapy agents that could make corneal epithelial changes. Contrary to the low probability of ocular complication with old EGFR drugs, recently introduced EGFR and FGFR agents showed a high incidence of ocular complication with severe vision distortion. Doctors should forewarn patients planning chemotherapy with these agents that decreased visual acuity could develop due to corneal epithelial changes and also reassure them that the condition could be improved after the end of treatment without the use of steroid eye drops. This study was approved by the institutional review board (IRB) of Samsung Medical Center (IRB no. 2019–04-027) and was conducted according to the principles expressed in the Declaration of Helsinki.

    更新日期:2020-01-09
  • Case report: what gives the myopic tilted disc an oval appearance?
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-09
    Kyoung Min Lee; Martha Kim; Seok Hwan Kim

    Myopic tilted disc, observed as an oval disc, has been alleged to be a funduscopic en-face manifestation of excessive optic nerve head (ONH) sloping or tilting. Here, we report the case of a myopic child showing a developing oval disc in fundus photos during axial elongation, but without progressive tilting in spectral-domain optical coherence tomography (SD-OCT) images. By merging B-scan SD-OCT images of the ONH and macula, the curvature of the posterior pole, including both the fovea and ONH, was reconstructed and compared before and after 2 years of axial elongation. Despite the marked increase of disc ovality, the posterior polar curvature was rarely changed. The preponderance of optic disc change was induced by the shift of the temporal disc margin in the nasal direction. This shifting alone imitated an increase of tilt angle but one that was still far smaller than the required degree of tilt for ONH-tilt-based disc ovality. To clarify, we calculated the required extent of axial elongation to obtain a substantial degree of ONH tilt when considering the adjacency of the fovea and the ONH. Without a focal increase of posterior polar curvature, which is to say posterior staphyloma, such change is not possible until the axial length increases extraordinarily. The most prominent change in the development of myopic tilted disc, which change gives it an oval appearance and imitates a tilt when measured, is actually not a tilt but rather a shift of the temporal disc margin.

    更新日期:2020-01-09
  • Ophthalmological findings in children with autism spectrum disorder
    Graefes Arch. Clin. Exp. Ophthalmol. (IF 2.250) Pub Date : 2020-01-09
    Raoul Kanav Khanna, Klara Kovarski, Sophie Arsene, Marine Siwiaszczyk, Pierre-Jean Pisella, Frédérique Bonnet-Brilhault, Magali Batty, Joëlle Malvy

    Eye pathology could be related to atypical visual behaviours and impaired social communication through visual cues in children with autism spectrum disorder (ASD). The main purpose of this prospective study was to assess ophthalmological disorders in children with ASD and to investigate the relationships with intellectual disability (ID) and ASD severity.

    更新日期:2020-01-09
  • Nuclear factor-kappa beta signaling is required for transforming growth factor Beta-2 induced ocular hypertension
    Exp. Eye Res. (IF 2.998) Pub Date : 2020-01-08
    Humberto Hernandez; Amanda L. Roberts; Colleen M. McDowell

    A major risk for the development of primary open-angle glaucoma (POAG) is elevated intraocular pressure (IOP). Elevated IOP is caused by increased outflow resistance due in part to excessive extracellular matrix (ECM) deposition in the trabecular meshwork (TM). The role of transforming growth factor beta 2 (TGFβ2) in inducing ECM production is well understood. Recent studies suggest that toll-like receptor 4 (TLR4) plays an important role in fibrogenesis. We have previously described a crosstalk between TGFβ2 and TLR4 in the development of ocular hypertension and glaucomatous TM damage. Nuclear factor-kappa beta (NF-κB) is critical for TLR4 signaling. To determine the transactivation of NF-κB, TM cells were stimulated with cellular fibronectin containing the EDA isoform (cFN-EDA), TGFβ2, or lipopolysaccharide (LPS) in combination with a selective TLR4 inhibitor. cFN-EDA, TGFβ2, and LPS all induced transactivation of NF-κB and inhibition of TLR4 blocked the effect of each treatment paradigm. To evaluate the role of NF-κB in IOP regulation, we utilized our inducible mouse model of ocular hypertension by injection of Ad5.TGFβ2 in mice harboring a mutation in NF-κB and wild-type controls. IOP was measured over time and eyes accessed by immunohistochemistry for the ECM protein FN and the specific FN-EDA isoform. Ad5.TGFβ2 induced ocular hypertension and expression of FN and FN-EDA in wild-type mice, but mutation in NF-κB blocked the effect. These data suggest that NF-κB is necessary for TGFβ2-induced ECM production and ocular hypertension and the transactivation of NF-κB is dependent on both TGFβ2 and TLR4.

    更新日期:2020-01-08
  • Nox4-mediated ROS production is involved, but not essential for TGFβ-induced lens EMT leading to cataract
    Exp. Eye Res. (IF 2.998) Pub Date : 2020-01-08
    S.J. Das; T. Wishart; K. Jandeleit-Dahm; F.J. Lovicu

    The reactive oxygen species (ROS) producing enzyme, NADPH oxidase 4 (Nox4),is upregulated in response to TGFβ in lens epithelial cells in vitro, and its selective inhibition was shown to block aspects of TGFβ-induced epithelial-mesenchymal transition (EMT). In the present in situ study we validate the role(s) of Nox4 in TGFβ-induced lens EMT leading to anterior subcapsular cataract (ASC) formation. Mice overexpressing TGFβ in the lens, that develop ASC, were crossed to Nox4-deficient mice. When comparing mice overexpressing TGFβ in lens, to mice that were also deficient for Nox4, we see the delayed onset of cataract, along with a delay in EMT protein markers normally associated with TGFβ-induced fibrotic cataracts. In the absence of Nox4, we also see elevated levels of ERK1/2 activity that was shown to be required for TGFβ/Smad2/3-signaling. qRT-PCR revealed upregulation of Nox2 and its regulatory subunit in TGFβ-overexpressing lens epithelial cells devoid of Nox4. Taken together, these findings provide an improved platform to delineate putative Nox4 (and ROS) interactions with Smad2/3 and/or ERK1/2, in particular in the development of fibrotic diseases, such as specific forms of cataract.

    更新日期:2020-01-08
  • Quantitative analysis of metabolites in glucose metabolism in the aqueous humor of patients with central retinal vein occlusion
    Exp. Eye Res. (IF 2.998) Pub Date : 2020-01-08
    Pinghui Wei; Meiqin He; He Teng; Guoge Han

    Quantitative analysis of aqueous humor (AH) was performed to investigate glucose metabolism in patients with central retinal vein occlusion (CRVO), and to explore metabolic changes after anti-vascular endothelial growth factor (VEGF) treatment. AH samples were collected from 35 patients. Participants diagnosed with CRVO (n = 15) were compared to participants who underwent cataract surgery (n = 20). Thirteen of the participants with CRVO received second-round anti-VEGF treatments. Ultra-high performance liquid chromatography tandem-mass spectrometry (UHPLC-MS/MS) was used to quantify metabolites of the AH. Central macular thickness (CMT) and retinal ganglion cell layer (RGC) thickness were measured using spectral-domain optical coherence tomography. Thirteen metabolites involved in glucose metabolism were identified. Among these metabolites, succinate, glutamate, and glutamine were significantly decreased for the CRVO group (p = 0.028, 0.009, and 0.017, respectively). The α-ketoglutarate/citrate (K/C) ratio had a significant positive correlation with glutamine levels for both control (r = 0.922, p < 0.001) and CRVO groups (r = 0.674, p = 0.006). A significant increase in lactate was observed after intravitreal anti-VEGF administration (t = 2.273, p = 0.045); the change in CMT was negatively correlated with this increase (r = −0.745, p = 0.003). The alteration of RGC thickness was negatively correlated with increases in both glutamine (r = −0.619, p = 0.024) and glucose (r = −0.754, p = 0.003). These results indicate that, compared to glucose metabolism, glutamine was significantly decreased in the AH of patients with CRVO, and may therefore serve as a potential target for CRVO therapy. The glycolytic pathway might be enhanced after intravitreal anti-VEGF injection, which is an important insight into CRVO pathophysiology.

    更新日期:2020-01-08
  • Comparative efficacy evaluation of inverted internal limiting membrane flap technique and internal limiting membrane peeling in large macular holes: a systematic review and meta-analysis
    BMC Ophthalmol. (IF 1.431) Pub Date : 2020-01-08
    Yu Shen; Xiaoqin Lin; Luyi Zhang; Miaoqin Wu

    The purpose of this study was to compare the anatomical and visual outcomes of inverted internal limiting membrane (ILM) flap technique and internal limiting membrane peeling in large macular holes (MH). Related studies were reviewed by searching electronic databases of Pubmed, Embase, Cochrane Library. We searched for articles that compared inverted ILM flap technique with ILM peeling for large MH (> 400 μm). Double-arm meta-analysis was performed for the primary end point that was the rate of MH closure, and the secondary end point was postoperative visual acuity (VA). Heterogeneity, publication bias, sensitivity analysis and subgroup analysis were conducted to guarantee the statistical power. This review included eight studies involving 593 eyes, 4 randomized control trials and 4 retrospective studies. After sensitivity analysis for eliminating the heterogeneity of primary outcome, the pooled data showed the rate of MH closure with inverted ILM flap technique group was statistically significantly higher than ILM peeling group (odds ratio (OR) = 3.95, 95% confidence interval (CI) = 1.89 to 8.27; P = 0.0003). At the follow-up duration of 3 months, postoperative VA was significantly better in the group of inverted ILM flap than ILM peeling (mean difference (MD) = − 0.16, 95% CI = − 0.23 to 0.09; P < 0.00001). However, there was no difference in visual outcomes between the two groups of different surgical treatments at relatively long-term follow-up over 6 months (MD = 0.01, 95% CI = − 0.12 to 0.15; P = 0.86). Vitrectomy with inverted ILM flap technique had a better anatomical outcome than ILM peeling. Flap technique also had a signifcant visual gain in the short term, but the limitations in visual recovery at a longer follow-up was found.

    更新日期:2020-01-08
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