To determine the expressions of SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) genes in human and mouse ocular cells and comparison to ...other tissue cells.
Human conjunctiva and primary pterygium tissues were collected from pterygium patients who underwent surgery. The expression of ACE2 and TMPRSS2 genes was determined in human primary conjunctival and pterygium cells, human ocular and other tissue cell lines, mesenchymal stem cells as well as mouse ocular and other tissues by reverse transcription-polymerase chain reaction (RT-PCR) and SYBR green PCR.
RT-PCR analysis showed consistent expression by 2 ACE2 gene primers in 2 out of 3 human conjunctival cells and pterygium cell lines. Expression by 2 TMPRSS2 gene primers could only be found in 1 out of 3 pterygium cell lines, but not in any conjunctival cells. Compared with the lung A549 cells, similar expression was noted in conjunctival and pterygium cells. In addition, mouse cornea had comparable expression of Tmprss2 gene and lower but prominent Ace2 gene expression compared with the lung tissue.
Considering the necessity of both ACE2 and TMPRSS2 for SARS-CoV-2 infection, our results suggest that conjunctiva would be less likely to be infected by SARS-CoV-2, whereas pterygium possesses some possibility of SARS-CoV-2 infection. With high and consistent expression of Ace2 and Tmprss2 in cornea, cornea rather than conjunctiva has higher potential to be infected by SARS-CoV-2. Precaution is necessary to prevent possible SARS-CoV-2 infection through ocular surface in clinical practice.
Pterygia are common conjunctival degenerations with well-documented risk factors but an unclear pathogenesis. Better understanding of the pathogenesis of pterygium could lead to improved surgical ...outcomes and decreased postoperative recurrence. Currently, pterygium excision with conjunctival autograft remains the preferred surgical technique to decrease pterygium recurrence. Many adjuvant therapies have been used in pterygium surgery to varying degrees of success. Topical cyclosporine, an immunosuppressive medication, in conjunction with conjunctival autograft was found to be most successful in decreasing pterygium recurrence according to a recent meta-analysis. Other adjuvant therapies such as mitomycin-C (MMC), 5-fluorouracil (5-FU), and beta-irradiation have also been used, though usage of these may cause multiple adverse effects. Recent research indicates that interactions between mouse double minute 2 (MDM2) and p53 could play a role in the occurrence of pterygium. Nutlin, an MDM2 antagonist, was found to have significantly less toxicity in conjunctival cells when compared with MMC on laboratory analysis of pterygium samples.
The precorneal tear film is maintained by blinking and exhibits different phases in the tear cycle. The tear film serves as the most anterior surface of the eye and plays an important role as a first ...refractive component of the eye. Alterations in tear film dynamics may cause both vision-related and ocular surface-related symptoms. Although the optical quality associated with the tear film dynamics previously received little attention, objective measurements of optical quality using wavefront sensors have enabled us to quantify optical aberrations induced by the tear film. This has provided an objective method for assessing reduced optical quality in dry eye; thus, visual disturbances were included in the definition of dry eye disease in the 2007 Dry Eye Workshop report. In addition, sequential measurements of wavefront aberrations have provided us with valuable insights into the dynamic optical changes associated with tear film dynamics. This review will focus on the current knowledge of the mechanisms of wavefront variations that are caused by different aspects of tear film dynamics: specifically, quality, quantity and properties of the tear film, demonstrating the respective effects of dry eye, epiphora and instillation of eye drops on the quality of vision.
To compare the corneal deformation response, central corneal thickness (CCT), and intraocular pressure (IOP) measurements and their test-retest variability obtained with an ultrahigh-speed ...Scheimpflug camera between normal and keratoconus eyes.
Three consecutive measurements were obtained using Corvis ST. The following parameters were analyzed: A1 and A2 length (length of flattened cornea at first and second applanation), A1 and A2 velocity (deformation velocity until first and second applanation), corneal deformation amplitude (deformation amplitude of cornea at the highest concavity), peak distance (distance of two apices of cornea at time of highest concavity), and radius of corneal curvature at the time of maximum deformation. Repeatability coefficient and intraclass correlation coefficient were measured. Linear mix models were used to adjust for the effect of age, CCT, and IOP on corneal deformation response parameters.
Twelve normal subjects and 12 keratoconus patients were included. Data from only one eye of each participant were randomly selected for analysis. Significant differences were found in corneal deformation amplitude (p < 0.001) and radius of corneal curvature (p < 0.001) between normal and keratoconus eyes after adjusting for age, CCT, and IOP. Although there was no significant difference of intraclass correlation coefficient between the groups, repeatability coefficient values of A1 and A2 length, A1 velocity, and peak distance were significantly smaller in normal eyes as compared with keratoconus eyes (p ≤ 0.023).
Corvis ST showed adequate repeatability for measurement of corneal deformation amplitude, CCT, and IOP in normal and keratoconus eyes. It may be used to understand ocular pathologies associated with altered biomechanical properties.
•Fourier analysis of the corneal power is useful to evaluate corneal irregular astigmatism.•With optical coherence tomography, different stages of keratoconus can be evaluated.•Posterior irregular ...astigmatism shows the highest ability to identify earliest keratoconus.
To investigate the diagnostic capability of Fourier indices in detecting clinical or subclinical keratoconus (KC).
Prospective cross-sectional study.
The study included 126 eyes with clinical KC (50 KC without any corneal scar, 50 KC with anterior corneal scar, and 26 KC with posterior scar having a history of acute corneal hydrops), 50 with topographic KC (without clinical signs), 50 with pre-topographic KC (normal topography without clinical signs), and 50 controls.
Corneal tomographic data were obtained using anterior segment optical coherence tomography (OCT). Fourier analysis decomposed dioptric data from both anterior and posterior corneal surface into spherical, regular astigmatism, asymmetry, and higher-order irregularity components. The discriminating ability of the Fourier indices of pre-topographic KC, topographic KC, and clinical KC from controls were assessed after quantitative Fourier analysis of irregular corneal astigmatism.
Posterior asymmetry and higher-order irregularity components were significantly greater in pre-topographic KC eyes than those in controls (P < .001 for both), with the highest area under the receiver operating characteristic curve (AUROC) of 0.778 and 0.709, respectively. The same was true for anterior asymmetry, posterior asymmetry, and posterior higher-order irregularity components in topographic KC (AUROC of 0.945, 0.941, and 0.893, respectively), whereas it was >0.948 for all Fourier components in clinical KC.
Fourier analysis using OCT can evaluate anterior and posterior corneal irregular astigmatism of various KC stages, from very mild to advanced, including severe cases with corneal scar. Irregular astigmatism indices from the posterior corneal surface showed the highest AUROC values in discriminating early KC stages.
Dry eye disease is a common ocular condition affecting millions of people worldwide. Artificial tears are the first line therapy for the management of dry eye disease. Artificial tear formulations ...contain a variety of active ingredients, biologically active excipients, and preservatives. Many of these formulations are also available as preservative-free. This study was conducted to inspect artificial tear formulations currently marketed in the United States for their active ingredients, biologically relevant excipients, and preservatives. The marketed artificial tears were examined at various US retail pharmacy chains and using the manufacturers' website to compile information about active ingredients, inactive ingredients, and preservatives. The currently marketed artificial tears can be grouped into four categories based on their active ingredients. The artificial tears also contain biologically active chemicals listed as inactive ingredients, which have osmoprotectant, humectant, and tear film lipid layer or mucous layer mimicking properties. Most artificial tears contain vanishing type preservatives such as purite or sodium perborate and safer quaternary compound polyquaternium-1. The majority of these artificial tear formulations are also available as preservative-free single dose unit. The study provides a formulary of artificial tears based on active ingredients, biologically active excipients, and the preservative-free option. The formulary should assist healthcare providers in making a stepwise and rational selection of appropriate artificial tears for patients suffering from dry eye disease.
According to the World Health Organization World Report on Vision 2019, there are at least 2.2 billion visually impaired people worldwide, with at least 1 billion possessing a vision impairment that ...should have been prevented or that is yet to be tackled (World Health Organization, 2019). In the AI-based medical image processing field, it is expensive and time-consuming to obtain the labels of medical data. ...it is advisable to utilize unlabeled data to improve the performance of the algorithms. With the development of imaging engineering techniques and the collaboration between clinicians and engineering scientists, we would be able to develop more automatic and precise techniques, which can help clinicians to diagnose and manage patients with visual system disorders, and benefit the patients.
Corneal imaging is essential for diagnosing and management of a wide variety of ocular diseases. Corneal topography is used to characterize the shape of the cornea, specifically, the anterior surface ...of the cornea. Most corneal topographical systems are based on Placido disc that analyse rings that are reflected off the corneal surface. The posterior corneal surface cannot be characterized using Placido disc technology. Imaging of the posterior corneal surface is useful for diagnosis of corneal ectasia. Unlike corneal topographers, tomographers generate a three‐dimensional recreation of the anterior segment and provide information about the corneal thickness. Scheimpflug imaging is one of the most commonly used techniques for corneal tomography. The cross‐sectional images generated by a rotating Scheimpflug camera are used to locate the anterior and posterior corneal surfaces. The clinical uses of corneal topography include, diagnosis of corneal ectasia, assessment of corneal astigmatism, and refractive surgery planning. This review will discuss the applications of corneal topography and tomography in clinical practice.
Previously, we demonstrated that Krüppel-like factor 4 (KLF4) promotes corneal epithelial (CE) homeostasis by suppressing epithelial-mesenchymal transition (EMT) and TGF-β signaling. As TGF-β affects ...epithelial apicobasal polarity (ABP) and plane of division, we investigated the role of KLF4 in these processes.
Klf4 was ablated in adult ternary transgenic Klf4Δ/ΔCE (Klf4LoxP/LoxP/Krt12rtTA/rtTA/Tet-O-Cre) mouse CE using doxycycline chow. ABP and plane of division markers' expression in Klf4Δ/ΔCE and human ocular surface squamous neoplasia (OSSN) tissues relative to controls was evaluated by quantitative PCR, immunoblots, and/or immunofluorescent staining.
Klf4Δ/ΔCE CE cells displayed downregulation of apical Pals1 and Crumbs1, apicolateral Par3, and basolateral Scribble, as well as upregulation of Rho family GTPase Cdc42, suggesting disruption of ABP. Phalloidin staining revealed that the Klf4Δ/ΔCE CE actin cytoskeleton is disrupted. Klf4Δ/ΔCE cells favored vertical plane of division within 67.5° to 90° of the CE basement membrane (39% and 47% of the dividing cells relative to 23% and 26% in the control based on phospho-histone-H3 and survivin, respectively), resulting in more dividing cells within the Klf4Δ/ΔCE CE as reported previously. KLF4 was downregulated in human OSSN tissues that displayed EMT and downregulation of PAR3, PALS1, and SCRIB, consistent with a protective role for KLF4.
By demonstrating that Klf4 ablation affects CE expression of ABP markers and Cdc42, cytoskeletal actin organization, and the plane of cell division and that KLF4 is downregulated in OSSN tissues that display EMT and lack ABP, these results elucidate the key integrative role of KLF4 in coordinating CE cell polarity and plane of division, loss of which results in OSSN.
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