scholarly journals Critical Analysis of Corneal Cross-Linking (Part-II): Resolving the Controversial Issues (Theory Versus Measurements)

2021 ◽  
Author(s):  
Jui-Teng Lin
Keyword(s):  
Light Intensity ◽  
Scaling Laws ◽  
Uv Light ◽  
Corneal Thickness ◽  
Cross Linking ◽  
Type I ◽  
Controversial Issues ◽  
Type Ii ◽  
Stromal Tissue ◽  
Theory Versus

To resolve the controversial issues of UV-light-initiatedcornealcollagen cross-linking (CXL) by theoretical formulas and measured clinical outcomes. The controversial issues are addressed and resolved by analytical formulas including: the validation of Bunsen Roscoe law (BRL), the cutoff light intensity, the minimum corneal thickness, the demarcation line depth, the role of oxygen riboflavin (RF) concentration. The overall CXL efficacy is governed by UV-A light intensity, dose, exposure time, mode of exposure (pulsed or CW), riboflavin concentration, diffusion and drops pre-operation and interoperation administration, concentration of oxygen in the stromal tissue (pre-op and inter-op), and environmental conditions. The length of the riboflavin presoaking time and viscosity of the riboflavin film also affect the crosslink depth. Analytic formulas are derived for the scaling laws for type-I and type-II efficacy, given by the square-root of light intensity, and light dose, respectively. The controversial issues of CXL may be partially resolved via analytic formulas, and compared with measurements. The scaling laws of type-I and type-II efficacy are different and given by analytic formulas. Our formulas also predict the maximum light intensity and the minimum corneal thickness, which are consistent with measurements.

scholarly journals Critical Analysis of Corneal Cross-linking (Part-II): Resolving the Controversial Issues (Theory versus Measurements)

2021 ◽  
pp. 23-34
Author(s):  
Jui-Teng Lin
Keyword(s):  
Light Intensity ◽  
Scaling Laws ◽  
Uv Light ◽  
Corneal Thickness ◽  
Cross Linking ◽  
Type I ◽  
Controversial Issues ◽  
Type Ii ◽  
Stromal Tissue ◽  
New Vision

Aims: To resolve the controversial issues of UV-light-initiated corneal collagen cross-linking (CXL) by theoretical formulas and measured clinical outcomes. Study Design:  Analysis and measured data of CXL. Place and Duration of Study: New Vision Inc, Taipei, between June 2021 and August 2021. Methodology: The controversial issues are addressed and resolved by analytical formulas including: the validation of Bunsen Roscoe law (BRL), the cutoff light intensity, the minimum corneal thickness, the demarcation line depth, the role of oxygen and riboflavin concentration. The overall CXL efficacy is governed by UV-A light intensity, dose, exposure time, mode of exposure (pulsed or CW), the riboflavin concentration, diffusion and drops pre-operation and interoperation administration, the concentration of oxygen in the stromal tissue (pre-op and inter-op), and environmental conditions. The length of the riboflavin presoaking time and viscosity of the riboflavin film also affect the crosslink depth. Analytic formulas are derived for the scaling laws for type-I and type-II efficacy, given by the square root of light intensity, and light dose, respectively. Conclusion: The controversial issues of CXL may be partially resolved via analytic formulas, and compared with measurements. The scaling laws of type-I and type-II efficacy are different and given by analytic formulas. Our formulas also predict the maximum light intensity and the minimum corneal thickness, which are consistent with measurements.

scholarly journals Critical Analysis of Corneal Cross-linking (Part-I): Formulas for Efficacy, Safety Dose, Minimum Thickness, Demarcation Line Depth and the Role of Oxygen

2021 ◽  
pp. 29-41
Author(s):  
Sheng-Fu Cheng ◽  
Jui-Teng Lin
Keyword(s):  
Steady State ◽  
Light Intensity ◽  
Corneal Thickness ◽  
Transient State ◽  
Threshold Dose ◽  
Type I ◽  
Type Ii ◽  
Minimum Thickness ◽  
Demarcation Line ◽  
Line Depth

Purpose: To update and derive formulas for the efficacy and kinetics of corneal collagen crosslinking (CXL) including both type-I and oxygen-mediated type-II mechanisms, the role of oxygen, the initiator regeneration, safety dose, minimum corneal thickness and demarcation line depth. Study Design: Modeling the kinetics of CXL in UV light and using riboflavin as the photosensitizer. Place and Duration of Study: Taipei, Taiwan, between June, 2021 and July, 2021. Methodology: Coupled kinetic equations are derived under the quasi-steady state condition for the 2-pathway mechanisms of CXL. For type-I CXL, the riboflavin (RF) triplet state [T] may interact directly with the stroma collagen substrate [A] to form radical (R) and regenerate initiator. For type-II process, [T] interacts with oxygen to form a singlet oxygen [1O2]. Both reactive radical (R) and [1O2], can interact with the substrate [A]) for crosslinking. Based on a safety dose and a threshold dose, formulas for the minimum corneal thickness and demarcation line depth (DLD) are derived. Results: Our updated theory/modeling showed that oxygen plays a limited and transient role in the process, in consistent with that of Kamave. In contrary, Kling et al believed that type-II is the predominant mechanism, which however conflicting with the epi-on CXL results. For both type-I and type-II, a transient state conversion (crosslink) efficacy in an increasing function of light intensity (or dose), whereas, its steady state efficacy is a deceasing function of light intensity. RF depletion in type-I is compensated by the RF regeneration term (RGE) which is a decreasing function of oxygen. For the case of perfect regeneration case (or when oxygen=0), RF is a constant due to the catalytic cycle. Unlike the conventional Dresden rule of 400 um thickness, thin cornea CXL is still safe as far as the dose is under a threshold dose (E*), based on our minimum thickness formula (Z*). Our formula for thin cornea is also clinically shown by Hafez et al for ultra thin (214 nm) CXL. Conclusion: For both type-I and type-II, the transient state conversion (crosslink) efficacy in an increasing function of light intensity (or dose), whereas, its steady state efficacy is a deceasing function of light intensity. CXL for ultra thin corneas are still safe, as far as it is under a threshold dose (E*), based on our minimum thickness (Z*) formula, which has a similar tend as that of demarcation line depth (Z').

scholarly journals Physiological and Clinical Significance of Disordered Cross-Linking of Fibrin

1977 ◽  
Author(s):  
L. Lorand
Keyword(s):  
Class Ii ◽  
Class I ◽  
Cross Linking ◽  
Type I ◽  
Type Ii ◽  
Zymogen Activation ◽  
Primary Defect ◽  
Plasma Clot ◽  
Autoimmune Antibodies ◽  
Hereditary Disorders

Disorders of fibrin stabilization are hemorrhagic conditions in which the patient’s plasma clot is lacking in inter-fibrin γ-glutamyl-ε-lysine isopeptide linkages. The primary defect occurs either because no fibrinoligase (FXIIIa) activity can be generated or because the enzyme cannot act on fibrin in the patient’s plasma. Distinction is made between hereditary disorders (Class I) and those appearing later in life because of an acquired inhibitor (Class II) directed against one of the steps on the pathway of fibrin stabilization: Of the genetic deficiencies (Class I), Type I is characterized by a lack of zymogen activity in plasma and Type II by the unreactivity of the cross-linking sites of the patient’s fibrin [“dysfibrin(ogen)emias”] towards fibrinoligase.There are three varieties of Class II abnormalities. In Type I, the acquired inhibitor interferes with zymogen activation. Type II inhibitors affect transamidation by competing against fibrin for the enzyme. The Type III inhibitor combines with fibrin rendering it unreactive towards fibrinoligase. The Type I and III inhibitors appear to be autoimmune antibodies.(Ann. N. Y. Acad. Sei., 202, 6, 1972).Differential diagnostic criteria for this family of molecular disorders will be discussed.

scholarly journals Modeling the Dynamic Concentration Profiles and Efficacy of Type-I and Type-II Photopolymerization

2018 ◽  
Author(s):  
Jui-Teng Lin ◽  
Da-Chuan Cheng ◽  
Kuo-Ti Chen ◽  
Hsia-Wei Liu
Keyword(s):  
Steady State ◽  
Light Intensity ◽  
Light Exposure ◽  
Light Dose ◽  
Type I ◽  
Concentration Profiles ◽  
Type Ii ◽  
Photoinitiated Polymerization ◽  
Lower Light ◽  
Dynamic Concentration

The kinetics and efficacy profiles of photoinitiated polymerization are theoretically presented. For the same dose, lower light intensity achieves a higher steady-state-efficacy (SSE) in type-I; in contrast, type-II has an equal SSE. Higher light intensity has a faster rising efficacy, due to faster depletion of photoinitiator (PS) concentration. However, type-II process is also affected by the available oxygen. Higher light intensity produces more efficient singlet oxygen, resulting a higher transient efficacy, in which all intensities reach the same SSE when oxygen is completely depleted. With external oxygen, type-II efficacy increases with time, otherwise, it is governed only by the light dose, i.e., same dose achieves same efficacy. Moreover, type-II has an efficacy follows Bunsen Roscoe law (BRL), whereas type-I follows non-BRL. The measured type-I efficacy and gelation profile are analyzed by our analytic formulas. Schematics of the photocrosslinking stage defined by the availability of oxygen is developed, where both type-I and –II coexist until the oxygen is depleted. The overall efficacy may be enhanced by resupply of PS or oxygen during the light exposure. The roles of light dose and PS concentration on the efficacy of photoinitiated polymerization should be are governed a new concept of a volume efficacy (Ve), defined by the product of the crosslink (or gelation) depth (CD) and local [efficacy].

scholarly journals Clinical and Ultrasound Biomicroscopic Characteristics of Congenital Fibrovascular Pupillary Membrane-Induced Secondary Glaucoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Yingting Zhu ◽  
Lei Fang ◽  
Yimin Zhong ◽  
Julius Oatts ◽  
Ying Han ◽  
...  
Keyword(s):  
Anterior Chamber ◽  
Optic Neuropathy ◽  
Axial Length ◽  
Corneal Thickness ◽  
Anterior Chamber Depth ◽  
Case Series ◽  
Secondary Glaucoma ◽  
Glaucomatous Optic Neuropathy ◽  
Type I ◽  
Type Ii

Purpose: The purpose of this study was to describe and summarize the clinical features of congenital fibrovascular pupillary membrane-induced secondary glaucoma (CFPMSG).Design: Cross-sectional case series.Methods: Eyes of 32 patients with CFPMSG were enrolled. Demographic data, including gender, laterality, age at presentation, and age at onset of glaucoma were collected. Patients underwent comprehensive ophthalmic examinations and ultrasound biomicroscopy (UBM). CFPMSG eyes were classified into three groups based on UBM findings and intergroup analysis was performed using ANOVA.Results: The average age at presentation was 2.4 ± 4.6 months (mean ± SD) and at glaucoma onset was 3.8 ± 4.5 months. Compared to normal fellow eyes, all affected eyes had increased intraocular pressure (IOP), axial length, corneal diameter, and central corneal thickness, and decreased anterior chamber depth (ACD) (all P ≤ 0.001). Twenty-two affected eyes (68.8%) had evidence of glaucomatous optic neuropathy. Based on iris configuration on UBM, eyes were classified as 53% type I (“U” shape), 34% type II (“Y” shape), and 13% type III (no anterior chamber). IOP in types II (33.8 ± 5.9 mmHg) and III (35.2 ± 5.9 mmHg) was significantly higher than in type I eyes (26.5 ± 5.1 mmHg). The ACD was shallower in type II compared to type I (P = 0.045).Conclusion: Congenital fibrovascular pupillary membrane-induced secondary glaucoma is characterized by ocular hypertension, corneal enlargement and edema, axial length elongation, and glaucomatous optic neuropathy. Glaucoma in this condition is secondary to pupillary block and angle-closure. UBM provides important information for the diagnosis and classification of CFPMSG. This novel classification system demonstrated varying levels of severity and may guide on management of this disease.

scholarly journals Sec61p is adjacent to nascent type I and type II signal-anchor proteins during their membrane insertion.

1993 ◽  
Vol 121 (4) ◽  
pp. 743-750 ◽  
Author(s):  
S High ◽  
S S Andersen ◽  
D Görlich ◽  
E Hartmann ◽  
S Prehn ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Cross Linking ◽  
Secretory Proteins ◽  
Membrane Insertion ◽  
Type I ◽  
Type Ii ◽  
Core Component ◽  
Signal Anchor ◽  
Membrane Components ◽  
Anchor Proteins

We have identified membrane components which are adjacent to type I and type II signal-anchor proteins during their insertion into the membrane of the ER. Using two different cross-linking approaches a 37-38-kD nonglycosylated protein, previously identified as P37 (High, S., D. Görlich, M. Wiedmann, T. A. Rapoport, and B. Dobberstein. 1991. J. Cell Biol. 113:35-44), was found adjacent to all the membrane inserted nascent chains used in this study. On the basis of immunoprecipitation, this ER protein was shown to be identical to the recently identified mammalian Sec61 protein. Thus, Sec61p is the principal cross-linking partner of both type I and type II signal-anchor proteins during their membrane insertion (this work), and of secretory proteins during their translocation (Görlich, D., S. Prehn, E. Hartmann, K.-U. Kalies, and T. A. Rapoport. 1992. Cell. 71:489-503). We propose that membrane proteins of both orientations, and secretory proteins employ the same ER translocation sites, and that Sec61p is a core component of these sites.

scholarly journals Type II Keratins Are Phosphorylated on a Unique Motif during Stress and Mitosis in Tissues and Cultured Cells

2002 ◽  
Vol 13 (6) ◽  
pp. 1857-1870 ◽  
Author(s):  
Diana M. Toivola ◽  
Qin Zhou ◽  
Luc S. English ◽  
M. Bishr Omary
Keyword(s):  
Cultured Cells ◽  
Uv Light ◽  
Ex Vivo ◽  
Psoriatic Skin ◽  
Type I ◽  
Type Ii ◽  
Intermediate Filament Proteins ◽  
Phosphatase Inhibitors

Epithelial cell keratins make up the type I (K9–K20) and type II (K1–K8) intermediate filament proteins. In glandular epithelia, K8 becomes phosphorylated on S73 (71LLpSPL) in human cultured cells and tissues during stress, apoptosis, and mitosis. Of all known proteins, the context of the K8 S73 motif (LLS/TPL) is unique to type II keratins and is conserved in epidermal K5/K6, esophageal K4, and type II hair keratins, except that serine is replaced by threonine. Because knowledge regarding epidermal and esophageal keratin regulation is limited, we tested whether K4–K6 are phosphorylated on the LLTPL motif. K5 and K6 become phosphorylated in vitro on threonine by the stress-activated kinase p38. Site-specific anti-phosphokeratin antibodies to LLpTPL were generated, which demonstrated negligible basal K4–K6 phosphorylation. In contrast, treatment of primary keratinocytes and other cultured cells, and ex vivo skin and esophagus cultures, with serine/threonine phosphatase inhibitors causes a dramatic increase in K4–K6 LLpTPL phosphorylation. This phosphorylation is accompanied by keratin solubilization, filament reorganization, and collapse. K5/K6 LLTPL phosphorylation occurs in vivo during mitosis and apoptosis induced by UV light or anisomycin, and in human psoriatic skin and squamous cell carcinoma. In conclusion, type II keratins of proliferating epithelia undergo phosphorylation at a unique and conserved motif as part of physiological mitotic and stress-related signals.

scholarly journals Up-Dated the Critical Issues of Corneal Cross-Linking (Type-I and II): Safety Dose for Ultra-Thin Cornea, Role of Oxygen and Initiator Regeneration

2021 ◽  
Author(s):  
Jui-Teng Lin
Keyword(s):  
Steady State ◽  
Light Intensity ◽  
Transient State ◽  
Threshold Dose ◽  
Type I ◽  
Type Ii ◽  
Minimum Thickness ◽  
Increasing Function ◽  
Thin Cornea

Aims:To update analytic formulas for the overall efficacy of corneal collagen crosslinking (CXL) including both type-I and oxygen-mediated type-II mechanisms, the role of oxygen and the initiator regeneration. Study Design:modeling the kinetics of CXL in UV light and using riboflavin as the photosensitizer.Place and Duration of Study:New Taipei City, Taiwan, between June, 2021 and July, 2021.Methodology:Coupled kinetic equations are derived under the quasi-steady state condition for the 2-pathway mechanisms of CXL. For type-I CXL, the riboflavin (RF) triplet state [T] may interact directly with the stroma collagen substrate [A] to form radical (R) and regenerate initiator. For type-II process, [T] interacts with oxygen to form a singlet oxygen [1O2]. Both reactive radical (R) and [1O2], can relax to their ground state, or interact with the substrate [A]) for crosslinking. Based on a safety dose, the minimum corneal thickness formula is derived. Results:Our updated theory/modeling showed that oxygen plays a limited and transient role in the process, in consistent with that of Kamave [2]. In contrary, Kling et al [3] believed that type-II is the predominant mechanism, which however conflicting with the epi-on CXL results. For both type-I and type-II, a transient state conversion (crosslink) efficacy in an increasing function of light intensity (or dose), whereas, its steady state efficacy is a deceasing function of light intensity. RF depletion in type-I is compensated by the RF regeneration term (RGE) which is a decreasing function of oxygen. For the case of perfect regeneration case (or when oxygen=0), RF is a constant due to the catalytic cycle. Unlike the conventional Dresden rule of 400 um thickness, thin cornea CXL is still safe as far as the dose is under a threshold dose (E*), based on our minimum thickness formula (Z*). Our formula for thin cornea is also clinically shown by Hafez et al forultra thin (214 nm) CXL. Conclusion: For both type-I and type-II, a transient state conversion (crosslink) efficacy in an increasing function of light intensity (or dose), whereas, its steady state efficacy is a deceasing function of light intensity. Ultra thin cornea is still safe as far as it is under a threshold dose (E*), based on our minimum thickness formula.

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