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 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.

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 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 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 Unified Theory for Hybrid-Photocatalysts: A Review on New Strategies for Synergic, Enhanced Conversion Efficacy and Photoredox Cycle

2021 ◽  
Author(s):  
Jui-Teng Lin
Keyword(s):  
Steady State ◽  
Light Intensity ◽  
Polymer Network ◽  
Transient State ◽  
Functional Materials ◽  
State Dependence ◽  
Comprehensive Model ◽  
Effective Absorption Coefficient ◽  
Theoretical Predictions ◽  
Reported Data

This article presents, for the first time, comprehensive model based on the proposed mechanism of Rahal et al [17], Bonardi {20], Tar et al [20], and Mau et al [24], for 3-component systems of G1/Iod/EDB, G1/Iod/amine (in gold chloride), and Iod/Benzoic/Borate (for reduced oxygen inhibition) for the hybri free radical (FRP) and cationic (CP) photopolymerization of interpenetrated polymer network (IPN) systems. Analytic formulas are developed to explore the new features including: (i) conversion efficacy(CE) of FRP is an increasing function of the light intensity (I), the effective absorption coefficient (b), for transient state, whereas, CE at steady-state is independent to the light intensity; (ii) initiator regeneration (RGE)
provides a catalytic cycle for improved CE for FRP and CP; (iii) in the IPN system, the synergic effects due to the co-exist of FRP and CP include: (i) CP can increase the medium viscosity limiting the diffusional oxygen replenishment, such that OIH is reduced; (ii) the cationic monomer also acts as a diluting agent for the radical polymer network, and (iii) the exothermic property of the CP polymerization. We have proposed ascaling law for the transient and steady-state dependence of CE on the key parameter P=bIC0, given by a an m-order power law of Pm, with m = 0.5 to 1.5, depending on various conditions. The CE also has an optimal value for maximum CE. The presented comprehensive model (with minimum mathematics) focusing on the enhancement mechanisms/pathways, provides analytic formulas which can be used to analyze reported data, and, more importantly, serves as guidance for exploring new functional materials or new kinetic schemes for improved conversion or procedures for both industrial and medical applications such as additive manufacturing (AM), 3D and 4D bioprinting. Finally, we have proposed new directions/experiments based on our theoretical predictions.

Effects of KCNQ channel blockers on K+ currents in vestibular hair cells

2001 ◽  
Vol 280 (3) ◽  
pp. C473-C480 ◽  
Author(s):  
Katherine J. Rennie ◽  
Tianxiang Weng ◽  
Manning J. Correia
Keyword(s):  
Steady State ◽  
Hair Cells ◽  
Low Voltage ◽  
Dissociation Constants ◽  
Channel Blockers ◽  
Type I ◽  
Type Ii ◽  
Kcnq Channels ◽  
Vestibular Hair Cells ◽  
Inward Currents

Linopirdine and XE991, selective blockers of K+ channels belonging to the KCNQ family, were applied to hair cells isolated from gerbil vestibular system and to hair cells in slices of pigeon crista. In type II hair cells, both compounds inhibited a slowly activating, slowly inactivating component of the macroscopic current recruited at potentials above −60 mV. The dissociation constants for linopirdine and XE991 block were <5 μM. A similar component of the current was also blocked by 50 μM capsaicin in gerbil type II hair cells. All three drugs blocked a current component that showed steady-state inactivation and a biexponential inactivation with time constants of ∼300 ms and 4 s. Linopirdine (10 μM) reduced inward currents through the low-voltage-activated K+ current in type I hair cells, but concentrations up to 200 μM had little effect on steady-state outward K+ current in these cells. These results suggest that KCNQ channels may be present in amniote vestibular hair cells.

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.

Extracellular matrix synthesis and turnover by type II pulmonary epithelial cells

1992 ◽  
Vol 262 (5) ◽  
pp. L582-L589 ◽  
Author(s):  
D. E. Rannels ◽  
S. E. Dunsmore ◽  
R. N. Grove
Keyword(s):  
Extracellular Matrix ◽  
Steady State ◽  
Epithelial Cells ◽  
Primary Cultures ◽  
Calf Serum ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Pulmonary Epithelial Cells ◽  
Type Ii Cell

Both type I and type II pulmonary epithelial cells contact the extracellular matrix (ECM). Type II cell-ECM interactions are bidirectional; they involve matrix-mediated modulation of type II cell differentiation, as well as cellular synthesis and deposition of ECM components. The present experiments examine the kinetics of accumulation of newly synthesized proteins in cell and matrix fractions from primary cultures of type II pneumocytes. Cycloheximide-sensitive incorporation of [3H]leucine into total protein of both the cell and ECM fractions was linear for 24–30 h, when steady-state labeling was reached and maintained to at least day 8. Over this interval, the cells enlarged but did not divide. Newly synthesized proteins recovered in the matrix fraction averaged 1–2% of those in the cells. Relative rates of radiolabeling of matrix proteins peaked at culture day 2 and increased in the absence of serum. In short-pulse studies, initial rates of protein synthesis were equal on culture days 1 and 3; this suggested that the steady-state labeling kinetics above reflected protein turnover. This was supported by rapid loss of radioactivity from the ECM after fresh type II cells were seeded on a prelabeled, cell-free matrix surface. Fresh or conditioned Dulbecco's modified Eagle's medium containing 10% fetal calf serum had little effect on matrix stability. These results demonstrate regulated deposition and turnover of a complex ECM by type II cells and provide a basis for further investigations of factors that control these processes.

scholarly journals Excitability and Threshold Mechanism for Enhanced Neuronal Response Induced by Inhibition Preceding Excitation

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Hanqing Ma ◽  
Bing Jia ◽  
Yuye Li ◽  
Huaguang Gu
Keyword(s):  
Steady State ◽  
Neuronal Response ◽  
Inhibitory Effect ◽  
Type I ◽  
Type Ii ◽  
Neural Firing ◽  
Firing Activity ◽  
Subthreshold Oscillations ◽  
Auditory Nervous System ◽  
Threshold Mechanism

Postinhibitory facilitation (PIF) of neural firing presents a paradoxical phenomenon that the inhibitory effect induces enhancement instead of reduction of the firing activity, which plays important roles in sound location of the auditory nervous system, awaited theoretical explanations. In the present paper, excitability and threshold mechanism for the PIF phenomenon is presented in the Morris-Lecar model with type I, II, and III excitabilities. Firstly, compared with the purely excitatory stimulations applied to the steady state, the inhibitory preceding excitatory stimulation to form pairs induces the firing rate increased for type II and III excitabilities instead of type I excitability, when the interval between the inhibitory and excitatory stimulation within each pair is suitable. Secondly, the threshold mechanism for the PIF phenomenon is acquired. For type II and III excitabilities, the inhibitory stimulation induces subthreshold oscillations around the steady state. During the middle and ending phase of the ascending part and the beginning phase of the descending part within a period of the subthreshold oscillations, the threshold to evoke an action potential by an excitatory stimulation becomes weaker, which is the cause for the PIF phenomenon. Last, a theoretical estimation for the range of the interval between the inhibitory and excitatory stimulation for the PIF phenomenon is acquired, which approximates half of the intrinsic period of the subthreshold oscillations for the relatively strong stimulations and becomes narrower for the relatively weak stimulations. The interval for the PIF phenomenon is much shorter for type III excitability, which is closer to the experiment observation, due to the shorter period of the subthreshold oscillations. The results present the excitability and threshold mechanism for the PIF phenomenon, which provide comprehensive and deep explanations to the PIF phenomenon.

scholarly journals Behavior of oxygen saturation and blood filling in the venous capillary system of the biceps brachii muscle during a fatiguing isometric action

2020 ◽  
Vol 30 (1) ◽  
pp. 79-87 ◽  
Author(s):  
Silas Dech ◽  
Frank Bittmann ◽  
Laura Schaefer
Keyword(s):  
Steady State ◽  
Oxygen Saturation ◽  
Biceps Brachii ◽  
Rank Correlation ◽  
Type I ◽  
Type Ii ◽  
Venous Oxygen Saturation ◽  
Capillary Circulation ◽  
Muscle Actions ◽  
Isometric Muscle

The objective of the study is to develop a better understanding of the capillary circulation in contracting muscles. Ten subjects were measured during a submaximal fatiguing isometric muscle action by use of the O2C spectrophotometer. In all measurements the capillary-venous oxygen saturation of hemoglobin (SvO2) decreases immediately after the start of loading and levels off into a steady state. However, two different patterns (type I and type II) emerged. They differ in the extent of deoxygenation (–10.37 ±2.59 percent points (pp) vs. –33.86 ±17.35 pp, P = .008) and the behavior of the relative hemoglobin amount (rHb). Type I reveals a positive rank correlation of SvO2 and rHb (ρ = 0.735, P <.001), whereas a negative rank correlation (ρ = –0.522, P <.001) occurred in type II, since rHb decreases until a reversal point, then increases averagely 13% above the baseline value and levels off into a steady state. The results reveal that a homeostasis of oxygen delivery and consumption during isometric muscle actions is possible. A rough distinction in two types of regulation is suggested.

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