Clinical indicators for diabetic eyecare delivered by optometrists in Australia: a Delphi study.

CLINICAL RELEVANCE: Valid and updated clinical indicators can serve as important tools in assessing and improving eyecare delivery. BACKGROUND: Indicators for diabetic eyecare in Australia were previously developed from guidelines published before 2013 and then used to assess the appropriateness of care delivery through a nationwide patient record card audit (the iCareTrack study). To reflect emerging evidence and contemporary practice, this study aimed to update clinical indicators for optometric care for people with type 2 diabetes in Australia. METHODS: Forty-five candidate indicators, including existing iCareTrack and new indicators derived from nine high-quality evidence-based guidelines, were generated. A two-round modified Delphi process where expert panel members rated the impact, acceptability, and feasibility of the indicators on a 9-point scale and voted for inclusion or exclusion of the candidate indicators was used. Consensus on inclusion was reached when the median scores for impact, acceptability, and feasibility were ≥7 and >75% of experts voted for inclusion. RESULTS: Thirty-two clinical indicators with high acceptability, impact and feasibility ratings (all median scores: 9) were developed. The final indicators were related to history taking (n = 12), physical examination (n = 8), recall period (n = 5), referral (n = 5), and patient education/communication (n = 2). Most (14 of 15) iCareTrack indicators were retained either in the original format or with modifications. New indicators included documenting the type of diabetes, serum lipid level, pregnancy, systemic medications, nephropathy, Indigenous status, general practitioner details, pupil examination, intraocular pressure, optical coherence tomography, diabetic retinopathy grading, recall period for high-risk diabetic patients without retinopathy, referral of high-risk proliferative retinopathy, communication with the general practitioner, and patient education. CONCLUSION: A set of 32 updated diabetic eyecare clinical indicators was developed based on contemporary evidence and expert consensus. These updated indicators inform the development of programs to assess and enhance the eyecare delivery for people with diabetes in Australia.

A proposed methodology for conducting a remote rigid gas permeable contact lens consultation.

PURPOSE: COVID-19 spread to numerous countries, overwhelming healthcare systems and economies worldwide. COVID-19 restrictions have prevented patients from attending consultations in person and led to the further development of telemedicine to provide health care. The situation also applies to contact lens (CL) practitioners and their patients; telemedicine enables practitioners to provide patients with regular and continuing care. This study aimed to investigate available tools to enable continuing care for rigid gas permeable (RGP) CL wearers who are unable to attend face-to-face consultations. METHODS: The study consists of three components. Firstly, an approach to enable the assessment of a patient's CL fitting and cornea remotely. Secondly, to find an affordable and reliable method to obtain a patient's visual acuity (VA), and thirdly, to develop a questionnaire to provide practitioners with information to deliver optimal patient care. RESULTS: The use of a macro lens, smartphone, and auxiliary materials enables high-quality images of the anterior eye and RGP CL to be obtained. Two free and validated smartphone applications (apps) for VA measurements were identified which are available on Android and iOS systems. Two questionnaires were also developed to enable practitioners to obtain additional patient information to facilitate optimal patient care. CONCLUSION: This study has developed the components of a remote CL consultation to enable patients who cannot attend scheduled appointments to receive care and advice to ensure the safety of their RGP CL wear. The tools involved in this study are low-cost, affordable, and an adjunct, not a substitute, for face-to-face consultations.

A Systematic Literature Review of the Career Choice of Helping Professionals Who Have Experienced Cumulative Harm as a Result of Adverse Childhood Experiences.

The pervasive effects of cumulative harm resulting from adverse childhood experiences influence all aspects of an individual's life course. Research highlights a relationship between early trauma and career choice; however, there is a dearth of research pertaining specifically to cumulative harm and the influence on career choice in the helping professions. A systematic literature review was conducted to explore the associations of cumulative harm and childhood trauma on career decision making in people in the helping professions. A search was conducted across databases between February 1990 and February 2019 relevant to searches combining three areas of interest: (a) "childhood trauma," (b) "career choice," and (c) "helping professionals." Database searches and further manual searches yielded a total of 208 articles, and 28 studies satisfied all inclusion criteria. Only studies that were peer-reviewed and published between February 1990 and February 2019 were included. The evidence from the review indicated that family of origin dysfunction, parentification, individual characteristics, and traits developed through adversity, and experiential motivations were associated with the career choice in the helping professions. Further research is required to explore different professional cohorts and the utility of life themes as both a source of data for research and reflexive practice in helping professionals.

Was Dürer 500 years ahead of science?

Brewster's dark patch is a simple optical effect in the environment. It is easily seen, but apparently it has not been formally noticed or explained until quite recently. Nevertheless, some artists appear to have represented it in paintings without, of course, knowing its optical origins. A case can be made that a watercolor by Albrecht Dürer from around 1497 illustrates the phenomenon.

A clinical method for estimating the modulus of elasticity of the human cornea in vivo.

BACKGROUND: To develop a method, using current clinical instrumentation, to estimate the Young's modulus of the human cornea in vivo. METHODS: Central corneal curvature (CCC), central corneal thickness(CCT), intraocular pressure (IOP) was measured with the Goldmann tonometer (IOPG) and the Pascal Dynamic Corneal Tonometer(PDCT) in one eye of 100 normal young human subjects (21.07 ± 2.94 years) in vivo. The Orssengo and Pye algorithm was used to calculate the Young's modulus of the corneas of these subjects. RESULTS: The Young's modulus(E) of the corneas of the subjects using the PDCT and IOPG results (Ecalc) was 0.25 ± 0.10MPa, and without the PDCT results (Eiopg) was 0.29 ± 0.06MPa. The difference in these results is due to the difference in tonometry results between the two instruments, as the mean PDCT result for the subjects was 16.89 ± 2.49mmHg and the IOPG result 15.06 ± 2.71mmHg. E was affected by the CCC of the subjects but more particularly by the CCT and IOP measurements. Corneal stiffness results are also presented. CONCLUSION: Two methods have been developed to estimate the Young's modulus of the human cornea in vivo using current clinical instrumentation. One method (Ecalc) is applicable to the general corneal condition, and Eiopg to the normal cornea, and these results can be used to calculate corneal stiffness.

Isolation and Composition Analysis of Bioactive Glycosaminoglycans from Whelk.

Glycosaminoglycans (GAGs) are found covalently attached to proteins, which create conjugates known as proteoglycans. GAGs have remarkable biological activity as co-receptors for a variety of growth factors, cytokines, and chemokines. The present study identifies the key compositional differences between the GAGs isolated from whelk and mammalian GAGs. This polysaccharide represents a new, previously undescribed GAG with cytotoxic activity on cancer cells. Disaccharides were obtained by sample digestion with heparinases I, II, and III and chondroitinase ABC. The resistant oligosaccharides from whelk GAGs treated with heparinase I, II, and III and chondroitinase ABC were retained by the filter due to their larger size. Disaccharide analysis was performed using Glycan Reduction Isotope Labeling (GRIL LCQ-MS). The amounts of filter-retained fragments, as assessed by monosaccharides analysis, suggested that a proportion of the whelk GAG chains remained resistant to the enzymes used in the disaccharide analysis. Thus, the proportions of individual disaccharide produced in this analysis may not truly represent the overall proportions of disaccharide types within the intact whelk GAGs chain. However, they do serve as important descriptors for the classification and make-up of the anti-cancer GAGs chains. Furthermore, these data represent clear evidence of the compositional differences between whelk GAGs and commercial mammalian GAGs.

Antiproliferative Activity of Glycosaminoglycan-Like Polysaccharides Derived from Marine Molluscs.

Despite the increasing availability of new classes of cancer treatment, such as immune- and targeted therapies, there remains a need for the development of new antiproliferative/cytotoxic drugs with improved pharmacological profiles that can also overcome drug resistant forms of cancer. In this study, we have identified, and characterised, a novel marine polysaccharide with the potential to be developed as an anticancer agent. Sulphated polysaccharides isolated from the common cockle (Cerastoderma edule) were shown to have antiproliferative activity on chronic myelogenous leukaemia and relapsed acute lymphoblastic leukaemia cell lines. Disaccharide and monosaccharide analysis of these marine polysaccharides confirmed the presence of glycosaminoglycan-like structures that were enriched in ion-exchange purified fractions containing antiproliferative activity. The antiproliferative activity of these glycosaminoglycan-like marine polysaccharides was shown to be susceptible to heparinase but not chondrotinase ABC digestion. This pattern of enzymatic and antiproliferative activity has not previously been seen, with either marine or mammalian glycosaminoglycans. As such, our findings suggest we have identified a new type of marine derived heparan sulphate/heparin-like polysaccharide with potent anticancer properties.

Polarization optics of the Brewster's dark patch visible on water surfaces versus solar height and sky conditions: theory, computer modeling, photography, and painting.

When the sun is near the horizon, a circular band with approximately vertically polarized skylight is formed at 90° from the sun, and this skylight is only weakly reflected from the region of the water surface around the Brewster's angle (53° from the nadir). Thus, at low solar heights under a clear sky, an extended dark patch is visible on the water surface when one looks toward the north or south quarter perpendicular to the solar vertical. In this work, we study the radiance distribution of this so-called Brewster's dark patch (BDP) in still water as functions of the solar height and sky conditions. We calculate the pattern of reflectivity R of a water surface for a clear sky and obtain from this idealized situation the shape of the BDP. From three full-sky polarimetric pictures taken about a clear, a partly cloudy, and an overcast sky, we determine the R pattern and compose from that synthetic color pictures showing how the radiance distribution of skylight reflected at the water surface and the BDPs would look under these sky conditions. We also present photographs taken without a linearly polarizing filter about the BDP. Finally, we show a 19th century painting on which a river is seen with a dark region of the water surface, which can be interpreted as an artistic illustration of the BDP.

Preliminary identification of differentially expressed tear proteins in keratoconus.

PURPOSE: To examine the proteins differentially expressed in the tear film of people with keratoconus and normal subjects. METHODS: Unstimulated tears from people with keratoconus (KC) and controls (C) were collected using a capillary tube. Tear proteins from people with KC and controls were partitioned using a novel in-solution electrophoresis, Microflow 10 (ProteomeSep), and analyzed using linear ion trap quadrupole fourier transform mass spectrometry. Spectral counting was used to quantify the individual tear proteins. RESULTS: Elevated levels of cathepsin B (threefold) were evident in the tears of people with KC. Polymeric immunoglobulin receptor (ninefold), fibrinogen alpha chain (eightfold), cystatin S (twofold), and cystatin SN (twofold) were reduced in tears from people with KC. Keratin type-1 cytoskeletal-14 and keratin type-2 cytoskeletal-5 were present only in the tears of people with KC. CONCLUSIONS: The protein changes in tears, that is, the decrease in protease inhibitors and increase in proteases, found in the present and other previously published studies reflect the pathological events involved in KC corneas. Further investigations into tear proteins may help elucidate the underlying molecular mechanisms of KC, which could result in better treatment options.

Effects of eye rubbing on the levels of protease, protease activity and cytokines in tears: relevance in keratoconus.

BACKGROUND: Proteases, protease activity and inflammatory molecules in tears have been found to be relevant in the pathogenesis of keratoconus. We sought to determine the influence of eye rubbing on protease expression, protease activity and concentration of inflammatory molecules in tears. METHODS: Basal tears were collected from normal volunteers before and after 60 seconds of experimental eye rubbing. The total amount of matrix metalloproteinase (MMP)-13 and inflammatory molecules interleukin (IL)-6 and tumour necrosis factor (TNF)-α in the tear samples were measured using specific enzyme-linked immunosorbent assays (ELISA). Tear collagenase activity was investigated using a specific activity assay. RESULTS: The concentrations of MMP-13 (51.9 ± 34.3 versus 63 ± 36.8 pg/ml, p = 0.006), IL-6 (1.24 ± 0.98 versus 2.02 ± 1.52 pg/ml, p = 0.004) and TNF-α (1.16 ± 0.74 versus 1.44 ± 0.66 pg/ml, p = 0.003) were significantly increased in normal subjects after eye rubbing. The experimental eye rub did not alter significantly the collagenase activity (5.02 ± 3 versus 7.50 ± 3.90 fluorescent intensity units, p = 0.14) of tears. CONCLUSION: Eye rubbing for 60 seconds increased the level of tear MMP-13, IL-6 and TNF-α in normal study subjects. This increase in protease, protease activity and inflammatory mediators in tears after eye rubbing may be exacerbated even further during persistent and forceful eye rubbing seen in people with keratoconus and this in turn may contribute to the progression of the disease.

Correction factors for Goldmann Tonometry.

PURPOSE: The purpose of the study was to evaluate the in vitro accuracy of correction factors in decreasing the error in the intraocular pressure (IOP) measurements obtained using the Goldmann Applanation Tonometer (GAT). METHODS: Nineteen donor corneas, from individuals aged between 57 and 99 years (mean 75.7 years, standard deviation±11.4 years) were subjected to posterior pressure simulating in vivo true IOP (IOPT) using an inflation test rig. Central corneal thickness and corneal curvature were measured. The posterior pressure was set at 25 different pressure levels between 5 and 45 mm Hg and IOP was measured using the GAT. Five different correction equations were applied to the IOP measurements obtained using the GAT to determine corrected IOP. The multiparameter correction equations applied were derived by Elsheikh, Ehlers, Chihara, Shimmyo et al, and Orssengo and Pye. The differences between IOPT and the IOP measured using the GAT were recorded as uncorrected errors, whereas the differences between IOPT and each of the corrected IOP were the tonometry errors after correction. RESULTS: The mean and standard deviation of error in tonometry before correction was +2.25±0.62 mm Hg. The mean errors in tonometry after correction using the Elsheikh and Chihara equations were +0.78±0.62 and +1.08±0.61 mm Hg, respectively. The mean errors in tonometry for the Ehlers, Shimmyo et al, and Orssengo and Pye equations were negative, indicating an overcorrection; the values were -0.75±2.28, -1.27±1.85, and -0.77±1.83 mm Hg, respectively. CONCLUSIONS: The Elsheikh and the Chihara et al's equations considerably decreased error in IOP measurements obtained by the GAT when compared with IOPT and were more consistent than other correction equations. The 2 equations may be of clinical utility in obtaining estimates of IOPT.

Associations between diurnal changes in Goldmann tonometry, corneal geometry, and ocular response analyzer parameters.

PURPOSE: To investigate the possible covariations between diurnal changes in Goldmann applanation tonometry (GAT) estimates of intraocular pressure (IOP), central corneal thickness (CCT), central corneal radius, and ocular response analyzer measures of corneal hysteresis and corneal resistance factor (CRF). METHODS: Twenty-five healthy normal subjects (age, 21 ± 2 years) had central corneal radius, ocular response analyzer, GAT, and CCT measurements performed in 1 eye at multiple times for more than 24 hours. Measurements were taken at 17:00 and repeated every 2 hours until 23:00. Subjects then slept uninterrupted overnight for approximately 8 hours. On awakening, readings were taken at a 20-minute frequency from 7:00 to 9:00 inclusive, followed by 2 hourly intervals until 17:00. RESULTS: The maximum variation in GAT for more than 24 hours was 2.5 mm Hg, and these fluctuations were predicted by the diurnal variations of CCT (0.37 mm Hg ΔGAT/10 µm CCT, P < 0.01) and CRF (0.68 mm Hg ΔGAT/mm Hg CRF, P < 0.01). The diurnal changes in corneal hysteresis and CRF both covaried with those of CCT (0.16 and 0.30 mm Hg/10 µm ΔCCT, respectively, both Ps < 0.01). None of these associations was statistically different during and after the nominal period of resolution from overnight corneal swelling (2-way interactions, all Ps > 0.05). CONCLUSIONS: If the IOP is assumed to be independent of corneal parameters, the clinically significant 24-hour variation in GAT being partially predicted by the changes in CCT and CRF suggests that the diurnal variation in corneal parameters affects tonometry measurements. CRF may also be dependent on the level of IOP.

Proteases, proteolysis and inflammatory molecules in the tears of people with keratoconus.

PURPOSE: To investigate the expression of proteases, proteolytic activity and cytokines in the tear film of people with keratoconus. METHODS: Basal tears from people with keratoconus, from individuals who had undergone corneal collagen cross-linking for the treatment of keratoconus, and from normal controls were collected using a capillary tube. Corneal curvature of each subject was mapped. The total protein in tears was estimated. Levels and activity of proteases in the tears were analysed using specific antibody arrays and activity assays. RESULTS: The total tear protein level was significantly reduced in keratoconus (4.1 ± 0.9 mg/ml) compared with normals (6.7 ± 1.4 mg/ml) (p < 0.0001) or subjects who had undergone corneal collagen cross-linking (5.7 ± 2.3 mg/ml) (p < 0.005). Significantly (p < 0.05) increased tear expression of matrix metalloproteinases (MMP) -1, -3, -7, -13, interleukins (IL) -4, -5, -6, -8 and tumour necrosis factor (TNF) -α, -ß were evident in keratoconus. Tear IL-6 was the only cytokine significantly (p < 0.05) increased in tears of keratoconus subjects compared with the collagen cross-linked group. No significant difference in tear proteases were observed between the normal and the cross-linked groups, although the expression of TNF-α was significantly (p < 0.05) increased in the cross-linked group compared with the controls. Elevated gelatinolytic (87.5 ± 33.6 versus 45.8 ± 24.6 FIU, p < 0.0001) and collagenolytic (6.1 ± 3.2 versus 3.6 ± 2.0 FIU, p < 0.05) activities were observed in tears from keratoconus compared with normal subjects. The activity of tear gelatinases (69.6 ± 22.2 FIU) and collagenases (5.7 ± 3.3 FIU) in the collagen cross-linked group was not significantly different compared with either keratoconus or normals. CONCLUSION: Tears of people with keratoconus had 1.9 times higher levels of proteolytic activity and over expression of several MMPs and cytokines compared with tears from controls. Further investigations are required to study the possible implications of these changes and whether they can be used to monitor disease progression or determine the success of corneal collagen cross-linking.

Levels of lactoferrin, secretory IgA and serum albumin in the tear film of people with keratoconus.

Keratoconus is a degenerating disease of the eye which causes an irregularly shaped cornea leading to severe impairment of vision. Tear proteomics in keratoconus has been a topic of substantial discussion and speculation over many years. This study was designed to examine the levels of total protein, lactoferrin, secretory IgA and serum albumin in the tear film of people with keratoconus. Basal tears were collected using a capillary tube and corneal curvature was mapped using a topographer. Total protein in tears was estimated. The amount of regulated protein lactoferrin, constitutive protein sIgA and serum protein albumin was measured using specific ELISAs. The changes in protein concentrations in tears were correlated to the degree of corneal asphericity. There was a two-fold (p<0.0001) decrease in total protein levels between keratoconus (3.86 ± 1.62 mg/ml) and normal (7.00 ± 1.58 mg/ml) tears. The amount of lactoferrin (0.67 ± 0.28 vs. 1.13 ± 0.29 mg/ml) and secretory IgA (0.78 ± 0.36 vs. 1.70 ± 0.66 mg/ml) were significantly (p<0.0001) reduced in keratoconus tears. Variation in serum albumin levels between keratoconus (8.18 ± 4.72 µg/ml) and normal tears (11.66 ± 8.20 µg/ml) were not significant. The differences in total protein, lactoferrin and secretory IgA were not associated with contact lens wear, age, gender or atopy of subjects. The keratometry reading was negatively correlated to tear levels of total protein (r = -0.59, p < 0.01) lactoferrin (r = -0.40, p < 0.05) and secretory IgA (r = -0.34, p < 0.05). The tears of keratoconus subjects appear to have an altered protein profile, and one that might change with the severity of the disease. These findings may lead the way to understanding or monitoring disease progression.

Changes in corneal biomechanics and applanation tonometry with induced corneal swelling.

PURPOSE: To investigate the changes in Goldmann applanation tonometry (GAT) and Ocular Response Analyzer (ORA) measurements with corneal edema induced by contact lenses. METHODS: Twenty-five healthy, normal subjects (age, 23 ± 2 years) had central corneal radius (CCR), ORA, GAT, and central corneal thickness (CCT) measurements performed in both eyes before a thick, soft hydrogel contact lens was worn with eye closure for 2 hours in one eye. Measurements were repeated immediately after lens removal and every 20 minutes thereafter for the following hour. RESULTS: The experimental and control eyes behaved asymmetrically over time (repeated measures analysis of variance [RMANOVA]; P < 0.05) for all variables except CCR. GAT, ORA Goldmann-correlated intraocular pressure (ORAg), and ORA corneal-compensated intraocular pressure (ORAcc) showed comparable overestimations, whereas corneal hysteresis (CH) and corneal resistance factor (CRF) responded to corneal swelling in dissimilar ways (RMANOVA; α = 0.05). The variation in GAT in experimental eyes could be predicted by changes in CRF (0.85 [0.23] mm Hg ΔGAT/mm Hg ΔCRF; P < 0.001), but not by CCT or CH. The covariation of both CH and CRF with CCT was influenced by the presence of corneal swelling (Eye×ΔCCT interaction, P < 0.001 and P = 0.003, respectively). CONCLUSIONS: The GAT overestimation caused by small amounts of corneal swelling represents an overall increase in corneal rigidity, which is partially characterized by CRF. In contrast, CH does not appear to usefully quantify biomechanical changes induced by corneal swelling. The accuracy of ORAcc is affected by corneal swelling.

A clinical description of Ocular Response Analyzer measurements.

PURPOSE: To examine the interrelationships among the Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments, Buffalo, NY), Goldmann applanation tonometer (GAT), and corneal geometry measurements in a young, healthy sample. METHODS: Central corneal radius, ORA, GAT, and central corneal thickness (CCT) measurements were taken in 99 subjects (age, 21 ± 2 years) who were free of ocular and systemic disease. RESULTS: The mean ± SD corneal hysteresis (CH) and corneal resistance factor (CRF) were 10.4 ± 1.2 and 10.1 ± 1.5 mm Hg, respectively. The Bland-Altman 95% limits of agreement of ORA Goldmann-correlated IOP (ORAg) and ORA corneal-compensated (ORAcc) IOP with reference to GAT were -4.5 to +6.0 and -4.1 to +6.8 mm Hg, respectively. The full equations used by the ORA to calculate ORAcc and CRF were reconstructed. The statistically significant effect of CCT on GAT became redundant if CRF was included in a multivariate regression analysis. Both CH and CRF were associated with CCT (R(2) = 0.252 and 0.290, respectively). CONCLUSIONS: Sample CH and CRF were consistent with those reported in the literature. ORAg and ORAcc agreed poorly with GAT. CRF appears to be at least a partial description of corneal rigidity. The ocular determinants of CH are unclear.

Are proteinases the reason for keratoconus?

PURPOSE: Keratoconus is a degenerating disease of the eye that results in an irregularly-shaped cornea. The etiology of the disease is unknown and the prognosis is difficult due to the variability in outcome. Keratoconus has been associated with eye rubbing, atopy, contact lens wear, as well as genetic conditions, such as Down's syndrome, Ehlers-Danlos syndrome, and Marfan's syndrome. Thinning of the cornea in keratoconus has been well studied and is documented to occur as a result of degradation of corneal collagen. The reason for this tissue degradation is unknown but has been hypothesized to be linked with proteases. METHODS: This study used a literature search to review the role of proteases and inflammatory molecules in the aetiology of keratoconus. RESULTS: Early studies demonstrated elevated levels of collagenolytic and gelatinolytic activities in laboratory cultures of keratoconic corneas. Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteins that include collagenases and gelatinases. MMPs levels are altered in keratoconus corneas compared to normal corneas and the level of tissue inhibitor of metalloproteinases-1 (TIMP-1) is decreased in keratoconic corneas. Recent studies have demonstrated the involvement of Cathepsin B, G, and K in keratoconus. Although thought to be a non-inflammatory disease, inflammatory molecules, such as interleukins and tumor necrosis factor have been shown to be elevated in keratoconus, and these inflammatory molecules may mediate production and activation of proteases. CONCLUSIONS: Proteases may be implicated in keratoconus. An in-depth investigation of these proteases may help in better understanding the course of the disease.

Goldmann tonometry correction factors based on numerical analysis.

With the world's aging population, it is expected that the number of people affected by glaucoma, the second most common cause of irreversible blindness, will increase considerably. Current knowledge on glaucoma progression relates elevation of the intraocular pressure (IOP) to optic nerve damage and hence visual impairment. For this reason, IOP measurement in tonometry has become an essential part of routine eye examinations needed for the diagnosis and management of the disease. The accuracy of the current reference standard in tonometry, the Goldmann applanation tonometer, is known to be affected by the natural variations in corneal thickness, curvature, and material properties. Earlier studies attempted to quantify these effects and produced correction factors that considered the variations in each one of these parameters separately, and no guidance was given as to how to combine the effects of variations in more than one parameter. The present research attempted to address this gap by conducting a multidimensional numerical study that considered variations in thickness, curvature, material properties, and IOP, and used the results to develop a single correction equation that considered these parameters simultaneously. The results of the analysis and the correction equation were validated successfully against the outcome of earlier clinical and mathematical studies on the effect of individual parameters, and the correction equation was presented in a simple form suitable for clinical application.

Structural studies of heparan sulfate hexasaccharides: new insights into iduronate conformational behavior.

There is a growing opinion that the conformational dynamics within HS chains is critical to their observed biological activities. Investigations into HS conformational dynamics are problematic, given the structural complexity and heterogeneity of HS chains. However, this goal will be more obtainable once we understand the important roles HS sequence/sulfation patterns play in determining the conformational dynamics of iduronate units. This is the first study to compare isomers of N-sulfated oligosaccharides, with respect to the conformational versatility of their internal iduronates. Characterization by NMR spectroscopy of two HS oligosaccharides derived from porcine mucosal HS enabled the measurement of iduronate coupling constants, while under the influence of different flanking saccharide sequences. By fitting our coupling constant data to a new set of theoretical coupling constants, calculated using explicit water molecular dynamic simulations, we are able to offer new insights into the role sequence/sulfation patterns play in influencing iduronate conformational behavior. Fitting of experimental data, using our new theoretically derived coupling constants, suggests that replacement of the N-sulfate group to the reducing side of IdoUA by an N-acetyl group has little effect on the balance of IdoUA conformational equilibrium. Fitting of coupling constants for sequences GlcNS-IdoUA(2S)-GlcNS and GlcNS(6S)-IdoUA(2S)-GlcNS suggests that the flanking 6-O-sulfate group alters the balance of the IdoUA(2S) equilibrium more toward the (2)S0 conformation. There is also the suggestion that a cooperative effect may exist for N- and 6-O sulfation. These observations could be the key to understanding the important regulatory function attributed to 6-O-sulfation within HS chains.