Microvascular complications in orthokeratology (Ortho-K): A real-time study on the microvasculature of the bulbar conjunctiva in Ortho-K treatment.

Orthokeratology (Ortho-K) is an over-night hard contact lens therapy, which physically reshapes the corneal curvature in order to stabilize or temporally eliminate myopia in patients. We hypothesize that the prolonged physical contact and mechanical pressure induced by the Ortho-K lenses may create lasting inadvertent effects and damages (microangiopathy), and may bring about unwanted changes in the microvasculature of the bulbar conjunctiva. Computer-assisted intravital microscopy (CAIM) was used to view, document (via videotaping) and objectively quantify (via computer-assisted image analysis) the real-time dynamic and morphometric characteristics of the conjunctival microcirculation in long-term (at least over one year) Ortho-K patients (n = 11) and matched non-user control subjects (n = 8). Ortho-K patients were instructed to wear their lenses overnight following standard protocol. During the study, the conjunctival microcirculation of the left eye of all Ortho-K lens users was viewed, frequently re-focused and videotaped, without and with the lens in place, as outlined in Methods. The matched control subjects (non-lens wearing) were videotaped and studied in like manner. The dynamic and morphometric characteristics of each user and control subject were analyzed, quantified and summated as a severity index (SI) collectively for comparison. SI of Ortho-K lens users (4.18±1.08) differed significantly from SI of control subjects (1.75±1.39, p≤0.05). In addition, changes in the conjunctival microcirculation (e.g., flow velocity, vessel diameter, shape change, etc) were viewed and videotaped immediately after the myopic patients put on the Ortho-K lenses. Eight of the 11 Ortho-K lens users displayed significant percentage changes (p≤0.05) in flow velocity and 10 of 11 displayed significant percentage changes (p≤0.05) in vessel diameter, without and with the Ortho-K lenses. The results clearly indicated that significant microvascular changes via tissue remodeling occurred, and were caused directly by the physical presence of the Ortho-K lenses.

Determination of Green's function for three-dimensional traction force reconstruction based on geometry and boundary conditions of cell culture matrices.

Cell migration plays a particular important role in the initiation and progression of many physical processes and pathological conditions such as tumor invasion and metastasis. Three-dimensional traction force microscopy (TFM) of high resolution and high accuracy is being developed in an effort to unveil the underlying mechanical process of cell migration in a vivo-like environment. Linear elasticity-based TFM (LETM) as a mainstream approach relies on the Green's function (that relates traction forces to matrix deformation), of which the inherent boundary conditions and geometry of the matrix could remarkably affect the result as suggested by previous 2D studies. In this study, we investigated this close linkage in 3D environment, via modeling of a cell sensing a close-by fixed boundary of a 3D matrix surrounding it, and comparing the reconstructed traction forces from three different solutions of the Green's function, including a fully matching solution derived using the adapted Mindlin's approach. To increase fidelity in the estimate of traction forces for extreme conditions such as a sparse sampling of deformation field or targeting small focal adhesions, we numerically solved the singularity problem of the Green's function in a non-conventional way to avoid exclusion of singular point regions that could contain representative deformation indicators for such extreme conditions. A single case experimental study was conducted for a multi-cellular structure of endothelial cells that just penetrated into the gel at the early stage of angiogenesis. STATEMENT OF SIGNIFICANCE: This study focused on the fundamental issue regarding extension of linear elasticity-based TFM to deal with physically realistic matrices (where cells are encapsulated), which concerns determination of the Green's function matching their geometry and boundary conditions. To increase fidelity in the estimate of traction forces for extreme conditions such as a sparse sampling of deformation field or targeting small focal adhesions, we numerically solved the singularity problem of the Green's function to avoid exclusion of singular point regions that could contain representative deformation indicators for such extreme conditions. The proposed approach to adapting the Green's function for the specific 3D cell culture situation was examined in a single case experimental study of endothelial cells in sprouting angiogenesis.

Real-time studies of hypertension using non-mydriatic fundus photography and computer-assisted intravital microscopy.

Hypertension is asymptomatic until late stages of pathogenesis, rendering an effective means of detection for early diagnosis essential. The current method of diagnosing hypertension requires two or more sphygmomanometric readings over two or more office visits, which potentially hinders early detection. Though retinopathy is an indicator of vascular damage, it generally presents in later stages of hypertension. Previous and related studies have suggested that the microvasculature in the bulbar conjunctiva may be a sensitive site to assess vasculopathy. Conjunctival microangiopathy was assessed using CAIM and reported on a severity index (SI). Images of the retinal fundus were taken via non-mydriatic fundus photography and graded using the Scheie scale in the same subjects to compare with CAIM. Conjunctival microangiopathy was significantly elevated in hypertensive subjects (SI = 5.35 ± 1.04, n = 20) compared to control subjects (SI = 1.75 ± 1.39, n = 8; p ≤ 0.05), and correlated with time since disease diagnosis (R² = 0.33). Hypertensive subjects with Grade 1 retinopathy displayed increased conjunctival microangiopathy (SI = 5.85 ± 0.90, n = 13) compared to those without retinopathy (SI = 4.43 ± 0.53, n = 7; p ≤ 0.05). These data indicate a possible pre-retinopathy time window during which conjunctival microangiopathy may indicate the risk of organ damage, supporting the hypothesis that the conjunctival microcirculation may serve as a platform for early detection and monitoring disease progression.

Microvascular abnormalities in the bulbar conjunctiva of contact lens users.

Soft contact lenses are commonly used to improve vision acuity or in cosmetic enhancement. We hypothesize that contact lens use can cause inadvertent damage to either the conjunctival microcirculation via direct vasoocclusion when the lens physically interacts with or damages the underlying vessels, or to the bulbar conjunctiva itself when the lens rests unevenly on the surface of the bulbar conjunctiva. Computer-assisted intravital microscopy was utilized to document (via video recording) and objectively quantify (via image analysis) real-time microvascular abnormalities resulting from changes and vessel remodeling in the conjunctival microcirculation in long-term (>2 yrs) contact lens users (n = 102), with non-users serving as control subjects (n = 29). A severity index (SI)--computed as the arithmetic sum of the abnormalities found in the conjunctival microcirculation in each contact lens user--was established for objective comparison with control subjects and critical interpretation. Contact lens user SI was significantly higher than control SI (user = 6.21 ± 1.26; control = 2.31 ± 1.49; p < 0.05), indicative of severe vasculopathy arising from contact lens use. The users also had significantly wider conjunctival vessel diameter (user = 71.25 ± 12.09 µm; control = 52.20 ± 5.10 µm; p < 0.05). Additional abnormalities, including damaged vessels, hemosiderin deposits (from damaged vessels or injury to the surface of the bulbar conjunctiva), vessel sludging, intermittent blood flow, and vessel tortuosity were commonly found in or adjacent to locations where the contact lens physically rested on the underlying conjunctival vessels. These results strongly suggest that microvascular abnormalities and remodeling changes occurred as a result of the inadvertent physical interaction of the lenses with either the underlying conjunctival vessels or the surface of the bulbar conjunctiva in contact lens users.

Non-invasive prediction of skin flap shrinkage: a new concept based on animal experimental evidence.

A non-invasive, in vivo method has been developed to predict the skin flap shrinkage (retraction) following a harvest. It involves the use of a novel custom-designed extensometer to measure the force-displacement behaviour of skin and subsequent data analysis to estimate the shrinkage. In validation experiments performed on pigs, this method has been shown to produce results with an average absolute error of 6.0% between the actual and predicted shrinkages. This may be close to what an experienced surgeon would estimate subjectively, thus indicating the potential usefulness of this method to predict flap shrinkage of patient's donor sites.

New extensometer to measure in vivo uniaxial mechanical properties of human skin.

Biomechanical properties of skin are important for clinical decision making as well as clinical intervention. Measuring these properties in vivo is critical for estimating dimensional behaviour of skin flap or graft after harvest. However, existing methodologies and devices often suffer from lack of standardisation and unwanted peripheral force contribution due to the deformation of surrounding tissues during measurement. This naturally leads to measurement inaccuracies and lack of reproducibility. In order to improve the measurement accuracy, a new portable extensometer, which measures the non-invasive in vivo biomechanical properties of skin, has been designed and constructed. This design incorporates three pads that attach to the skin, including a C-shaped pad to shield the force sensor from peripheral forces. Such design produces data that are significantly closer to in vitro measurements. The results have been verified by finite element analysis, and experiments on rubber sheets and pig skins. This device can be used to obtain biomechanical properties of skin that will aid doctors in measuring skin elasticity and surgical planning, especially in skin flap surgery.

Menstruation among adolescent girls in Malaysia: a cross-sectional school survey.

INTRODUCTION: The onset of menstruation is part of the maturation process. However, variability in menstrual cycle characteristics and menstrual disorders are common. The purpose of this study was to determine the menstrual characteristics of adolescent females and factors associated with it. METHODS: This is a cross-sectional descriptive study carried out on 2,411 secondary school adolescent females in Negeri Sembilan, Malaysia. Data were collected using a self-administered structured questionnaire on menstruation in Bahasa Malaysia. RESULTS: Abnormal cycle length (menstrual cycle longer than 35 days or cycle length between 14 to 20 days or irregular pattern) was common and affected 37.2 percent of subjects. The majority (74.6 percent) experienced premenstrual syndrome and 69.4 percent had dysmenorrhoea. About 18 percent reported excessive menstrual loss (use two pads at a time to prevent blood from soaking through or confirmed by doctor to be anaemic due to heavy menstrual flow). Only 11.1 percent of schoolgirls seeked medical consultation for their menstrual disorders. Mothers remained the most important source of information (80 percent). Menstrual disorders were significantly more common in female adolescents who smoke and have suicidal behaviours (p-value is less than 0.05). CONCLUSION: Menstrual problems among adolescent female are common. They are influenced by certain modifiable factors.

Premarital sexual intercourse among adolescents in Malaysia: a cross-sectional Malaysian school survey.

INTRODUCTION: Sexual intercourse among Malaysian adolescents is a major concern, especially with the worry of HIV/AIDS. This study was done to determine the prevalence of sexual intercourse among secondary school students aged 12 to 19 years in Negeri Sembilan, Malaysia. METHODS: This is a cross-sectional school survey conducted on 4,500 adolescent students based on a structured questionnaire. Data were collected using the self-administered questionnaire (translated version of the Youth Risk Behaviour Surveillance in Bahasa Malaysia). RESULTS: The study showed that 5.4 percent of the total sample were reported to have had sexual intercourse. The proportion among male students who had had sex was higher (8.3 percent) compared with female students (2.9 percent). The mean age at first sexual intercourse was 15 years. One percent of students reported that they had been pregnant or had made someone else pregnant. Adolescent sexual intercourse was significantly associated with (1) socio-demographical factors (age, gender); (2) environmental factors (staying with parents); and (3) substance use (alcohol use, cigarette smoking, drug use), even after adjustment for demographical factors. The survey showed that 20.8 percent of respondents had taken alcohol, 14.0 percent had smoked cigarettes, 2.5 percent had tried marijuana, 1.2 percent had tried ecstasy pills, 2.6 percent had tried glue sniffing, 0.7 percent had tried heroin, and 0.7 percent had intravenous drugs. CONCLUSION: Prevalence of sexual intercourse among Malaysian adolescents was relatively low compared to developed countries. However, certain groups of adolescents tend to be at higher risk of engaging in sexual intercourse. This problem should be addressed early by targeting these groups of high-risk adolescents.