Guided Tissue Regeneration in Heart Valve Replacement: From Preclinical Research to First-in-Human Trials

Heart valve tissue-guided regeneration aims to offer a functional and viable alternative to current prosthetic replacements. Not requiring previous cell seeding and conditioning in bioreactors, such exceptional tissue engineering approach is a very fascinating translational regenerative strategy. After in vivo implantation, decellularized heart valve scaffolds drive their same repopulation by recipient’s cells for a prospective autologous-like tissue reconstruction, remodeling, and adaptation to the somatic growth of the patient. With such a viability, tissue-guided regenerated conduits can be delivered as off-the-shelf biodevices and possess all the potentialities for a long-lasting resolution of the dramatic inconvenience of heart valve diseases, both in children and in the elderly. A review on preclinical and clinical investigations of this therapeutic concept is provided with evaluation of the issues still to be well deliberated for an effective and safe in-human application

Intraocular Pressure Fluctuation: Is It Important?

Elevated intraocular pressure (IOP) is a major risk factor for the development and progression of glaucoma. Previous prospective, randomized, long-term studies have demonstrated the strength of IOP reduction in slowing the progression of disease. It is well known that IOP is not a fixed value but fluctuates considerably over time. Although there have been some studies on IOP fluctuation and the progression of glaucoma, whether IOP fluctuation is an independent risk factor for glaucomatous damage and disease progression remains controversial. In this article, we reviewed the definition of IOP fluctuation, and both the evidence and the speculation for and against the effect of IOP fluctuation on glaucoma progression. Although conclusions seem to vary from study to study, we considered that different studies examined different groups of patients, at different stages of disease, and at different IOP levels. Our conclusion is that these apparently disparate results are not conflicting, but rather can be viewed as complementary. In clinical care, we recommend the consideration of IOP "modulation" rather than just IOP "reduction" when glaucoma patients are treated. Quality-based IOP control may be more effective than quantity-based IOP reduction to prevent or retard disease progression

A large multi-ethnic genome-wide association study identifies novel genetic loci for intraocular pressure.

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma, a leading cause of blindness. IOP heritability has been estimated to up to 67%, and to date only 11 IOP loci have been reported, accounting for 1.5% of IOP variability. Here, we conduct a genome-wide association study of IOP in 69,756 untreated individuals of European, Latino, Asian, and African ancestry. Multiple longitudinal IOP measurements were collected through electronic health records and, in total, 356,987 measurements were included. We identify 47 genome-wide significant IOP-associated loci (P < 5 × 10-8); of the 40 novel loci, 14 replicate at Bonferroni significance in an external genome-wide association study analysis of 37,930 individuals of European and Asian descent. We further examine their effect on the risk of glaucoma within our discovery sample. Using longitudinal IOP measurements from electronic health records improves our power to identify new variants, which together explain 3.7% of IOP variation

Feeling the pressure: a cross-sectional study exploring feasibility of a healthcare Pop-Up for intraocular pressure measurements in shopping centres in England

OBJECTIVES: To test the hypothesis that a shopping centre Pop-Up health check combining an intraocular pressure (IOP) check with a general health check (blood pressure (BP)) is more readily accepted by the general public than an IOP check only. We investigate public awareness of IOP compared with BP and the feasibility of measuring IOP in large numbers in a Pop-Up. DESIGN: A cross-sectional study using a tailor-made healthcare Pop-Up. SETTING: The 'Feeling the Pressure' Pop-Up was sited in eight regionally-different shopping centres in England. PARTICIPANTS: Adult members of the public in shopping centres. METHODS: On one day we measured IOP only and on another measured BP and IOP. IOP was measured by Icare IC100 tonometer (Helsinki, Finland). Potential participants were asked about their awareness of IOP and BP and when they last visited their optometrist. RESULTS: More people attended the combined BP + IOP days (461; 60%; 95% CI 56% to 64%) than IOP-only days (307; 40%, 95% CI 37% to 43%) over 16 days of testing. We recorded IOP in 652 participants (median (IQR) age and IOP of 54 (42 to 68) years and 13 (11 to 15) mm Hg, respectively). Fewer people reported awareness about IOP (19%, 95% CI 16% to 23%) compared with BP (71%, 95% CI 66% to 75%). Of 768 participants, 60 (8%) reported no previous optometric eye examination and 185 (24%) reported >2 years since their most recent examination. CONCLUSIONS: Measuring IOP in large numbers of the public via a shopping centre Pop-Up is feasible. Public engagement was greater when a BP check was offered alongside an IOP check, suggesting unfamiliar health checks can be promoted by aligning them with a more familiar check. Our findings hint at strategies for public health schemes that engage the public with their eye health

Cataract surgery in eyes with filtered primary angle closure glaucoma.

PurposeTo evaluate the effect of cataract surgery on intraocular pressure (IOP) in filtered eyes with primary angle closure glaucoma (PACG).MethodsIn this prospective interventional case series, 37 previously filtered eyes from 37 PACG patients with mean age of 62.1±10.4 years were consecutively enrolled. All patients had visually significant cataracts and phacoemulsification was performed at least 12 months after trabeculectomy. Visual acuity, IOP and the number of glaucoma medications were recorded preoperatively, and 1, 3, 6 and 12 months after surgery. Anterior chamber (AC) depth was measured preoperatively and 3 months after cataract surgery with A-scan ultrasonography. The main outcome measure was IOP at 12 months.ResultsIOP was decreased significantly from 18.16±5.91 mmHg at baseline to 15.37±2.90 mmHg at final follow-up (P<0.01). The mean number of glaucoma medications was significantly decreased from 1.81±0.24 to 0.86±1.00 (P=0.001) at 1 year postoperatively. At final follow up, 36 (97.2%) eyes and 32 (86.4%) eyes had IOP≤21 and IOP≤18 mmHg, respectively; 14 (37.8%) eyes and 9 (24.3%) eyes had IOP≤21 and IOP≤18 mmHg without medications, respectively. The magnitude of IOP reduction was correlated with higher preoperative IOP (r=0.85, P<0.001), shallower preoperative AC depth (r=-0.38, P=0.01) and greater changes in AC depth (r=-0.39, P=0.01).ConclusionCataract surgery reduces IOP and the number of glaucoma medications in previously filtered PACG eyes. This reduction seems to be greater in patients with higher preoperative IOP and shallower anterior chambers

IOP modeling study

A detailed model of the IOP was developed and used to evaluate IOP performance and its effect of flight software performance. A redesign of FIOMCNTL, the MSC control program, is recommended

Rapid and Accurate Pressure Sensing Device for Direct Measurement of Intraocular Pressure.

PurposeIntraocular pressure (IOP) is the primary modifiable risk factor for glaucoma. Current devices measure IOP via the dynamic response of the healthy cornea and do not provide the accurate IOP measurements for patients with altered corneal biomechanics. We seek to develop and test an accurate needle-based IOP measurement device that is not cornea dependent.MethodsOur device combines a high-resolution pressure microsensor with 30- and 33-gauge Luer lock needles to provide IOP measurements via a microcontroller and USB interface to a computer. The device was calibrated in a membrane chamber and then tested and validated in the anterior chamber and post-vitrectomy vitreous chamber of rabbit eyes. The results were compared to Tonopen readings across a pressure range of 0 to 100 mm Hg, imposed in increments of 10 mm Hg.ResultsBoth the needle based sensor device and the Tonopen demonstrated a linear relationship with changes in imposed pressure. The Tonopen was found to consistently underestimate the IOP both in the anterior and vitreous chambers. The Tonopen exhibited a significantly greater error than our needle-based sensor device. With increased pressure (>30 mm Hg), the error of the Tonopen increased, whereas the error of our device did not. The 30-gauge needle produces an insignificant improvement in accuracy over the 33-gauge needle.ConclusionsA needle-based sensor device enables accurate IOP measurements over a broad range of induced IOP.Translational relevanceDirect measurement of IOP in the anterior chamber circumvents the influence of corneal parameters on IOP measurement

Intraocular pressure in a cohort of healthy Eastern European schoolchildren: variations in method and corneal thickness

BACKGROUND: Intraocular pressure (IOP) in the developing eye of a child is not always easy to measure and there is no technique that is known to be the most accurate for the young eye. Measurements are needed on many cohorts of children with different tonometers to determine how the values correlate between instruments, whether corneal parameters affect readings and whether correlations between age and IOP values can be discerned. The aim of this study was to undertake a comparative analysis of three different tonometers on a group of healthy children to see whether differences exist and whether these may be related to central corneal thickness and/or radius of curvature. In addition, the study adds to the relatively small body of literature on IOP in the growing eye which will collectively allow trends to be identified and ultimately norms to be established. METHODS: IOP was measured on 115 eyes in a group of Polish children, aged between 5-17 years (mean±standard deviation [SD] 11.3±3.0 years) using three different tonometers: non-contact (NCT), the ICare and Goldmann applanation (GAT). Readings obtained were compared between instruments and with central corneal thickness and radius of curvature. RESULTS: The ICare tonometer provided statistically higher IOP values (16.9±3.4 mmHg) than the GAT (14.7±2.9 mmHg) regardless of corneal thickness and whether or not a correction factor was applied. A correlation was found between central corneal thickness (CCT) and IOP values obtained with all three tonometers but only the IOP values detected with the ICare tonometer showed a statistically significant correlation with radius of curvature (p<0.004). No correlations with age or gender were found for IOP values measured with any of the instruments. CONCLUSIONS: IOP measurements on children vary significantly between instruments and correlations are affected by the corneal thickness. Further studies on children are needed to determine which instrument is most appropriate and to derive a normative IOP scale for the growing eye

Outcomes of ab interno trabeculectomy with the trabectome by degree of angle opening.

AimTo analyse ab interno trabeculectomy (AIT) with the trabectome and combined phacoemulsification with AIT (phaco-AIT) by Shaffer angle grade (SG).MethodsProspective study of AIT and phaco-AIT with narrow angles of SG≤2 versus open angles ≥3. Outcomes included intraocular pressure (IOP), medications, complications, secondary surgery and success (IOP &lt;21 mm Hg and &gt;20% reduction without further surgery). Exclusion criteria were missing preoperative data and &lt;1 year follow-up.ResultsOf 671 included cases, at 1 year AIT SG≤2 (n=43) had an IOP reduction of 42% from 27.3±7.4 to 15.7±3.0 mm Hg (p&lt;0.01) versus AIT SG≥3 (n=271) with an IOP reduction of 37% from 26.1±7.8 to 16.4±3.9 mm Hg (p&lt;0.01). In phaco-AIT with SG≤2 (n=48), IOP was reduced 24% from 20.7±7.0 to 15.7±3.6 mm Hg (p&lt;0.01) versus phaco-AIT with SG≥3 (n=309) with an IOP reduction of 25% from 22.6±6.4 to 17.0±3.4 mm Hg (p&lt;0.01). There was no difference between SG≤2 and SG≥3 in reduction of IOP or medications, complications, secondary surgery and success rates (p&gt;0.05).ConclusionsSG≤2 is not associated with worse outcomes in AIT or phaco-AIT