Membrane Lens Research Articles

Biologicals and Biomaterials for Corneal Regeneration and Vision Restoration in Limbal Stem Cell Deficiency.

The mammalian cornea is decorated with stem cells bestowed with the life-long task of renewing the epithelium, provided they remain healthy, functional, and in sufficient numbers. If not, a debilitating disease known as limbal stem cell deficiency (LSCD) can develop causing blindness. Decades after the first stem cell (SC) therapy is devised to treat this condition, patients continue to suffer unacceptable failures. During this time, improvements to therapeutics have included identifying better markers to isolate robust SC populations and nurturing them on crudely modified biological or biomaterial scaffolds including human amniotic membrane, fibrin, and contact lenses, prior to their delivery. Researchers are now gathering information about the biomolecular and biomechanical properties of the corneal SC niche to decipher what biological and/or synthetic materials can be incorporated into these carriers. Advances in biomedical engineering including electrospinning and 3D bioprinting with surface functionalization and micropatterning, and self-assembly models, have generated a wealth of biocompatible, biodegradable, integrating scaffolds to choose from, some of which are being tested for their SC delivery capacity in the hope of improving clinical outcomes for patients with LSCD.

Interaction of βL- and γ-Crystallin with Phospholipid Membrane Using Atomic Force Microscopy.

Highly concentrated lens proteins, mostly β- and γ-crystallin, are responsible for maintaining the structure and refractivity of the eye lens. However, with aging and cataract formation, β- and γ-crystallin are associated with the lens membrane or other lens proteins forming high-molecular-weight proteins, which further associate with the lens membrane, leading to light scattering and cataract development. The mechanism by which β- and γ-crystallin are associated with the lens membrane is unknown. This work aims to study the interaction of β- and γ-crystallin with the phospholipid membrane with and without cholesterol (Chol) with the overall goal of understanding the role of phospholipid and Chol in β- and γ-crystallin association with the membrane. Small unilamellar vesicles made of Chol/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (Chol/POPC) membranes with varying Chol content were prepared using the rapid solvent exchange method followed by probe tip sonication and then dispensed on freshly cleaved mica disk to prepare a supported lipid membrane. The βL- and γ-crystallin from the cortex of the bovine lens was used to investigate the time-dependent association of βL- and γ-crystallin with the membrane by obtaining the topographical images using atomic force microscopy. Our study showed that βL-crystallin formed semi-transmembrane defects, whereas γ-crystallin formed transmembrane defects on the phospholipid membrane. The size of semi-transmembrane defects increases significantly with incubation time when βL-crystallin interacts with the membrane. In contrast, no significant increase in transmembrane defect size was observed in the case of γ-crystallin. Our result shows that Chol inhibits the formation of membrane defects when βL- and γ-crystallin interact with the Chol/POPC membrane, where the degree of inhibition depends upon the amount of Chol content in the membrane. At a Chol/POPC mixing ratio of 0.3, membrane defects were observed when both βL- and γ-crystallin interacted with the membrane. However, at a Chol/POPC mixing ratio of 1, no association of γ-crystallin with the membrane was observed, which resulted in a defect-free membrane, and the severity of the membrane defect was decreased when βL-crystallin interacted with the membrane. The semi-transmembrane or transmembrane defects formed by the interaction of βL- and γ-crystallin on phospholipid membrane might be responsible for light scattering and cataract formation. However, Chol suppressed the formation of such defects in the membrane, likely maintaining lens membrane homeostasis and protecting against cataract formation.

Higher order wavefront correction and axial scanning in a single fast and compact piezo-driven adaptive lens.

We present a compact adaptive glass membrane lens for higher order wavefront correction and axial scanning, driven by integrated segmented piezoelectric actuators. The membrane can be deformed in a combination of rotational symmetry providing focus control of up to ± 6 m-1 and spherical aberration correction of up to 5 wavelengths and different discrete symmetries to correct higher order aberrations such as astigmatism, coma and trefoil by up to 10 wavelengths. Our design provides a large clear aperture of 12 mm at an outer diameter of the actuator of 18 mm, a thickness of 2 mm and a response time of less than 2 ms.

Reliability of tunable lenses: feedback sensors and the influence of temperature, orientation, and vibrations.

We compare different aspects of the robustness to environmental conditions of two different types of piezo-actuated fluid-membrane lenses: a silicone membrane lens, where the piezo actuator indirectly deforms the flexible membrane through fluid displacement, and a glass membrane lens, where the piezo actuator directly deforms the stiff membrane. While both lenses operated reliably over the temperature range of 0°-75°C, there was a significant effect on their actuation characteristics, which can be well described through a simple model. The silicone lens in particular showed a variation in focal power of up to 0.1m-1 ∘C-1. We demonstrated that integrated pressure and temperature sensors can provide feedback for focal power, however, limited by the response time of the elastomers in the lenses, with polyurethane in the support structures of the glass membrane lens being more critical than the silicone. Studying the mechanical effects, the silicone membrane lens showed a gravity-induced coma and tilt, and a reduced imaging quality with the Strehl ratio decreasing from 0.89 to 0.31 at a vibration frequency of 100Hz and an acceleration of 3g. The glass membrane lens was unaffected by gravity, and the Strehl ratio decreased from 0.92 to 0.73 at a vibration of 100Hz, 3g. Overall, the stiffer glass membrane lens is more robust against environmental influences.

Diffractive Alvarez-Lohmann lenses for correcting aberrations of tunable membrane lenses

Focus-tunable lenses, e.g., liquid filled membrane lenses (MLs), have found increasingly widespread application in optical systems. If a large refractive power range is to be used, the correction of chromatic aberrations is particularly challenging: a group containing a single ML cannot be corrected over the whole refractive power range. In analogy to hybrid achromats for lenses with constant focal lengths, we present the combination of an ML and a diffractive Alvarez-Lohmann-lens (ALL) for the compensation of axial color over a large refractive power range. In contrast to the combination of multiple MLs, this does not increase the axial length of the system significantly. At the same time, the flexible adaption of the phase function of the diffractive ALL can reduce spherical aberration over the whole focal range. Design examples with ray-tracing and wave-optical simulations demonstrate the performance of the resulting hybrid tunable element. Experimental data from fabricated sample lenses provide a proof of principle.

Smartphone-based fluorescent sensing platforms for point-of-care ocular lactoferrin detection

Lactoferrin is a critical glycoprotein that accounts for the major component in tear protein composition. Tear lactoferrin has been indicated as a potential biomarker in ocular health screening, such as dry eye disease diagnosis. Fluorescent biosensors are a desirable alternative to current diagnostic methods, due to their high selectivity and sensitivity, and rapid and cost-effective detection technologies at point-of-care (POC) platforms. Herein, fluorescent lactoferrin sensing is examined and applied on nitrocellulose membrane, capillary tube, and contact lens platforms in cooperation with a developed smartphone software for data collection and analysis. Fluorescent sensors based on trivalent terbium (TbCl3) are integrated into different platforms, including nitrocellulose membranes, capillary tubes, and contact lenses, and tested in artificial tear fluid. A bespoke 3D printed readout device integrated with a smartphone camera was employed for image acquisition and readout. The detection range of the lactoferrin sensors could be varied from 0 to 5 mg mL−1 with a strong linear relation and yielded a limit of detection (LOD) of 0.57 mg mL−1 for lateral flow sensing, 0.12 mg mL−1 for capillary tube sensing, and 0.44 mg mL−1 for contact lens sensing. The contact lens sensor obtained the highest linear regression, while the capillary tube sensor achieved a lowest LOD. This work could pave the way towards accessible lactoferrin monitoring at POC and could induce hospitalization at the UK national health service (NHS) for future clinical trials and examinations.

Tunable doublets: piezoelectric glass membrane lenses with an achromatic and spherical aberration control.

We present two versions of tunable achromatic doublets based on each two piezoelectrically actuated glass membranes that create the surface of fluid volumes with different dispersions: a straightforward back-to-back and a more intricate stack of the fluid volumes. In both cases, we can control the chromatic focal shift and focal power independently by a suitable combination of actuation voltages on both active membranes. The doublets have a large aperture of 12 mm at an outer diameter of the actuator of 18 mm, an overall thickness of 3 mm and a short response time of around 0.5 ms and, in addition, provide spherical aberration correction. The two designs have an achromatic focal power range of ±2.2 m-1 and ±3.2 m-1 or, for the purpose of actively correcting chromatic errors, a chromatic focal shift at vanishing combined focal power of up to ±0.08 m-1 and ±0.12 m-1.

Lens Nucleation and Droplet Budding in a Membrane Model for Lipid Droplet Biogenesis.

Lipid droplet biogenesis comprises the emergence of cytosolic lipid droplets with a typical diameter 0.1-5 μm via synthesis of fat in the endoplasmatic reticulum, the formation of membrane-embedded lenses, and the eventual budding of lenses into solution as droplets. Lipid droplets in cells are increasingly being viewed as highly dynamic organelles with multiple functions in cell physiology. However, the mechanism of droplet formation in cells remains poorly understood, partly because their formation involves the rapid transformation of transient lipid structures that are difficult to capture. Thus, the development of controlled experimental systems that model lipid biogenesis is highly relevant for an enhanced mechanistic understanding. Here we prepare and characterize triolein (TO) lenses in a multilamellar spin-coated phosphatidylcholine (POPC) film and determine the lens nucleation threshold to 0.25-0.5% TO. The TO lens shapes are characterized by atomic force microscopy (AFM) including their mean cap angle ⟨α⟩ = 27.3° and base radius ⟨a⟩ = 152.7 nm. A cross-correlation analysis of corresponding AFM and fluorescence images confirms that TO is localized to lenses. Hydration of the lipid/lens film induces the gel to fluid membrane phase transition and makes the lenses more mobile. The budding of free droplets into solution from membrane lenses is detected by observing a change in motion from confined wiggling to ballistic motion of droplets in solution. The results confirm that droplet budding can occur spontaneously without being facilitated by proteins. The developed model system provides a controlled platform for testing mechanisms of lipid droplet biogenesis in vitro and addressing questions related to lens formation and droplet budding by quantitative image analysis.

Neurotrophic Keratopathy in the United States: An Intelligent Research in Sight Registry Analysis

To describe the characteristics of neurotrophic keratopathy (NK) in the United States. Retrospective database study. Thirty-one thousand nine hundred fifteen eyes of 27 483 patients with a diagnosis of NK. Retrospective analysis of visits associated with a diagnosis of NK between 2013 and 2018 using the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry. Demographic information, prevalence, visual acuity (VA), concomitant diagnosis and procedure codes, and risk factors impacting VA most closely after NK onset date. Mean ± standard deviation (SD) age at initial diagnosis of NK was 68.0 ± 16.0 years, and 58.91% of patients were women (P < 0.0001). Presentation was unilateral in 58.14%, bilateral in 16.13%, and unspecified in 25.73%. Average 6-year prevalence of NK in the IRIS Registry was 21.34 cases per 100 000 patients. Mean ± SD VA was 0.60 ± 0.79 logMAR before diagnosis and 0.88 ± 0.94 logMAR after diagnosis (P < 0.0001). Most common concomitant diagnoses included herpetic keratitis (33.70%), diabetes (31.59%), and corneal dystrophy (14.28%). Common procedures for NK management included the use of amniotic membrane (29.90%), punctal plugs (29.65%), and bandage contact lenses (22.67%). Age, male sex, Black race, Hispanic or Latino ethnicity, unilateral involvement, concomitant diagnoses of diabetes, corneal transplantation, and herpetic keratitis were associated significantly with worse VA. Based on the IRIS Registry, the prevalence of NK is 21.34 cases per 100 000 patients. Visual acuity was significantly worse after NK diagnosis compared with other time points. Neurotrophic keratopathy was associated most commonly with herpetic keratitis and diabetes. Worse VA in patients with NK was associated with several demographic characteristics, history of diabetes, corneal transplantation, and herpetic keratitis.

Sutureless dehydrated amniotic membrane for persistent epithelial defects.

To report outcomes of a sutureless dehydrated amniotic membrane for persistent epithelial defects (PED). This retrospective study included consecutive patients with a PED (⩾14 days) treated with a sutureless dehydrated amniotic membrane and bandage contact lens (BCL). Included were patients with an epithelial defect that did not respond to treatment with a BCL. Excluded were patients with a follow-up time of less than 3 months. Nine eyes of eight patients with a mean age of 54.6 ± 10.9 years (range 38-73 years) were included in this study. The main etiology of the PED was limbal stem cell deficiency (n = 5/9) due to Stevens-Johnson Syndrome (n = 2/5), glaucoma procedures (n = 1/5), graft-versus-host disease (n = 1/5) and severe allergic reaction (n = 1/5). Additional etiologies included neurotrophic cornea (n = 2/9), post keratoplasty and severe dry eye disease (n = 2/9). Time from PED presentation to amnion treatment was 65.9 ± 60.6 days (range 15-189 days) with the area of the PED being 11.0 ± 12.2 mm2 (range 1.0-36.0 mm2). The amnion was absorbed within 2 weeks in 100% of the cases. Following insertion of the amnion, resolution of the PED was achieved in 8/9 eyes (89%) without the need for additional interventions within 17.8 ± 9.6 days (range 7-35 days). LogMAR BCVA improved from 0.94 ± 0.88 to 0.37 ± 0.25 (p = 0.036) with no complications or recurrences recorded. Sutureless dehydrated amniotic membrane achieved resolution of PEDs secondary to various etiologies in 89% of eyes with a significant improvement in vision demonstrated. Further studies are needed to assess long term safety and effectiveness.

Copolyamide-Imide Membrane with Low CTE and CME for Potential Space Optical Applications.

Polyimide diffractive membrane lens can be used in space optical telescope to reduce the size and mass of an imaging system. However, traditional commercial aromatic polyimide membrane is hard to meet the challenging requirements of dimensional stability and optical homogeneity for optical use. Based on molecular structure design and the optimization of fabrication process, the prepared copolyamide-imide membrane achieved the desired performance of membrane as an optical material. It showed a very low coefficient of thermal expansion (CTE), which is 0.95 ppm/°C over a temperature range of −150–100 °C and relatively low coefficient of moisture expansion (CME), which is only 13.30 ppm/% RH (0~90% RH). For the optical use, the prepared copolyamide-imide membrane (φ200 mm) achieved good thickness uniformity with wave-front error smaller than λ/30 (λ = 632 nm) in RMS (root mean square). Besides, it simultaneously meets the optical, thermal, and mechanical requirements for space telescope use. Copolyamide-imide membranes in this research with good comprehensive performance can be used as large aperture membrane optical system architectures.

Design of zoom systems composed of lenses with variable focal length.

This paper develops a methodology for a design of zoom-systems, which are composed of thin optical components with a variable focal length (e.g., membrane lenses). The proposed procedure allows us to design not only the outer parameters of the system (focal lengths and separation of lenses), but the inner structure of individual components of the system can be calculated as well (radii of curvature, thicknesses, and refractive indices) i.e., the starting values of the mentioned parameters can be calculated and used for the next optimization.

Double curvature membrane lens.

The paper presents a theoretical analysis of properties of a specific liquid membrane lens composed of two axially symmetric membranes of different thicknesses and double curvature. These membranes enclose a space where an optical liquid is filled. Mechanical and optical properties of the lens are then changed by varying the volume of the liquid. The paper presents new formulas for calculation of membrane deflections, radii of curvatures of the membranes, and axial geometry, which offer to minimize the third-order spherical aberration of the lens for an object at infinity. The presented theory is examined on specific examples.

A microfluidically controlled concave\u2013convex membrane lens using an addressing operation system

Electrical control toolkits for microlens arrays are available to some extent, but for applications in environments with strong electromagnetic fields, radiation, or deep water, non-electrical actuation and control strategies are more appropriate. An integrated digital microfluidic zoom actuating unit with a logic addressing unit for a built-in membrane lens array, e.g., a flexible bionic compound eye, is developed and studied in this article. A concave–convex membrane fluidic microvalve, which is the component element of the logic gate, actuator, and microlens, is proposed to replace the traditional solenoid valve. The functions of pressure regulation and decoding can be obtained by incorporating microvalves into fluidic networks according to equivalent circuit designs. The zoom actuating unit contains a pressure regulator to adjust the focal length of lenses with three levels, and the logic addressing unit contains a decoder to choose a typical lens from a hexagonal lens array. The microfluidic chip control system is connected flexibly to the actuating part, a membrane lens array. It is shown from a simulation and experimental demonstration that the designed and fabricated system, which is composed of a whole microfluidic zoom unit, addressing technology, and a microlens array, works well. Because these components are constructed in the same fabrication process and operate with the same work media and driving source, the system can be made highly compatible and lightweight for applications such as human-machine interfaces and soft robots.

Multiphysics simulation of the aspherical deformation of piezo-glass membrane lenses including hysteresis, fabrication and nonlinear effects

In this paper we present and verify the nonlinear simulation of an aspherical adaptive lens based on a piezo-glass sandwich membrane with combined bending and buckling actuation. To predict the full nonlinear piezoelectric behavior, we measured the nonlinear charge coefficient, hysteresis and creep effects of the piezo material and inserted them into the FEM model using a virtual electric field. We further included and discussed the fabrication parameters—glue layers and thermal stress—and their variations. To verify our simulations, we fabricated and measured a set of lenses with different geometries, where we found good agreement and show that their qualitative behavior is also well described by a simple analytical model. We finally discuss the effects of the geometry on the electric response and find, e.g. an increased focal power range from ±4.5 to when changing the aperture from 14 to .

Dependence of the imaging properties of the liquid lens with variable focal length on membrane thickness.

This paper presents the influence of membrane thickness on imaging properties of membrane liquid lenses with variable focal length. Approximate formulas for varying thickness of spherically and parabolically deformed membrane were derived, which allows us to determine their influence on quality of imaging properties of a membrane liquid lens. Furthermore, formulas for wave spherical aberration calculation of a membrane and liquid lens body were derived. It has been shown that the influence of membrane thickness and its changes on wave spherical aberration is negligible from a practical point of view.

Native and synthetic scaffolds for limbal epithelial stem cell transplantation.

The outcome of patients with corneal blindness that receive stem cell grafts to restore eye health and correct vision varies considerably and may be due to the different biological and synthetic scaffolds used to deliver these cells to the ocular surface. This review will highlight the positive attributes and limitations of the myriad of carriers developed for clinical use as well as those that are being trialled in pre-clinical models. The overall focus is on developing a standardized therapy for patients, however due to the multiple causes of corneal blindness, a personal regenerative medicine approach may be the best option.

A 3D scanning laser endoscope architecture utilizing a circular piezoelectric membrane

A piezo-scanning fiber endoscopic device architecture is proposed for 3D imaging or ablation. The endoscopic device consists of a piezoelectric membrane that is placed perpendicular to the optical axis, a fiber optic cable that extends out from and actuated by the piezoelectric membrane, and one or multiple lenses for beam delivery and collection. Unlike its counterparts that utilize piezoelectric cylinders for fiber actuation, the proposed architecture offers quasi-static actuation in the axial direction along with resonant actuation in the lateral directions forming a 3D scanning pattern, allowing adjustment of the focus plane. The actuation of the four-quadrant piezoelectric membrane involves driving of two orthogonal electrodes with AC signals for lateral scanning, while simultaneously driving all electrodes for axial scanning and focus adjustment. We have characterized piezoelectric membranes (5 –15mm diameter) with varying sizes to monitor axial displacement behavior with respect to applied DC voltage. We also demonstrate simultaneous lateral and axial actuation on a resolution target, and observe the change of lateral resolution on a selected plane through performing 1D cross-sectional images, as an indicator of focal shift through axial actuation. Based on experimental results, we identify the optical and geometrical parameters for optimal 3D imaging of tissue samples. Our findings reveal that a simple piezoelectric membrane, having comparable dimensions and drive voltage requirement with off-the-shelf MEMS scanner chips, offers tissue epithelial imaging with sub-cellular resolution.

Evaluating Structural Progression of Retinitis Pigmentosa After Cataract Surgery

To determine whether cataract surgery accelerates disease progression in retinitis pigmentosa (RP). Retrospective cohort study. Seventy eyes of 40 patients with RP were categorized as having had phacoemulsification with intraocular lens implantation vs no cataract surgery at a single tertiary-level institution. Spectral-domain optical coherence tomography (SDOCT) was used to measure the ellipsoid zone (EZ) width, which has been demonstrated to be a reliable marker of RP severity, at baseline and throughout follow-up (median 768days). RP progression was calculated as the loss of EZ width over time for all patients. Additional postoperative data were collected for the cataract surgery group, including preoperative and postoperative best-corrected visual acuity, incidence of macular edema, posterior capsular opacification, epiretinal membrane, and intraocular lens subluxation. Multivariable analysis including age, baseline EZ width, mode of inheritance, and cataract surgery status showed that there was no significant difference in RP progression between the cataract surgery and control groups (P= .23). Mode of inheritance was associated with RP progression, with autosomal recessive RP progressing at 148μm/year and autosomal dominant RP progressing at 91μm/year (P= .003). Visual acuity improved in almost all eyes that underwent surgery (17/19, 89%) and remained stable in remaining eyes (2/19, 11%). There was a high incidence of postsurgical posterior capsular opacification (18/19, 95%). There were no serious complications, such as lens subluxation or endophthalmitis. Our findings suggest that cataract surgery is a safe and effective means of improving visual acuity in RP patients and that it does not seem to be associated with faster disease progression as measured using SDOCT.

Gravity-immune liquid-filled tunable lens with reduced spherical aberration.

The performance of uniform-thickness membrane lenses is severely compromised due to the inherent trade-off between spherical aberration and the sensitivity to gravity effects. This problem can be eliminated by engineering the membrane thickness profile such that a membrane stiff enough to withstand gravity-induced deformations can be shaped into a perfect optical surface under uniform pressure load. We present here a membrane-based liquid-tunable aspherical lens capable of diffraction-limited performance at nominal focal length, with two orders-of-magnitude smaller wavefront error compared to conventional tunable lenses, regardless of the lens orientation, by use of a non-uniform thickness profile of the flexible membrane. The lens has an aperture size of 3mm, with a nominal focal length of 8mm and a theoretical diffraction-limited tuning range between 7.2 and 8.8mm. Between 6 and 12mm, the cutoff frequency remains above 50% of the diffraction limit, demonstrating a drastic reduction in spherical aberration compared to conventional liquid-tunable lenses.