Effect of compound treatments on mouse lens viscoelasticity.

Previous studies have shown that pharmaceutical agents such as lipoic acid have the ability to soften the lens, presenting a promising avenue for treating presbyopia. One obstacle encountered in the preclinical stage of such agents is the need for precise measurements of lens elasticity in experimental models. This study aimed to evaluate the effects of 25-hydroxycholesterol, lipoic acid, and obeticholic acid on the viscoelastic properties of mouse lenses using a custom-built elastometer system. Data were acquired on lenses from C57BL/6J female mice from two age groups: young (age: 8-10 weeks) and old (age: 32-43 weeks). OD lenses were used as the control and OS lenses were treated. Control lenses were immersed in Dulbecco's Modified Eagle Medium (DMEM) and treatment lenses were immersed in a compound solution containing 25-hydroxycholesterol (5 young and 5 old), lipoic acid at 2.35 mM (5 young and 5 old), lipoic acid at 0.66 mM (5 old), or obeticholic acid (5 old) at 37 °C for 18 h. After treatment, the mouse lenses were placed in a DMEM-filled chamber within a custom-built elastometer system that recorded the load and lens shape as the lens was compressed by 600 µm at a speed of 50 µm/s. The load was continuously recorded during compression and during stress-relaxation. The compression phase was fit with a linear function to quantify lens stiffness. The stress-relaxation phase was fit with a 3-term exponential relaxation model providing relaxation time constants (t1, t2, t3), and equilibrium load. The lens stiffness, time constants and equilibrium load were compared for the control and treated groups. Results revealed an increase in stiffness with age for the control group (young: 1.16 ± 0.11 g/mm, old: 1.29 ± 0.14 g/mm) and relaxation time constants decreased with age (young: t1 = 221.9 ± 29.0 s, t2 = 24.7 ± 3.8 s, t3 = 3.12 ± 0.87 s, old: t1 = 183.0 ± 22.0 s, t2 = 20.6 ± 2.6 s and t3 = 2.24 ± 0.43 s). Among the compounds tested, only 25-hydroxycholesterol produced statistically significant changes in the lens stiffness, relaxation time constants, and equilibrium load. In conclusion, older mouse lenses are stiffer and less viscous than young mouse lenses. Notably, no significant change in lens stiffness was observed following treatment with lipoic acid, contrary to previous findings.

Temperature affects the biomechanical response of in vitro non-human primate lenses during lens stretching.

PURPOSE: To determine the effect of temperature on the accommodative response of non-human primate crystalline lenses during simulated accommodation. METHODS: Eight lenses from 7 cynomolgus monkeys (Macaca fascicularis, ages: 4.5-7.3 years; post-mortem time: 17.0 ± 16.4 h) were mounted in a lens stretcher. Stretching experiments were performed on each lens at 24 °C (room temperature), then the tissue was warmed to 35 °C (intraocular temperature) and the stretching experiments were repeated. The lens diameter, thickness, anterior and posterior surface radii of curvature, optical power, and the stretching force (load) were measured at each stretch position and the linear optomechanical relationships were quantified: load-lens diameter, load-thickness, power-load, load-anterior radius, and load-posterior radius. The rate of change for each parameter was quantified by performing a linear regression. The slopes of the linear regressions were compared at the two temperatures using a paired sample t-test. RESULTS: The average changes in the lens with stretching at 24 °C and 35 °C were: 3.07 ± 0.17 and 2.58 ± 0.15 for load-lens diameter (g/mm), -2.38 ± 0.20 and -2.00 ± 0.32 for load-thickness (g/mm), -13.35 ± 1.21 and -13.75 ± 1.26 for power-load (D/g), 0.41 ± 0.10 and 0.34 ± 0.05 for load-anterior radius of curvature (g/mm), and 1.35 ± 0.24 and 1.31 ± 0.35 for load-posterior radius of curvature (g/mm), respectively. The changes in load-diameter and load-thickness with lens stretching were significantly different for the two temperatures. CONCLUSIONS: Temperature influences the change in lens shape observed during simulated accommodation in non-human primate lenses. These results suggest that lens stretching experiments and other optomechanical measurement techniques on ex vivo crystalline lenses be conducted at 35 °C and that the temperature of the tissue sample be documented and maintained constant to ensure repeatability.

Cellular and molecular assessment of rose bengal photodynamic antimicrobial therapy on keratocytes, corneal endothelium and limbal stem cell niche.

Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT) is a novel potential treatment for progressive infectious keratitis. The principle behind this therapy is using Rose Bengal as a photosensitizer that can be activated by green light and results in the production of oxygen free radicals which in turn eradicate the microorganism. Given RB-PDAT's mechanism of action and the potential cytotoxic effects, concerns regarding the safety of this technique have arisen. The purpose of this study was to evaluate the effect of RB-PDAT on keratocytes, while focusing on the safety profile that the photo-chemical reaction has on the limbal stem cell (LSC) niche and endothelial cell layer of the treated cornea. To perform RB-PDAT, Rose Bengal solution (0.1% RB in BSS) was applied to the right cornea of rabbits for 30 min and then irradiated by a custom-made green LED light source (525 nm, 6 mW/cm2) for 15 min (5.4 J/cm2). Three rabbits were sacrificed and enucleated after 24 h for evaluation. TUNEL assay and immunohistochemistry for endothelium and limbal stem cell viability were performed on whole mounts and frozen sections in treated and control eyes. LSC of both eyes were isolated and cultured to perform MTT viability and proliferation, and scratch wound healing assays under time-lapse microscopy. Interestingly, while Rose Bengal dye penetration was superficial, yet associated cellular apoptosis was evidenced in up to 1/3 of the stromal thickness on frozen sections. TUNEL assay on whole mounts showed no endothelial cell death following treatment. Immunohistochemistry on frozen sections of LSC displayed no structural difference between treated and non-treated eyes. There was no difference in LSC proliferation rates and scratch wound healing assay demonstrated adequate cell migration from treated and non-treated eyes. The current study suggests that even though penetration of the RB dye has been shown to be limited, oxidative stress produced by RB-PDAT can reach deeper into the corneal stroma. Nevertheless, our results show that performing RB-PDAT is safe on the corneal endothelium and has no effect on LSC viability or function.

Are ultrasound-guided ophthalmic blocks injurious to the eye? A comparative rabbit model study of two ultrasound devices evaluating intraorbital thermal and structural changes.

BACKGROUND: Since Atkinson's original description of retrobulbar block in 1936, needle-based anesthetic techniques have become integral to ophthalmic anesthesia. These techniques are unfortunately associated with rare, grave complications such as globe perforation. Ultrasound has gained widespread acceptance for peripheral nerve blockade, but its translation to ocular anesthesia has been hampered because sonic energy, in the guise of thermal or biomechanical insult, is potentially injurious to vulnerable eye tissue. The US Food and Drug Administration (FDA) has defined guidelines for safe use of ultrasound for ophthalmic examination, but most ultrasound devices used by anesthesiologists are not FDA-approved for ocular application because they generate excessive energy. Regulating agencies state that ultrasound examinations can be safely undertaken as long as tissue temperatures do not increase >1.5°C above physiological levels. METHODS: Using a rabbit model, we investigated the thermal and mechanical ocular effects after prolonged ultrasonic exposure to single orbital- and nonorbital-rated devices. In a dual-phase study, aimed at detecting ocular injury, the eyes of 8 rabbits were exposed to continuous 10-minute ultrasound examinations from 2 devices: (1) the Sonosite Micromaxx (nonorbital rated) and (2) the Sonomed VuMax (orbital rated) machines. In phase I, temperatures were continuously monitored via thermocouples implanted within specific eye structures (n = 4). In phase II the eyes were subjected to ultrasonic exposure without surgical intervention (n = 4). All eyes underwent light microscopy examinations, followed at different intervals by histology evaluations conducted by an ophthalmic pathologist. RESULTS: Temperature changes were monitored in the eyes of 4 rabbits. The nonorbital-rated transducer produced increases in ocular tissue temperature that surpassed the safe limit (increases >1.5°C) in the lens of 3 rabbits (at 5.0, 5.5, and 1.5 minutes) and cornea of 2 rabbits (both at 1.5 minutes). A secondary analysis of temporal temperature differences between the orbital-rated and nonorbital transducers revealed statistically significant differences (Bonferroni-adjusted P < 0.05) in the cornea at 3.5 minutes, the lens at 2.5 minutes, and the vitreous at 4.0 minutes. Light microscopy and histology failed to elicit ocular injury in either group. CONCLUSIONS: The nonorbital-rated ultrasound machine (Sonosite Micromaxx) increases the ocular tissue temperature. A larger study is needed to establish safety. Until then, ophthalmic ultrasound-guided blocks should only be performed with ocular-rated devices.

A portable, contact animal fundus imaging system based on Rol's GRIN lenses.

OBJECTIVE: To demonstrate a cost-effective, portable, and simple-to-use fundus imaging system for laboratory animals. ANIMALS STUDIED: Albino rats, pigmented mice, albino guinea pigs, and New Zealand white rabbits. PROCEDURE: A contact fundus imaging system was designed and constructed using standard optical and mechanical components: a digital camera, an otoscope, a fiber optic light source, and standard optical lenses and mounts. Digital fundus video and photography of two albino rats, two pigmented mice, two New Zealand white rabbits, and two albino guinea pigs were obtained. For all animals examined, pupils were dilated and local anesthetic was administered. RESULTS: Digital images of the fundus were obtained in all animals. Contrast of retinal vasculature and overall image quality varied from one species to another, as the axial length, ocular optics, and retinal reflectance varied significantly across species. Light intensity and focus were optimized via the light source and lens focusing mount to produce high-quality images for each animal. CONCLUSIONS: The portable, cost-effective contact fundus imaging system was easy to use for fundus examination of laboratory animals.

Glaucoma Cascade Screening in a High Risk Afro-Caribbean Haitian Population: A Pilot Study.

PRCIS: Glaucoma cascade screening in first-degree relatives (FDRs) of young Haitian glaucoma patients had high yield for diagnosing manifest and suspected glaucoma in 30.8% of those screened despite modest participation. PURPOSE: To evaluate the outcomes of glaucoma cascade screening in FDRs (parents, siblings, and offspring) of Haitian juvenile open-angle glaucoma (JOAG) patients. PATIENTS AND METHODS: Consecutive index patients (Haitians with JOAG) were identified, and the number/type of FDRs residing in South Florida were recorded. These FDRs were invited for free glaucoma screening, which included a comprehensive ophthalmic exam, gonioscopy, automated visual field testing and optical coherence tomographic analysis of the retinal nerve fiber layers. FDR characteristics and clinical findings from screening are reported. RESULTS: A total of 77 FDRs were invited, 26 (33.8%) agreed to undergo screening (18 females, 9 males), which revealed 2 (7.7%) with manifest glaucoma (mean age 77.5 y; one of whom was previously unaware of his glaucoma diagnosis), 6 (23.1%) with suspected glaucoma (mean age 29.8±18.3 y), and 18 (69.2%) without manifest or suspected glaucoma (mean age 37.2±21.8 y). Siblings of index patients were least likely to participate in cascade glaucoma screening when compared with index patients' parents or offspring. FDR eyes with manifest glaucoma had significantly worse best-corrected visual acuities, higher intraocular pressures, thinner central corneal thicknesses, and thinner circumferential papillary retinal nerve fiber layer thicknesses than those without glaucoma. CONCLUSION: Glaucoma cascade screening of Haitian JOAG patients' FDRs revealed that 30.8% had suspected or manifest glaucoma. Future efforts centered on provider-initiated recruitment and improving public glaucoma awareness and education may increase screening participation.

Primate lens capsule elasticity assessed using Atomic Force Microscopy.

The purpose of this project is to measure the elasticity of the human and non-human primate lens capsule at the microscopic scale using Atomic Force Microscopy (AFM). Elasticity measurements were performed using AFM on the excised anterior lens capsule from 9 cynomolgus monkey (5.9-8.0 years), 8 hamadryas baboon (2.8-10.1 years), and 18 human lenses (33-79 years). Anterior capsule specimens were obtained by performing a 5 mm continuous curvilinear capsulorhexis and collecting the resulting disk of capsular tissue. To remove the lens epithelial cells the specimen was soaked in 0.1% trypsin and 0.02% EDTA for 5 min, washed, and placed on a Petri dish and immersed in DMEM. Elasticity measurements of the capsule were performed with a laboratory-built AFM system custom designed for force measurements of ophthalmic tissues. The capsular specimens were probed with an AFM cantilever tip to produce force-indentation curves for each specimen. Young's modulus was calculated from the force-indentation curves using the model of Sneddon for a conical indenter. Young's modulus of elasticity was 20.1-131 kPa for the human lens capsule, 9.19-117 kPa for the cynomolgus lens capsule, and 13.1-62.4 kPa for the baboon lens capsule. Young's modulus increased significantly with age in humans (p = 0.03). The age range of the monkey and baboon samples was not sufficient to justify an analysis of age dependence. The capsule elasticity of young humans (<45 years) was not statistically different from that of the monkey and baboon. In humans, there is an increase in lens capsule stiffness at the microscale that could be responsible for an increase in lens capsule bulk stiffness.

Contribution of the crystalline lens gradient refractive index to the accommodation amplitude in non-human primates: in vitro studies.

The purpose of this study was to determine the contribution of the gradient refractive index to the change in lens power in hamadryas baboon and cynomolgus monkey lenses during simulated accommodation in a lens stretcher. Thirty-six monkey lenses (1.4-14.1 years) and twenty-five baboon lenses (1.8-28.0 years) were stretched in discrete steps. At each stretching step, the lens back vertex power was measured and the lens cross-section was imaged with optical coherence tomography. The radii of curvature for the lens anterior and posterior surfaces were calculated for each step. The power of each lens surface was determined using refractive indices of 1.365 for the outer cortex and 1.336 for the aqueous. The gradient contribution was calculated by subtracting the power of the surfaces from the measured lens power. In all lenses, the contribution of the surfaces and gradient increased linearly with the amplitude of accommodation. The gradient contributes on average 65 ± 3% for monkeys and 66 ± 3% for baboons to the total power change during accommodation. When expressed in percent of the total power change, the relative contribution of the gradient remains constant with accommodation and age in both species. These findings are consistent with Gullstrand's intracapsular theory of accommodation.

Detection of singlet oxygen luminescence for experimental corneal rose bengal photodynamic antimicrobial therapy.

Rose bengal photodynamic antimicrobial therapy (RB-PDAT) treats corneal infection by activating rose bengal (RB) with green light to produce singlet oxygen (1O2). Singlet oxygen dosimetry can help optimize treatment parameters. We present a 1O2 dosimeter for detection of 1O2 generated during experimental RB-PDAT. The system uses a 520 nm laser and an InGaAs photoreceiver with bandpass filters to detect 1O2 luminescence during irradiation. The system was validated in RB solutions and ex vivo in human donor eyes. The results demonstrate the feasibility of 1O2 dosimetry in an experimental model of RB-PDAT in the cornea.

Rose Bengal Photodynamic Antimicrobial Therapy: A Pilot Safety Study.

PURPOSE: To evaluate the in vivo corneal changes after Rose Bengal photodynamic antimicrobial therapy (RB-PDAT) treatment in New Zealand White rabbits. METHODS: Sixteen rabbits were divided into 5 groups. All groups underwent deepithelialization of an 8 mm diameter area in the central cornea. Group 1: balanced salt solution drops only, group 2: 0.2% RB only, group 3: green light exposure (525 nm, 5.4 J/cm2) only, group 4: 0.1% RB-PDAT, and group 5: 0.1% RB-PDAT. All rabbits were followed clinically. Group 5 rabbits were followed using anterior segment optical coherence tomography (AS-OCT) and clinically. On day 35 after initial treatment, 1 rabbit from group 5 was re-exposed to green light (5.4 J/cm2) to evaluate reactivation of the remaining RB dye, and terminal deoxynucleotyl transferase-mediated UTP-biotin-nick-end labeling assay was performed on corneal cryosections. RESULTS: Complete reepithelization was observed, and corneas remained clear after treatment in all groups. In group 5, AS-OCT revealed a cross-linking demarcation line. AS-OCT showed RB fluorescence and collagen cross-linking in all treated eyes of group 5 animals after 5 weeks of treatment. Photobleached RB retention in the corneal stroma was corroborated by fluorescence confocal microscopy on frozen sections. There was no evidence of a sustained cytotoxic effect through terminal deoxynucleotyl transferase-mediated UTP-biotin-nick-end labeling at 5 weeks. CONCLUSIONS: RB-PDAT with 0.1% RB is a safe procedure. There was no difference clinically and on histopathology compared with control groups. In eyes where RB dye is retained in the corneal stroma after 1 month of treatment, oxidative stress is not evidenced at long term.

Variations in intraocular lens injector dimensions and corneal incision architecture after cataract surgery.

PURPOSE: To evaluate the differences in intraocular lens (IOL) injectors and to assess the effect of IOL insertion on injector tips and eyes after cataract surgery in a rabbit model. SETTING: Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, USA. DESIGN: Experimental study. METHODS: A modified optical comparator was used to measure the tips of 13 IOL injector models to determine the perimeter, tip angle, and cone angle of each. Injectors were analyzed before and after IOL insertion. Surgery was performed on rabbits with 71 IOL injectors of 13 models, and custom gauges were used to determine the incision size before and after surgery. RESULTS: The injector dimensions varied by model; tip diameter, tip angle, and cone angle ranged from 1.44 to 2.12 mm, 29.7 to 66.5 degrees and 0.6 to 10.8 degrees, respectively. The incision size through which surgery was successfully performed also varied by injector model; the initial incision sizes ranged from 2.0 to 2.63 mm. For all injectors, there was wound enlargement after IOL insertion that ranged from a 0.1 to 0.65 mm increase in incision length. CONCLUSIONS: The dimensions and injection systems varied with each IOL injector. All injectors led to postoperative wound stretch after IOL insertion, with no final incision measuring less than 2.0 mm. These findings suggest that the clear cornea incision should have a width corresponding to the injector diameter.

Off-axis optical coherence tomography imaging of the crystalline lens to reconstruct the gradient refractive index using optical methods.

Earlier studies have shown that the gradient index of refraction (GRIN) of the crystalline lens can be reconstructed in vitro using Optical Coherence Tomography (OCT) images. However, the methodology cannot be extended in vivo because it requires accurate measurements of the external geometry of the lens. Specifically, the posterior surface is measured by flipping the lens so that the posterior lens surface faces the OCT beam, a method that cannot be implemented in vivo. When the posterior surface is imaged through the lens in its natural position, it appears distorted by the unknown GRIN. In this study, we demonstrate a method to reconstruct both the GRIN and the posterior surface shape without the need to flip the lens by applying optimization routines using both on-axis and off-axis OCT images of cynomolgous monkey crystalline lenses, obtained by rotating the OCT delivery probe from -45 to +45 degrees in 5 degree steps. We found that the GRIN profile parameters can be reconstructed with precisions up to 0.009, 0.004, 1.7 and 1.1 (nucleus and surface refractive indices, and axial and meridional power law, respectively), the radius of curvature within 0.089 mm and the conic constant within 0.3. While the method was applied on isolated crystalline lenses, it paves the way to in vivo lens GRIN and posterior lens surface reconstruction.

Optical power of the isolated human crystalline lens.

PURPOSE: To characterize the age dependence of isolated human crystalline lens power and quantify the contributions of the lens surfaces and refractive index gradient. METHODS: Experiments were performed on 100 eyes of 73 donors (average 2.8 +/- 1.6 days postmortem) with an age range of 6 to 94 years. Lens power was measured with a modified commercial lensmeter or with an optical system based on the Scheiner principle. The radius of curvature and asphericity of the isolated lens surfaces were measured by shadow photography. For each lens, the contributions of the surfaces and the refractive index gradient to the measured lens power were calculated by using optical ray-tracing software. The age dependency of these refractive powers was assessed. RESULTS: The total refractive power and surface refractive power both showed a biphasic age dependency. The total power decreased at a rate of -0.41 D/y between ages 6 and 58.1, and increased at a rate of 0.33D/y between ages 58.1 and 82. The surface contribution decreased at a rate of -0.13 D/y between ages 6 and 55.2 and increased at a rate of 0.04 D/y between ages 55.2 and 94. The relative contribution of the surfaces increased by 0.17% per year. The equivalent refractive index also showed a biphasic age dependency with a decrease at a rate of -3.9 x 10(-4) per year from ages 6 to 60.4 followed by a plateau. CONCLUSIONS: The lens power decreases with age, due mainly to a decrease in the contribution of the gradient. The use of a constant equivalent refractive index value to calculate lens power with the lens maker formula will underestimate the power of young lenses and overestimate the power of older lenses.

Peripheral Defocus of the Monkey Crystalline Lens With Accommodation in a Lens Stretcher.

Purpose: To characterize the peripheral defocus of the monkey crystalline lens and its changes with accommodation. Methods: Experiments were performed on 15 lenses from 11 cynomolgus monkey eyes (age: 3.8-12.4 years, postmortem time: 33.5 ± 15.3 hours). The tissue was mounted in a motorized lens stretcher to allow for measurements of the lens in the accommodated (unstretched) and unaccommodated (stretched) states. A custom-built combined laser ray tracing and optical coherence tomography system was used to measure the paraxial on-axis and off-axis lens power for delivery angles ranging from -20° to +20° (in air). For each delivery angle, peripheral defocus was quantified as the difference between paraxial off-axis and on-axis power. The peripheral defocus of the lens was compared in the unstretched and stretched states. Results: On average, the paraxial on-axis lens power was 52.0 ± 3.4 D in the unstretched state and 32.5 ± 5.1 D in the stretched state. In both states, the lens power increased with increasing delivery angle. From 0° to +20°, the relative peripheral lens power increased by 10.7 ± 1.4 D in the unstretched state and 7.5 ± 1.6 D in the stretched state. The change in field curvature with accommodation was statistically significant (P < 0.001), indicating that the unstretched (accommodated) lens has greater curvature or relative peripheral power. Conclusions: The cynomolgus monkey lens has significant accommodation-dependent curvature of field, which suggests that the lens asserts a significant contribution to the peripheral optical performance of the eye that also varies with the state of accommodation.

Optomechanical response of human and monkey lenses in a lens stretcher.

PURPOSE: To quantify the forces necessary to change the shape and optical power of human and monkey lenses. METHODS: Cynomolgus monkey (n = 48; age: 3.8-11 years), rhesus monkey (n = 35; age: 0.7-17 years) and human (n = 20, age 8-70 years) eyes obtained postmortem, including the lens, capsule, zonules, ciliary body, and sclera were mounted in an optomechanical lens-stretching system. Starting at zero load, the lenses were symmetrically stretched in a stepwise fashion in 0.25- or 0.5-mm steps. The load, lens diameter, inner ciliary body diameter, and lens power were measured at each step and the diameter- and power-load responses were quantified. RESULTS: The diameter- and power-load responses were found to be linear in the physiologically relevant range of stretching. The average change in cynomolgus, rhesus, and human lens diameter, respectively, was 0.094, 0.109, and 0.069 mm/g in young lenses, and 0.069, 0.067, and 0.036, mm/g in older lenses. For the same lenses, the average change in lens power was -3.73, -2.83, and -1.22 D/g in young lenses and -2.46, -2.16, and -0.49 D/g in older lenses. CONCLUSIONS: The force necessary to change the lens diameter and lens power increases with age in human and monkey lenses. The results agree with the Helmholtz theory of accommodation and with presbyopia theories that predict that the force required to disaccommodate the lens increases with age.

The development of a micro-shunt made from poly(styrene-block-isobutylene-block-styrene) to treat glaucoma.

Glaucoma is the second leading cause of blindness with ∼70 million people worldwide who are blind from this disease. The currently practiced trabeculectomy surgery, the gold standard treatment used to stop the progression of vision loss, is rather draconian, traumatic to the patient and requires much surgical skill to perform. This article summarizes the more than 10-year development path of a novel device called the InnFocus MicroShunt®, which is a minimally invasive glaucoma drainage micro-tube used to shunt aqueous humor from the anterior chamber of the eye to a flap formed under the conjunctiva and Tenon's Capsule. The safety and clinical performance of this device approaches that of trabeculectomy. The impetus to develop this device stemmed from the invention of a new biomaterial called poly(styrene-block-isobutylene-block-styrene), or "SIBS." SIBS is ultra-stable with virtually no foreign body reaction in the body, which manifests in the eye as clinically insignificant inflammation and capsule formation. The quest for an easier, safer, and more effective method of treating glaucoma led to the marriage of SIBS with this glaucoma drainage micro-tube. This article summarizes the development of SIBS and the subsequent three iterations of design and four clinical trials that drove the one-year qualified success rate of the device from 43% to 100%. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 211-221, 2017.

Three-Year Follow-up of a Novel Aqueous Humor MicroShunt.

AIMS: An observational study to determine the safety and efficacy of filtering surgery employing a microlumen aqueous drainage device (InnFocus MicroShunt), used intraoperatively with Mitomycin C, implanted alone or in combination with phacoemulsification. MATERIALS AND METHODS: Single-site, prospective, nonrandomized study of 23 eyes that had failed maximum tolerated glaucoma medication, followed for 3 years. A MicroShunt was implanted ab externo through a needle tract under the limbus, draining aqueous from the anterior chamber to the scleral surface. Prespecified outcome measures include: intraocular pressure (IOP) control, with and without supplemental medication, success rate, medication use, and adverse events. RESULTS: Fourteen patients received the MicroShunt alone and 9 with cataract surgery. At 1 (n=23), 2 (n=22), and 3 (n=22) years of follow-up; the qualified success rate (IOP ≤ 14 mm Hg and IOP reduction ≥ 20%) was 100%, 91%, and 95%; mean medicated IOP was reduced from 23.8 ± 5.3 to 10.7 ± 2.8, 11.9 ± 3.7, and 10.7 ± 3.5 mm Hg, and the mean number of glaucoma medications/patient was reduced from 2.4 ± 0.9 to 0.3 ± 0.8, 0.4 ± 1.0, and 0.7 ± 1.1, respectively. The most common complications were transient hypotony (13%, 3/23) and transient choroidal effusion (8.7%, 2/23), all resolved spontaneously. There were no leaks, infections, migrations, erosions, persistent corneal edema, or serious long-term adverse events. CONCLUSION: Surgery with the InnFocus MicroShunt transscleral aqueous drainage tube with Mitomycin C achieved IOP control in the low teens in most subjects up to 3 years of follow-up with only transient adverse events occurring within the first 3 months after surgery.

The use of poly(styrene-block-isobutylene-block-styrene) as a microshunt to treat glaucoma.

The InnFocus MicroShunt® is a minimally invasive glaucoma drainage microtube used to shunt aqueous humor from the anterior chamber of the eye to a flap formed under the conjunctiva and Tenon's capsule. The safety and clinical performance of this device approaches that of trabeculectomy with mitomycin C, the current 'gold standard' treatment for advanced glaucoma. The invention of a new biomaterial called poly(styrene-block-isobutylene-block-styrene) or 'SIBS' is the enabling factor which led to the success of this product. SIBS is ultrastable with virtually no foreign body reaction in the body, which manifests as clinically insignificant inflammation and capsule formation in the eye. The lack of capsule formation enables unobstructed flow through the 70 µm lumen tube and the achievement of controlled low intraocular pressure, which is important for the management of glaucoma. This article summarizes the integration of SIBS into a glaucoma drainage device and confirms its functionality with clinical success over a 2-year period.

Changes in monkey crystalline lens spherical aberration during simulated accommodation in a lens stretcher.

PURPOSE: The purpose of this study was to quantify accommodation-induced changes in the spherical aberration of cynomolgus monkey lenses. METHODS: Twenty-four lenses from 20 cynomolgus monkeys (Macaca fascicularis; 4.4-16.0 years of age; postmortem time 13.5 ± 13.0 hours) were mounted in a lens stretcher. Lens spherical aberration was measured in the unstretched (accommodated) and stretched (relaxed) states with a laser ray tracing system that delivered 51 equally spaced parallel rays along 1 meridian of the lens over the central 6-mm optical zone. A camera mounted below the lens was used to measure the ray height at multiple positions along the optical axis. For each entrance ray, the change in ray height with axial position was fitted with a third-order polynomial. The effective paraxial focal length and Zernike spherical aberration coefficients corresponding to a 6-mm pupil diameter were extracted from the fitted values. RESULTS: The unstretched lens power decreased with age from 59.3 ± 4.0 diopters (D) for young lenses to 45.7 ± 3.1 D for older lenses. The unstretched lens shifted toward less negative spherical aberration with age, from -6.3 ± 0.7 µm for young lenses to -5.0 ± 0.5 µm for older lenses. The power and spherical aberration of lenses in the stretched state were independent of age, with values of 33.5 ± 3.4 D and -2.6 ± 0.5 µm, respectively. CONCLUSIONS: Spherical aberration is negative in cynomolgus monkey lenses and becomes more negative with accommodation. These results are in good agreement with the predicted values using computational ray tracing in a lens model with a reconstructed gradient refractive index. The spherical aberration of the unstretched lens becomes less negative with age.