Derek Nankivil

High Refractive Index Polysiloxane as Injectable, In Situ Curable Accommodating Intraocular Lens

Functionalised siloxane macromonomers, with properties designed for application as an injectable, in situ curable accommodating intraocular lens (A-IOL), were prepared via re-equilibration of a phenyl group-containing polysiloxane of very high molecular weight with octamethylcyclotetrasiloxane (D₄) and 2,4,6,8-tetra(n-propyl-3-methacrylate)-2,4,6,8-tetramethyl-cyclotetrasiloxane (D₄(AM)) in toluene using trifluoromethanesulfonic acid as a catalyst. Hexaethyldisiloxane was used as an end group to control the molecular weight of the polymer. The generated polymers had a consistency suitable for injection into the empty lens capsule. The polymers contained a low ratio of polymerisable groups so that, in the presence of a photo-initiator, they could be cured on demand in situ within 5 min under irradiation of blue light to form an intraocular lens within the lens capsule. All resulting polysiloxane soft gels had a low elastic modulus and thus should be able to restore accommodation. The pre-cure viscosity and post-cure modulus of the generated polysiloxanes were controlled by the end group and D₄(AM) concentrations respectively in the re-equilibration reactions. The refractive index could be precisely controlled by adjusting the aromatic ratio in the polymer to suit such application as an artificial lens. Lens stretching experiments with both human and non-human primate cadaver lenses of different ages refilled with polysiloxane polymers provided a significant increase in amplitude of accommodation (up to 4 D more than that of the respective natural lens). Both in vitro cytotoxicity study using L929 cell lines and in vivo biocompatibility study in rabbit models demonstrated the non-cytotoxicity and ocular biocompatibility of the polymer.

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 Gullstrands intracapsular theory of accommodation.

Age-dependence of the optomechanical responses of ex vivo human lenses from India and the USA, and the force required to produce these in a lens stretcher: the similarity to in vivo disaccommodation

The purpose of this study was to study the age-dependence of the optomechanical properties of human lenses during simulated disaccommodation in a mechanical lens stretcher, designed to determine accommodative forces as a function of stretch distance, to compare the results with in vivo disaccommodation and to examine whether differences exist between eyes harvested in the USA and India. Postmortem human eyes obtained in the USA (n=46, age=6-83 years) and India (n=91, age=1 day-85 years) were mounted in an optomechanical lens stretching system and dissected to expose the lens complete with its accommodating framework, including zonules, ciliary body, anterior vitreous and a segmented rim of sclera. Disaccommodation was simulated through radial stretching of the sectioned globe by 2mm in increments of 0.25 mm. The load, inner ciliary ring diameter, lens equatorial diameter, central thickness and power were measured at each step. Changes in these parameters were examined as a function of age, as were the dimension/load and power/load responses. Unstretched lens diameter and thickness increased over the whole age range examined and were indistinguishable from those of in vivo lenses as well as those of in vitro lenses freed from zonular attachments. Stretching increased the diameter and decreased the thickness in all lenses examined but the amount of change decreased with age. Unstretched lens power decreased with age and the accommodative amplitude decreased to zero by age 45-50. The load required to produce maximum stretch was independent of age (median 80 mN) whereas the change in lens diameter and power per unit load decreased significantly with age. The age related changes in the properties of human lenses, as observed in the lens stretching device, are similar to those observed in vivo and are consistent with the classical Helmholtz theory of accommodation. The response of lens diameter and power to disaccommodative (stretching) forces decreases with age, consistent with lens nuclear stiffening.

Role of the lens capsule on the mechanical accommodative response in a lens stretcher.

PURPOSE To determine whether changes in elastic properties of the lens capsule ex vivo with age contribute to the forces necessary for accommodation. METHODS Postmortem human (n = 22; age average: 41 +/- 17 years; range: 6-7) and cynomolgus monkey (n = 19; age average: 7.7 +/- 1.8 years, range: 4.2-10) tissues including the lens, capsule, zonules, ciliary body, and sclera were mounted in an optomechanical lens-stretching system. Starting at 0 load, the sclera was symmetrically stretched to 2 mm in 0.25-mm steps at a speed of 0.1 mm x s(-1). The load and lens diameter were measured at each step. The lens contents were removed through a mini-capsulorhexis. The stretching cycles were repeated on the empty capsular bag. The forces necessary to stretch the natural lens and empty bag were quantified as a function of age and compared. RESULTS The force needed to stretch the empty lens capsule was independent of age (human, 2.6-34.9 g/mm [25.2-342.7 mN/mm]; monkey, 8.2-21.3 g/mm [80.3-208.6 mN/mm]). The ratio of the force necessary to stretch the empty lens capsule to the force necessary to stretch the natural lens decreased with age in the human and monkey lenses (P = 0.003, P = 0.72, respectively). CONCLUSIONS The mechanical properties of the empty lens capsule assessed ex vivo in a lens stretcher remain constant with age, suggesting that the changes in elasticity of the lens capsule do not play a significant role in presbyopia. In young eyes, the lens capsule determines the force necessary to stretch the whole lens. The age-related increase in force needed to stretch the lens is due to changes in the lens contents.

Effect of Anterior Zonule Transection on the Change in Lens Diameter and Power in Cynomolgus Monkeys during Simulated Accommodation

PURPOSE To quantify the role of anterior zonular tension on the optomechanical lens response during simulation of accommodation in primates. METHODS Postmortem cynomolgus monkey eyes (n = 14; age range, 3.0-11.5 years) were dissected leaving intact the lens, zonules, ciliary body, hyaloid membrane, anterior vitreous, and a scleral rim. The lens was mounted in a lens-stretching system and stretched radially in step-wise fashion. The load, and the lens diameter and power were measured at each step and the diameter- and power-load relationships were quantified. The anterior zonular fibers were then transected, and the experiment was repeated. The equatorial lens diameter and lens optical power before and after zonular transection were compared. RESULTS Stretching increased the lens diameter by 0.25 +/- 0.09 mm (median +/- interquartile range) before and 0.25 +/- 0.19 mm after zonular transection. Stretching decreased the lens power by 13.0 +/- 6.5 D before and 10.6 +/- 8.0 D after zonular transection. The load required to change the diameter of the lens by 1 mm decreased from 18.8 +/- 10.7 g before to 15.0 +/- 7.8 g after zonular transection. The absolute change in power per gram of loading decreased from 2.5 +/- 1.1 before to 2.0 +/- 1.2 D after zonular transection. CONCLUSIONS The cynomolgus monkey lens retains a significant fraction of its accommodative ability after transection of the anterior zonules in simulated accommodation experiments.

Measurement of Crystalline Lens Volume During Accommodation in a Lens Stretcher

PURPOSE To determine if the lens volume changes during accommodation. METHODS The study used data acquired on 36 cynomolgus monkey lenses that were stretched in a stepwise fashion to simulate disaccommodation. At each step, stretching force and dioptric power were measured and a cross-sectional image of the lens was acquired using an optical coherence tomography system. Images were corrected for refractive distortions and lens volume was calculated assuming rotational symmetry. The average change in lens volume was calculated and the relation between volume change and power change, and between volume change and stretching force, were quantified. Linear regressions of volume-power and volume-force plots were calculated. RESULTS The mean (± SD) volume in the unstretched (accommodated) state was 97 ± 8 mm3. On average, there was a small but statistically significant (P = 0.002) increase in measured lens volume with stretching. The mean change in lens volume was +0.8 ± 1.3 mm3. The mean volume-power and volume-load slopes were -0.018 ± 0.058 mm3/D and +0.16 ± 0.40 mm3/g. CONCLUSIONS Lens volume remains effectively constant during accommodation, with changes that are less than 1% on average. This result supports a hypothesis that the change in lens shape with accommodation is accompanied by a redistribution of tissue within the capsular bag without significant compression of the lens contents or fluid exchange through the capsule.

The precision of ophthalmic biometry using calipers

OBJECTIVE The purpose of the study is to determine the precision of whole globe and cornea measurements acquired using calipers, and to quantify the intraoperator and interoperator variance. DESIGN Experimental study. PARTICIPANTS Ten human donor eyes. METHODS Ten human eyes (donor age, 16-54 years) were obtained between 18.5 and 66.5 hours postmortem. The horizontal and vertical diameters and the anteroposterior length of the globe were measured using a digital Vernier caliper. The horizontal and vertical diameters of the cornea were measured using both a digital Vernier caliper and a Castroviejo caliper. The measurements were performed by 3 operators with 5 repeat measurements for each dimension. RESULTS No significant differences were observed between measurements of globe anteroposterior length, horizontal diameter, and vertical diameter. Horizontal corneal diameter was greater than vertical diameter with all instruments and all operators. Variability of either instrument did not change with measurement object scale, and was similar across all operators. No significant differences were observed between the variabilities of the 2 devices. The mean intraoperator SD was 0.127 ± 0.023 mm with the digital caliper and 0.094 ± 0.056 mm with the Castroviejo caliper. CONCLUSIONS The precision of commercially available calipers in ophthalmic biometry measurements is limited to approximately 0.1 mm.

The Zonules Selectively Alter the Shape of the Lens During Accommodation Based on the Location of Their Anchorage Points

PURPOSE To determine the role of anterior and posterior zonular tension on the optomechanical lens response during accommodation simulation. METHODS Ten eyes from nine hamadryas baboons (4.9 ± 0.7 years) and 20 eyes from 18 cynomolgus monkeys (5.4 ± 0.3 years) were dissected, leaving the lens, zonules, ciliary body, hyaloid membrane, anterior vitreous, and a segmented scleral rim intact. The lens preparation was mounted in a lens stretcher, and the outer scleral shell was displaced radially in a stepwise fashion. The load, lens, and ciliary body diameters, lens power, lens thickness, and the anterior and posterior radius of curvature were measured during stretching. The zonular fibers attached to either the posterior or anterior lens surface were then carefully transected and the experiment was repeated. Zonular transection was confirmed in four eyes via laser scanning confocal microscopy after immunostaining. The effect of zonular transection on the tissue response to stretching was quantified. RESULTS Without anterior zonules, 48% and 97% of the changes in anterior and posterior radii are retained. Without posterior zonules, 81% and 67% of the changes in anterior and posterior radii are retained. The changes in lens shape were reduced after transecting either the anterior or posterior zonules; however, both surfaces still changed shape. CONCLUSIONS While either the anterior or posterior zonules alone are capable of changing the shape of both lens surfaces, the anterior zonules have a greater effect on the anterior lens surface, and the posterior zonules have a greater effect on the posterior lens surface.

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.

Robotic remote controlled stereo slit lamp

Purpose Our purpose was to develop a robotic remotely operated stereo slit lamp system allowing three-dimensional stereo viewing and recording of the patients examination via local area network, Internet, and satellite. Methods A commercial slit lamp was modified to accept motors and servos to permit control of all optical and mechanical components of the device. The custom graphical user interface with dual high-resolution real-time stereoscopic imaging, control/position indicators, overview video, and audio were transmitted via local area network, Internet, and satellite. Under University of Miami Institutional Review Board authorization, Internet connectivity enabled multiple examiners to simultaneously view and control the slit lamp and to collaboratively discuss diagnosis and treatment options. The remote clinicians used a tablet, laptop, or desktop computer to view and control the slit lamp. Results The network, Internet, satellite-connected system was controllable from the United States, Europe, and Canada while acquiring high-resolution, real-time video in all subjects. Control of the slit lamp through Ethernet, WiFi, and 4G exhibited total system latencies of 464 ± 58, 483 ± 64, and 870 ± 66 milliseconds when transmitting within the continent, and Ethernet control exhibited a latency of 606 ± 130 milliseconds when transmitting between continents. High- and low-magnification images of healthy volunteers were acquired by a remote clinician. Conclusions The robotic remotely operated stereo slit lamp system allows three-dimensional stereo viewing and recording of the patients examination via local area network, Internet, and satellite. Translational Relevance The robotic remotely controlled stereo slit lamp system enables remote examination of human subjects.