Design and Biocompatibility of a Novel, Flexible Artificial Cornea.

Purpose: We sought to introduce the materials, design, and biocompatibility of a flexible and suturable artificial corneal device. Methods: Single-piece, fully synthetic, optic-skirt design devices were made from compact perfluoroalkoxy alkane. The skirt and the optic wall surfaces were lined with a porous tissue ingrowth material using expanded polytetrafluoroethylene. Full-thickness macroapertures around the skirt perimeter were placed to facilitate nutrition of the recipient cornea. Material properties including the skirt's modulus of elasticity and bending stiffness, optic light transmission, wetting behavior, topical drug penetrance, and degradation profile were evaluated. Results: The final prototype suitable for human use has a transparent optic with a diameter of 4.60 mm anteriorly, 4.28 mm posteriorly, and a skirt outer diameter of 6.8 mm. The biomechanical and optical properties of the device closely align with the native human cornea with an average normalized device skirt-bending stiffness of 4.7 kPa·mm4 and light transmission in the visible spectrum ranging between 92% and 96%. No optical damage was seen in the 36 devices tested in fouling experiments. No significant difference was observed in topical drug penetrance into the anterior chamber of the device implanted eye compared with the naïve rabbit eye. Conclusions: The flexibility and biocompatibility of our artificial cornea device may offer enhanced tissue integration and decreased inflammation, leading to improved retention compared with rigid keratoprosthesis designs. Translational Relevance: We have developed a fully synthetic, flexible, suturable, optic-skirt design prototype artificial cornea that is ready to be tested in early human feasibility studies.

Peripheral defocus of monofocal intraocular lenses.

PURPOSE: To quantify the angular dependence of monofocal intraocular lens (IOL) power. SETTING: Ophthalmic Biophysics Laboratory, Kallam Anji Reddy campus, L V Prasad Eye Institute, Hyderabad, India. DESIGN: Laboratory study. METHODS: Experiments were performed on IOLs from 2 different manufacturers (APPALENS 207, Appasamy Associates and SN60WF, Alcon Laboratories, Inc.). IOL powers ranged from 17 to 25 diopters (D). The IOLs were mounted in a fluid-filled chamber, and the on-axis and off-axis powers were measured using a laser ray tracing system over the central 3 mm zone with delivery angles ranging from -30 to +30 degrees in 5-degree increments. The position of the best focus was calculated for each IOL at each angle. The angular dependence of IOL power was compared with theoretical predictions. RESULTS: Peripheral defocus increased significantly with increasing incidence angle and power. The peripheral defocus at ±30 degrees increased from 5.8 to 8.5 D when the power increased from 17.5 to 24.5 D for APPALENS 207 and from 4.9 to 7.4 D when the power increased from 17 to 25 D for SN60WF. The mean difference between the measured and theoretical tangential power at ±30 degrees was 0.50 ± 0.16 D for the APPALENS 207 and -0.40 ± 0.10 D for the SN60WF, independent of IOL power. CONCLUSIONS: IOLs introduce a significant amount of peripheral defocus which varies significantly with IOL power and design. Given that peripheral defocus is related to lens power, replacement of the crystalline lens (approximately 24 D) with an IOL will produce a significant difference in peripheral defocus profile after surgery.

Twelve-Month Clinical and Histopathological Performance of a Novel Synthetic Cornea Device in Rabbit Model.

Purpose: To report the biological stability and postoperative outcomes of a second-generation, single-piece, flexible synthetic cornea in a rabbit model. Methods: Device materials and design were amended to enhance biointegration. Optic skirt design devices were made from compact perfluoroalkoxy alkane with porous expanded polytetrafluoroethylene ingrowth surface overlying the skirt and optic wall. Sixteen devices were implanted into intrastromal pocket in rabbit eyes. Rabbits were randomly assigned to 6- and 12-month follow-up cohorts (n = 8 in each) postoperatively. Monthly examinations and optical coherence tomography assessed cornea-device integration, iridocorneal angle, optic nerve, and retina. Results: There were no intraoperative complications. All devices were in situ at exit, with clear optics. No retroprosthetic membrane, glaucoma, cataract formation, or retinal detachment was observed. Two rabbits in the 6-month group had mild, focal anterior lamella thinning without retraction adjacent to the optic near tight sutures. Three postoperative complications occurred in the 12-month group. One rabbit diagnosed with endophthalmitis was euthanized on day 228. Mild sterile focal retraction of anterior lamella occurred in two rabbits, which were terminated on days 225 and 315. Light microscopic examination of enucleated globes demonstrated fibroplasia with new collagen deposition into the porous scaffold without significant inflammation, encapsulation, or granuloma formation. Conclusions: Clinical evaluations, imaging, and histopathological findings indicate favorable outcomes of this synthetic corneal device in a rabbit model. Early feasibility studies in humans are being planned. Translational Relevance: Favorable 12-month results of the device in rabbits demonstrate vision-restoring potential in corneally blind individuals at high risk of failure with donor keratoplasty.

In vivo measurement of the attenuation coefficient of the sclera and ciliary muscle.

We acquired 1325 nm OCT images of the sclera and ciliary muscle of human subjects. The attenuation coefficients of the sclera and ciliary muscle were determined from a curve fit of the average intensity profile of about 100 A-lines in a region of interest after correction for the effect of beam geometry, using a single scattering model. The average scleral attenuation coefficient was 4.13 ± 1.42 mm-1 with an age-related decrease that was near the threshold for statistical significance (p = 0.053). The average ciliary muscle attenuation coefficient was 1.72 ± 0.88 mm-1, but this value may be an underestimation due to contributions from multiple scattering. Overall, the results suggest that inter-individual variations in scleral attenuation contribute to variability in the quality of transscleral OCT images of the ciliary muscle and the outcome of transscleral laser therapies.

Relationship of the cornea and globe dimensions to the changes in adult human crystalline lens diameter, thickness and power with age.

It is well known that human crystalline lens shape, dimensions and optical properties change throughout life and influence whole eye refraction. However, it is not clear if lens properties are associated with other ocular parameters. The purpose of the present study was to investigate the relationship of corneal and external globe dimensions with adult lens diameter (LD), lens thickness (LT) and lens power (LP) in order to determine if external factors influence lens properties. Postmortem human eyes (n = 66, age = 20-78 years) were obtained from the Ramayamma International Eye Bank, Hyderabad, India. Globe antero-posterior length (GAPL) and mean (average of horizontal and vertical) diameters of cornea (MCD) and globe (MGD) were measured using digital calipers. Eyes were dissected to produce ocular structures that contain the lens maintained in its accommodating framework, including intact zonules, ciliary body and sections of sclera. Specimens were mounted in a mechanical lens stretching system. LD, LT and LP were measured using high magnification retro-illumination photography, slit illumination photography and Scheiner principle-based optical system respectively in the unstretched (accommodated) state. Relationships between external globe and corneal dimensions and LD, LT or LP were assessed by multiple regression analysis. Age (0.012 ± 0.003 mm/year; p<0.001) and GAPL (0.185 ± 0.045 mm/mm; p<0.001) were significant (p<0.0001) predictors of LD. After adjusting for age-related increases, LD appears to be positively correlated with GAPL. Age (0.010 ± 0.004 mm/year; p = 0.009) and GAPL (-0.143 ± 0.060 mm/mm; p = 0.02) were significant (p = 0.001) predictors of LT. After adjusting for the age-related increase, LT appears to be negatively correlated with GAPL. Only age was a significant predictor of LP (-0.26 ± 0.04 D/year; p<0.001). The results suggest that, apart from aging, lens diameter and thickness are dependent on the anteroposterior length of the eye globe. Lens power is not influenced by globe dimensions.

Isolated human crystalline lens three-dimensional shape: A comparison between Indian and European populations.

There have been many studies on lens properties in specific populations (e.g. in China, Europe, Singapore, etc.) some of which suggest there may be differences between populations. Differences could be caused by ethnic or environmental influences or experimental procedures. The purpose of this study is to evaluate if any differences exist between Indian and European populations in the central geometric and full shape properties of human lenses. Two custom-developed spectral domain optical coherence tomography systems were used to acquire the crystalline lens geometry: one in India (69 lenses from 59 donors) and the other in Spain (24 lenses from 19 donors). The steps for obtaining accurate 3-D models from optical coherence tomography raw images comprised of image segmentation, fan and optical distortion correction, tilt removal and registration. The outcome variables were lens equatorial diameter, lens thickness, anterior and posterior lens thicknesses and their ratio, central radius of curvature of the anterior and posterior lens surfaces, lens volume and lens surface area. A mixed effects model by maximum likelihood estimation was used to evaluate the effect of age, population and their interaction (age*population) on lens parameters. After adjusting for age, there were no population differences observed in anterior and posterior radii of curvature, equatorial diameter, lens thickness, anterior and posterior lens thicknesses and their ratio, volume and surface area (all p ≥ 0.08). There was also no effect of the interaction term on anterior and posterior radii of curvature, equatorial diameter, lens thickness, anterior and posterior lens thicknesses and their ratio, volume and surface area (all p ≥ 0.06). All central geometric and full shape parameters appeared to be comparable between the European and Indian populations. This is the first study to compare geometric and full shape lens parameters between different populations in vitro.

Morphometric analysis of in vitro human crystalline lenses using digital shadow photogrammetry.

There is a great need for accurate biometric data on human lenses. To meet this, a compact tabletop optical comparator, the minishadowgraph, was built for measuring isolated eye lens shape and dimensions while the lens was fully immersed in supporting medium. The instrument was based around a specially designed cell and an illumination system which permitted image recording in both sagittal and equatorial (coronal) directions. Data were acquired with a digital camera and analyzed using a specially written MATLAB program as well as by manual measurements in image analysis software. The possible effect of lens orientation and gravity on the dimensions was examined by measuring dimensions with anterior or posterior surfaces up and by measuring lenses with calipers after removal from the minishadowgraph cell. Dimensions, curvatures and shape factors were obtained for 134 fully accommodated lenses ranging in age from birth to 88 years postnatal. Of these, 41 were from donors aged under 20 years, ages which are generally of limited availability. Thickness and diameter showed the same age-related trends described in previous studies but, for the lenses measured in air, age-dependent differences were observed in thickness (-5 to 0%) and diameter (+5 to 0%), consistent with gravitational sag. Anterior and posterior radii of curvature of the central 3 or 6 mm, depending on lens diameter, increase with age, with the anterior increase greater than the posterior. The anterior surface shape of the neonatal lens is that of a prolate ellipse and the posterior, an oblate ellipse. Both surfaces become hyperbolic after age 20. The data presented here on dimensions, shape and sagging will be of great value in assessing age-related changes in the optical and mechanical performance of the lens. In particular, the comprehensive data set from donors aged under 20 years provides a unique and valuable insight to the changes in size and shape during the early dynamic growth period of the lens.

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.

Interfacial Behavior of Fumonisin B1 Toxin and Its Degradation on the Membrane.

Fumonisin B1 (FB1), the most abundant component of the fumonisin family, is highly responsible for fungal infections. In this paper, our main aim is to study the surface chemistry and spectroscopic properties of the FB1 molecule and observe the impact of green LED light on the FB1 Langmuir monolayer. From the surface chemistry and spectroscopic studies, we found that the FB1 molecule forms a self-assembled Langmuir monolayer which is sufficient to mimic its interaction with the corneal tissues. The irradiation of green LED light on the FB1 Langmuir monolayer showed the degradation of the FB1 when compared to that in the absence of light. This observation reveals that FB1 molecules lose their tendency to stay as a Langmuir monolayer. The degradation observed on the interface was compared with the bulk phase of FB1. The bulk phase observation also indicated the degradation tendency which reinforced the observed interfacial property of FB1.

Automated instrument designed to determine visual photosensitivity thresholds.

The Ocular Photosensitivity Analyzer (OPA), a new automated instrument to quantify the visual photosensitivity thresholds (VPT) in healthy and light sensitive subjects, is described. The OPA generates light stimuli of varying intensities utilizing unequal ascending and descending steps to yield the VPT. The performance of the OPA was evaluated in healthy subjects, as well as light sensitive subjects with achromatopsia or traumatic brain injury (TBI). VPT in healthy, achromatopsia, and TBI subjects were 3.2 ± 0.6 log lux, 0.5 ± 0.5 log lux, and 0.4 ± 0.6 log lux, respectively. Light sensitive subjects manifested significantly lower VPT compared to healthy subjects. Longitudinal analysis revealed that the OPA reliably measured VPT in healthy subjects.

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 patient's 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 patient's examination via local area network, Internet, and satellite. TRANSLATIONAL RELEVANCE: The robotic remotely controlled stereo slit lamp system enables remote examination of human subjects.

Long-term outcomes of the aphakic snap-on Boston type I keratoprosthesis at the Bascom Palmer Eye Institute.

PURPOSE: To determine the indications, long-term clinical and visual outcomes, and complications of the aphakic snap-on type I Boston keratoprosthesis (KPro). DESIGN: Retrospective, non-comparative case series. METHODS: Forty-five eyes of 43 patients with type I aphakic snap-on KPros with at least 1 year of follow-up were included. The past medical histories, preoperative indications, best-corrected visual acuities (BCVAs), postoperative complications, and retention rates were analyzed. RESULTS: The most common indication for KPro implantation was a failed corneal graft (89%). The mean preoperative BCVA was count fingers-hand motion (2.14±0.45 logarithm of minimum angle of resolution [logMAR]), which initially improved to 20/200 (1.04±0.85 logMAR; P<0.0001). At the last examination, 24 eyes (53%) maintained some visual gain, 22% retained their preoperative visual acuity, and 24% lost vision due to postoperative events and underlying ocular comorbidities. Postoperative complications included retroprosthetic membranes (8/45, 18%), corneal melts (5/45, 11%), glaucoma progression (6/45, 13%), and endophthalmitis or sterile vitritis (6/45, 13%). The KPro retention rate was 89%, with a mean follow-up of 51 months. The mean BCVA at the last visit was 20/1,400 (1.82±0.92 logMAR). CONCLUSION: Most patients experienced improved visual acuity after the implantation of the aphakic, snap-on type I KPro; however, the visual gains were not sustained over time, correlating with the onset of postoperative complications.

New Methods for Quantification of Visual Photosensitivity Threshold and Symptoms.

PURPOSE: Visual photosensitivity is a common symptom difficult to measure and diagnose, and is found in many ocular and neurological disorders. We developed two novel reproducible quantitative assessments of visual photosensitivity. METHODS: We designed and built the ocular photosensitivity analyzer (OPA), an automated instrument to determine light intensity visual photosensitivity threshold (VPT), and developed the Visual Light Sensitivity Questionnaire-8 (VLSQ-8), an eight-question survey to assess the presence and severity of photosensitivity symptoms. We evaluated the test-retest variability and obtained normative values of these two approaches in 35 healthy normal subjects, distributed evenly over five age groups from eight to 60 years. Each subject underwent two test sessions, each with VLSQ-8, eye examination, and OPA, four weeks apart, between April 2015 and June 2016. RESULTS: Log-transformed VPTs (log10lux) and VLSQ-8 results were highly reproducible between the two sessions (VPT intraclass correlation coefficient [ICC] = 0.86; 95% confidence interval [CI] = 0.71-0.93; binocular testing, VLSQ-items ICC range = 0.53-0.87). No consistent significant differences in VPTs were found with monocular (P = 0.053, session 1) or binocular (P = 0.26) testing. Subjects in age group >30 to 40 years had significantly higher VPTs than those in other age groups (P ≤ 0.011) except the >40 to 50 years age group (P = 0.11). Photosensitivity symptoms assessed by the VLSQ-8 generally were low and highly reproducible with ≥88% of responses between the 2 sessions being within one category of each other. CONCLUSIONS: Our results provide reliability data and normative results toward validation of two novel approaches to quantify visual photosensitivity and provide support for their potential use in ocular and neurologic conditions as well as in clinical trials. TRANSLATIONAL RELEVANCE: The new quantitative photosensitivity approaches are potential measures to characterize disease severity, monitor disease progression, and evaluate treatment efficacy.

A new, specular reflection-based, precorneal tear film stability measurement technique in a rabbit model: viscoelastic increases tear film stability.

PURPOSE: To develop a safe, noninvasive, noncontact, continuous in vivo method to measure the dehydration rate of the precorneal tear film and to compare the effectiveness of a viscoelastic agent in maintaining the precorneal tear film to that of a balanced salt solution. METHODS: Software was designed to analyze the corneal reflection produced by the operating microscope's coaxial illumination. The software characterized the shape of the reflection, which became distorted as the precorneal tear film evaporated; characterization was accomplished by fitting an ellipse to the reflection and measuring its projected surface area. Balanced salt solution Plus (BSS+) and a 2% hydroxypropylmethylcellulose viscoelastic were used as the test agents. The tear film evaporation rate was characterized and compared over a period of 20 minutes in 20 eyes from 10 New Zealand white rabbits. RESULTS: The ellipse axes ratio and surface area were found to decrease initially after each application of either viscoelastic or BSS+ and then to increase linearly as the tear film began to evaporate (P < 0.001) for eyes treated with BSS+ only. Eyes treated with BSS+ required 7.5 ± 2.7 applications to maintain sufficient corneal hydration during the 20-minute test period, whereas eyes treated with viscoelastic required 1.4 ± 0.5 applications. The rates of evaporation differed significantly (P < 0.043) between viscoelastic and BSS+. CONCLUSIONS: The shape and surface area of the corneal reflection are strongly correlated with the state of the tear film. Rabbits' corneas treated with viscoelastic remained hydrated significantly longer than corneas treated with BSS+.

Differential flow rate of commercially available triamcinolone with and without preservative through small-gauge needles.

OBJECTIVE: To compare the flow rate through different gauge needles of triamcinolone acetonide with benzyl alcohol (TABA) versus preservative-free triamcinolone acetonide injectable suspension (TAIS). MATERIALS AND METHODS: Experimental injections of 1 mL of TABA or TAIS were performed through a 27-, 30-, or 32-gauge needle. A piezoelectric pressure transducer connected to a personal computer was placed between the syringe and needle to record the force-time relationship and assess the flow rate (mL/s). Measurements were performed in triplicate. RESULTS: Flow rates were similar between preparations using a 27-gauge needle. Using a 30-gauge needle, the flow rate was 0.058 mL/s for TABA and 0.178 mL/s for TAIS. Using a 32-gauge needle, no flow was sustained by TABA, whereas the flow rate of TAIS was 0.114 mL/s (P < .05). CONCLUSION: TAIS can be injected through a 32-gauge needle without the risk of obstruction. Occlusions were seen with TABA using the 30- and 32-gauge needles.

Local ischemia and increased expression of vascular endothelial growth factor following ocular dissemination of Mycobacterium tuberculosis.

The pathogenesis of intraocular tuberculosis remains poorly understood partly due to the lack of adequate animal models that accurately simulate human disease. Using a recently developed model of ocular tuberculosis following aerosol infection of guinea pigs with Mycobacterium tuberculosis, we studied the microbiological, histological, and clinical features of intraocular tuberculosis infection. Viable tubercle bacilli were cultivated from all eyes by Day 56 after aerosol delivery of ∼200 bacilli to guinea pig lungs. Choroidal tuberculous granulomas showed reduced oxygen tension, as evidenced by staining with the hypoxia-specific probe pimonidazole, and expression of vascular endothelial growth factor (VEGF) was detected in the retinal pigment epithelium (RPE) and photoreceptors. Fundoscopic examination of M. tuberculosis-infected guinea pig eyes revealed altered vascular architecture and chorioretinal hemorrhage by Day 56 after infection. This model may be useful in further elucidating the pathogenesis of ocular tuberculosis, as well as in developing tools for diagnosis and assessment of antituberculosis treatment responses in the eye.