Thom Terwee

7.1 T MRI to Assess the Anterior Segment of the Eye

PURPOSE Visualization of the anterior segment and biometric evaluation of the entire crystalline lens pose significant challenges for imaging techniques because of tissue-induced distortion artifacts. The present study was conducted to demonstrate the advantages of high-resolution magnetic resonance imaging (micro-MRI) for visualizing the anterior segment. METHODS High-resolution MR ocular images were acquired on an ultra-high-field MR unit using a two-channel coil with four coil elements and T(2)-weighted turbo spin echo sequences ex vivo in pig, rabbit, monkey, and human donor eyes and in vivo in rabbits. Tissue heating, reproducibility, and signal-to-noise ratio were investigated in vivo. Monkey eye lens thickness (LT) was also measured using A-scan ultrasonography (US). RESULTS Anterior segment details of phakic eyes were obtained ex vivo (pig, rabbit, monkey, and human donor eyes) with pixel matrix size 512 × 512 (in-plane resolution 80 × 80 μm) and in vivo (rabbit eyes) with pixel matrix size 320 × 320 (in-plane resolution 125 × 125 μm). Complete quantification of lens dimensions as they correlate with the sulcus-sulcus and angle-angle plane can be performed. In LT determinations in monkey eyes, no significant difference was detected between micro-MRI and A-scan US (P > 0.05, Mann-Whitney U test). Biometric analysis of one pseudophakic monkey eye confirmed the absence of relevant distortion artifacts. CONCLUSIONS Micro-MRI allows ex vivo and in vivo visualization and quantification of the spatial arrangement of the anterior eye segment. Imaging of the retroiridian region, including the entire crystalline lens, overcomes a number of major limitations in the quantitative evaluation of the anterior segment.

Relation between injected volume and optical parameters in refilled isolated porcine lenses

Purpose:  This study was performed to elucidate the correlation between added lens refill material and enhanced lens power as well as the correlation between lens refilling volume and accommodative amplitude as determined by equatorial stretching of ex vivo refilled pigs’ lenses.

Relationship between contrast sensitivity and spherical aberration Comparison of 7 contrast sensitivity tests with natural and artificial pupils in healthy eyes

PURPOSE: To find a contrast sensitivity test that can be used clinically to evaluate interventions aimed at minimizing spherical aberration and determine the circumstances under which these tests should be performed. SETTING: Laboratory of Experimental Ophthalmology, University of Groningen, Groningen, The Netherlands. METHODS: Contrast sensitivity tests were performed using 2 experimental designs. Design 1 was with a natural pupil under mesopic and photopic conditions. Design 2 was with a 5.0 mm artificial pupil after cycloplegia under photopic conditions only. Two computerized tests (vertical sine‐modulated gratings [VSG] and Holladay circular sine‐modulated patterns [HACSS]) and 5 chart tests (Pelli‐Robson, acuity‐measuring letter charts at low contrast [2.5% and 10%], VectorVision, and edge contrast sensitivity) were used. Spherical aberration was assessed with a Hartmann‐Shack wavefront analyzer. RESULTS: Forty‐nine healthy subjects aged 20 to 35 years (n = 24) and 55 to 70 years (n = 25) participated. Design 2 showed a significant relationship between contrast sensitivity and spherical aberration with the HACSS at 3 cycles per degree (cpd) (P = .03) and 6 cpd (P = .01) and with the VSG at 6 cpd (P = .01). Design 1 yielded no significant relationships. CONCLUSIONS: Using an artificial pupil, a relationship between contrast sensitivity and spherical aberration was established with the VSG and HACSS tests but not with the chart tests. No test showed a relationship using natural pupils under either lighting condition. Chart tests are unsuitable for uncovering contrast sensitivity differences related to differences in spherical aberration, as typically found in healthy phakic eyes.

Effect of infusion bottle height on lens power after lens refilling with and without a plug

Purpose: To evaluate the influence of intraoperative infusion bottle height on the power of refilled pig lenses. Setting: Research Laboratory, Pharmacia Intraocular Lens Manufacturing Plant, Groningen, The Netherlands. Methods: This study comprised 2 groups of pig eyes. In 1 group, the lens was refilled with silicone oil using a plug to close the capsulorhexis; in the other group, no plug was used. The anterior chamber depth, lens thickness, and vitreous chamber depth were measured by A‐scan ultrasound. The total refraction was measured with a Hartinger refractometer. Measurements were performed with the infusion bottle at 0 cm, 25 cm, 50 cm, 75 cm, and 100 cm above eye level. Calculations using a model eye were performed to evaluate the change in lens power based on empirical data. Results: The mean change in the power of refilled lenses caused by varying the height of the infusion bottle was 1.8 diopters. Lenses refilled with a plug had a thickness similar to that of natural lenses. Lenses refilled without a plug were significantly thinner (P<.05). The power of lenses refilled with a plug was significantly higher that of lenses refilled without a plug (P<.05). Conclusions: During lens refilling, infusion bottle height influenced the resulting lens power. Using a plug to close the capsulorhexis resulted in refilled lens dimensions similar to those of the natural lens.

Prevention of capsular opacification after accommodative lens refilling surgery in rabbits

Silicone gel-like polymers have been proposed to replace the cataractous lens and therewith restore both vision and accommodation. Lens replacement is associated with opacification of the capsular bag due to the lens epithelial cell response. In this study, the in vivo effectiveness of a 5 min treatment with actinomycin D and/or cycloheximid to prevent the development of capsular opacification after filling the capsular bag with a silicone polymer as an accommodating lens was studied. It was found that treating the inside of the capsular bag with a solution containing actinomycin D reduced the development of visible capsular opacification for three months. In some animals, the lens capsules were completely clear, indicating the potential of this method. Side effects of the treatment in the form of visible cornea opacification occurred and ranged from mild to severe in some animals, while in other animals no toxicity occurred. This indicates that a safe application of the cytotoxic substances is feasible. In view of the side effects and the fact that not all lens capsules of the animals treated with actinomycin D were clear, improvements in the methods used are necessary and seem to be possible.

In vivo 7.1 T magnetic resonance imaging to assess the lens geometry in rabbit eyes 3 years after lens-refilling surgery

PURPOSE: To evaluate the utility of high‐resolution magnetic resonance imaging (MRI) in assessing the normal and refilled lens geometry in rabbits after lens‐refilling surgery. SETTING: University of Rostock, Rostock, Germany. DESIGN: Experimental study. METHODS: High‐resolution ocular MRIs were acquired (7.1 T ClinScan) using a 2‐channel coil with 4 coil elements and T2‐weighted turbo spin‐echo sequences (slice thickness 700 μm, field of view 40 mm × 40 mm) in rabbits after lens refilling surgery combined with intraoperative treatment to prevent lens epithelial cell proliferation. Single slices were used to assess the refilled lenses 3 years postoperatively. RESULTS: The entire geometry (cross‐sectional area, radius of curvature, axial and equatorial diameters) of the crystalline and refilled lenses was visualized by in vivo 7.1T MRI 3 years postoperatively (in‐plane resolution: 125 μm × 125 μm). In refilled eyes, the capsule and the homogenous silicone polymer remained in close contact with no visible interface. The dimensions of the refilled lens were significantly smaller than those of the crystalline lens of the contralateral eye. CONCLUSIONS: High‐resolution MRI allows in vivo visualization and analysis of the spatial arrangement of the lens in rabbit eyes after lens refilling surgery and overcomes a number of major limitations in the quantitative evaluation of the lens shape. Further efforts are required to optimize the amount of polymer injected during lens refilling to achieve a predictable refractive outcome after lens refilling surgery. Financial Disclosure: Drs. Stachs, Langner, Sternberg, Martin, Schmitz, Hosten and Guthoff have no financial or proprietary interest in any material or method mentioned. Additional financial disclosure is found in the footnotes.

Drug-Induced Secondary Cataract Prevention: Experimental ex vivo and in vivo Results with Disulfiram, Methotrexate and Actinomycin D

Background/Aims: A clinical approach to prevent secondary cataract after lens implantation involves the intraocular application of pharmacological agents. The goals of our study were to develop an ex vivo model to test the drug effectiveness for lens epithelial cell ablation from the basal membrane and to verify the data in rabbit intraocular lens implantation experiments. Methods: Human capsular rhexis specimens were incubated with drugs and the residual cells were differentiated by use of the Live-Dead assay and quantified by staining with Hoechst dye. After phakoemulsification of rabbit eyes and before intraocular lens implantation, capsular bags were filled with drug-loaded hyaluronic acid for 5 min. Results: An ex vivo model was established which allows the testing of drugs on lens epithelial cell ablation. Drug treatment reduced the number of viable cells on the specimens drastically, ranging between 0.44 ± 0.53% (6.0 ± 7.3 cells/mm2) for disulfiram, 0.27 ± 0.50% (3.7 ± 6.9 cells/mm2) for methotrexate and 0.07 ± 0.19% (0.1 ± 0.27 cells/mm2) for actinomycin D. Rabbit eyes treated with a mixture of methotrexate/actinomycin D showed no posterior capsule opacification at 4 months and a low opacification 6 months postoperatively. Without drug treatment low opacification starts 6 weeks postoperatively. Conclusions: The drug screening in the described ex vivo model can help to reduce the number of preclinical studies for secondary cataract prevention. The successful ex vivo cell ablation by methotrexate/actinomycin D was confirmed by a delayed in vivo secondary cataract formation.

Development of a ciliary muscle-driven accommodating intraocular lens

PURPOSE: To develop a ciliary muscle–driven accommodating intraocular lens (IOL) that has a large and predictable range of variable power as a step toward spectacle independence. SETTING: Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands. METHODS: A concept IOL that has a rotating focus mechanism and a mechanical frame that can operate within the range of ciliary muscle contraction of a typical 60‐year‐old human eye was designed. Prototypes were made to test the IOLs mechanical performance in an enucleated pigs eye using a laboratory lens‐stretching device that mimics the action of the human ciliary muscle. Changes in focal length during stretching were measured by laser‐based ray tracing and a videocamera system. To rotate the 2 lenses in the IOL with variable optical power, a frame that allows the displacement and force of the ciliary muscle to be transferred by the capsular bag was designed. RESULTS: Ray tracing showed that the modulation transfer function (MTF) of the IOL in different accommodative states did not deviate to a great extent from the MTF of a monofocal IOL. During stretching experiments, the prototype IOL achieved 8.0 diopters of accommodation. CONCLUSIONS: Evaluation of an accommodating IOL that meets the requirements for a spectacle‐independent solution to presbyopia showed that the mechanical and optical designs must be further optimized to improve optical quality and functionality.

Prevention of capsule opacification after accommodating lens refilling: pilot study of strategies evaluated in a monkey model.

Purpose To test 2 strategies to prevent capsule opacification after accommodating lens refilling in a rhesus monkey model. Setting Animal laboratory and laboratory of European university medical centers. Design Experimental study. Methods Six rhesus monkeys had refilling of the lens capsular bag. In the first strategy, before it was filled with a silicone polymer, the capsular bag was treated with noncommercial sodium hyaluronate 1.0% containing cytotoxic substances. In the second strategy, the capsular bag was filled with clinically used sodium hyaluronate 1.0% (Healon) after treatment with actinomycin‐D. Slitlamp inspection was performed during a follow‐up of 40 to 50 weeks. After enucleation, magnetic resonance images were obtained and confocal fluorescence imaging was performed. Results Using the first strategy, capsule opacification developed in all eyes. Using the second strategy, 1 monkey did not develop capsule opacification after a 9‐month follow‐up. In a second monkey, the lens capsule remained clear for 3 months, after which the hyaluronate refill material was exchanged with a silicone polymer and capsule opacification developed. Combining these results with those in a previous study, the difference in opacification between silicone and sodium hyaluronate as refilling materials was statistically significant (P<.01). Conclusions That no capsular bag fibrosis occurred in the presence of hyaluronate suggests that the properties of hyaluronate are the reason that remaining lens epithelial cells do not develop into fibrotic cells. The choice of a suitable lens‐refilling material prevents the development of capsule opacification. Financial Disclosure Mr. Terwee was an employee of Abbott Medical Optics B.V. during the study period. No other author has a financial or proprietary interest in any material or method mentioned.

Contents Vol. 44, 2010

Anatomy, Pathology and Cell Biology A. Prescott, Dundee Biochemistry, Molecular Biology and Molecular Genetics J. Graw, Neuherberg Clinical and Epidemiological Research M. Kojima, Kahoku Clinical Retina P. Wiedemann, Leipzig Cornea and Ocular Surface C. Marfurt, Gary, Ind. Glaucoma H. Th ieme, Mainz Immunology and Microbiology U. Pleyer, Berlin Lens and Cataract S. Varma, Baltimore, Md. Miscellaneous U. Pleyer, Berlin Neuro-Ophthalmology and Vision Sciences P. Aydin, Ankara Ocular Oncology M. Jager, Leiden Physiology, Pharmacology and Toxicology A. Wegener, Bonn Retina and Retinal Cell Biology M. Boulton, Gainesville, Fla. P. Wiedemann, Leipzig Editorial Board