September 2007

 

CATARACT/ IOL

 

In vivo MRI … visualizing the haptics


by Susan A. Strenk Ph.D., Lawrence M. Strenk, Ph.D.

 

There is an increasing interest in the development of new intraocular lenses (IOLs) or other surgical techniques to restore accommodation in the presbyopic eye. An accurate understanding of the mechanism of accommodation in the human eye is necessary for the development of such lenses and surgical techniques. Different methods have been used by different research groups to evaluate the changes occurring in the anterior segment in response to accommodation. Some important examples are represented by induction of dynamic accommodation in anesthetized rhesus monkeys by stimulation of the Edinger-Westphal nucleus, or the mechanical stretching of isolated crystalline lenses used by Adrian Glasser, or the use of the anterior segment optical coherence tomography in albino patients used by George Baikoff.

Susan and Larry Strenk from MRI Research, Inc., in Cleveland are using an interesting approach. They have developed high-resolution anterior segment magnetic resonance imaging (MRI) techniques and instrumentation that permit complete visualization of the anterior segment. Their method provides visualization of the ciliary muscle and its geometric relationship to the crystalline lens in phakic eyes, or to the optic and haptic in pseudophakic eyes without obstructing vision and using binocular physiological accommodation. I have the pleasure to collaborate with them in their studies on Soemmering’s ring characterization with this method, which has the potential to greatly complement the information obtained in the studies we performed at the University of Utah and the Berlin Eye Research Institute using human eyes obtained postmortem. In this article, these researchers provide a summary of the current status of their research regarding accommodation and Soemmering’s ring characterization.

Liliana Werner, M.D., Ph.D.

Research Associate Professor, John A. Moran Eye Center, University of Utah Director Preclinical Research, Berlin Eye Research Institute, Berlin, Germany MRI and the Pseudophakic

 

Figure 1: Two contiguous slices through an Alcon AcrySof IOL in a 65 year old patient during resting accommodation showing the IOL haptics posterior to the ciliary muscle plane.

Figure 2: In vivo composite image showing a 49 year old (left) and a 25 year old; lens growth displaces the uveal tract anteriorly with age.

Figure 3: In vivo composite image showing both eyes of a 74 year old patient with monocular implantation of the Alcon AcrySof; the uveal tract returns to an anteropoterior position of relative youth with IOL implantation.

Figure 4: In vitro MR images showing postmortem changes in a 91 year old cadaver eye acquired at a) two and a half days post mortem with minimal swelling between anterior cortex and capsule and b) five days post mortem, note significant swelling between lens cortex and capsule.

Figure 5: Four examples of capsular contact with the iris secondary to SR development a) black dots are the cross-section of the loop haptics, SR development appears to have lead to optic malposition with capsular contact at the pupillary margin; b) and c) capsular contact at mid-iris; d) a 1 cm field-of-view image showing detail of capsular and mid-iris contact.

Figure 6: In vitro MR images of a hydrophilic acrylic plate haptic IOL showing the development of SR, which is hyperintense to surrounding aqueous and vitreous, in three orthogonal planes a) coronal image, SR appears donut shaped and of fairly uniform intensity; b) axial image, SR appears as an asymmetric dumbbell; c) sagittal image, SR is not seen in plane of the haptics.

Figure 7: In vitro MR images of a loop haptic IOL showing the development of SR, which is hyperintense to the aqueous and vitreous, in three orthogonal planes a) coronal image, SR appears as a diffuse donut shape; b) axial image, SR appears as an asymmetric dumbbell, haptics appear as black dots at periphery of SR, and the uvea is displaced on the right, possibly a result of SR developing posterior to the ciliary body resulting in capsular contact with the processes; c) sagittal image, SR appears as a fairly symmetric dumbbell.

Figure 8: In vitro MR images of an Alcon AcrySof showing the development of SR, which is hyperintense to the surrounding aqueous and vitreous, in three orthogonal planes: a) coronal image; b) axial image; c) sagittal image. Minimal SR is present especially in the plane of the haptics (b). Note the iris cyst visible in both the coronal and axial planes (a and b).

Figure 9: Gross photographs of rabbit (a), and human (b) pseudophakic postmortem eyes obtained from the posterior view of the anterior segment (Miyake-Apple view). Information obtained from these analyses can be complemented by MRI studies, which do not require previous sectioning of the eye. Source: Liliana Werner, MD, PhD.

MRI is a non-invasive, non-optical imaging modality that is not impeded by the iris; therefore, the entire intraocular or crystalline lens and its relationship to the anterior segment is readily visualized in vivo with unsurpassed soft tissue contrast and in multiple slices for any desired plane or planes. Thus MRI affords the unique opportunity to fully visualize the IOL (optic and haptics) and its relationship to the ciliary muscle for various accommodative states in vivo in the normal, intact human eye. Figure 1 shows two contiguous slices through a single-piece acrylic IOL (AcrySof SA60AT, Alcon, Fort Worth, Texas) in a 65 year-old patient during resting accommodation. Note that the IOL haptics are somewhat posterior to the ciliary muscle; we frequently observed this geometry. Recent ultrasound biomicroscopy studies similarly suggest that IOLs are often located posterior to the ciliary body.1 Pseudo-accommodation is unlikely to occur when the haptics are posterior to the ciliary muscle and, in fact, we noted no anterior movement of the optic or haptics with accommodative ciliary muscle contraction in this subject.

Lens growth and presbyopia development

Our in vivo MRI studies of the phakic human eye have provided statistically significant support for the Helmholtz theory of accommodation (although we observe contributions from the iris and sclera).2-4 Our findings have also led to a new theory of presbyopia development.3 Given that the crystalline lens grows throughout life and that accommodative loss begins in childhood, lens growth has long been suspected of causing presbyopia.5 We find lens growth, with its concomitant increase in thickness, correlates with anterior and inward uveal tract displacement (Figure 2) and that the diameter of the ciliary muscle as well as circumlental space decrease significantly with age.2,4 It is thought that forces applied by the lens to the iris and iris root, coupled with the constraints of scleral curvature, displace the ciliary muscle both anteriorly and inward with age, reducing circumlental space, zonular tension, and, consequently, lens response. This “modified geometric theory” owes much to the original Geometric Theory, put forth nearly 20 years ago, which held that lens growth changed the geometric relationship between the ciliary muscle and lens and caused increases in zonular tension until the ciliary muscle was unable to move; however, MRI studies of both phakic and pseudophakic patients reveal that accommodative ciliary muscle contraction is undiminished either by age or by IOL implantation rendering the original theory unsustainable.2,4,5 Strategies for the surgical correction of presbyopia can thus rely upon a functioning ciliary muscle with approximately 0.64 mm of contraction. Furthermore, IOL implantation returns the uveal tract to a relatively youthful anteroposterior location (see Figure 3). Unfortunately, the ciliary muscle is not restored to its youthful diameter, probably due to an age-dependent increase in connective tissue.4,6,7 Nonetheless, postoperative capsular contraction likely restores some zonular tension. Species differences: implications for the surgical correction of presbyopia While the rhesus monkey has been used as an animal model for human accommodation, numerous species differences in the lens, ciliary muscle and other accommodative structures and how these structures change with age have long been known to exist and our MRI studies have revealed additional differences.3 For example, unlike humans, ciliary muscle movement is diminished with age in the rhesus.8 Another striking difference is that, while the rhesus ciliary muscle displaces posteriorly with age, we find that the human ciliary muscle does the opposite; it moves anteriorly.6 Additionally, while the rhesus ciliary muscle moves both upward and inward with accommodation, the human ciliary muscle only moves inward in the phakic eye. This lack of anterior ciliary muscle movement with accommodation in humans has also been demonstrated by OCT of phakic albino subjects (the reduced iris pigment allows OCT to image behind the iris) and certainly has implications for accommodating IOL designs.9 Reports that the human ciliary muscle develops more connective tissue and in different locations than the rhesus, indicate that it is subject to different forces.6-8 The biometric differences in anterior segment geometry of the human and rhesus need to be fully characterized in vivo since different geometric relationships between the ciliary muscle and lens in each species will lead to different accommodative forces being applied to any implanted IOL or refilled capsule and will thus have implications in the development of strategies for the surgical correction of presbyopia. In vitro MRI … lens mechanical changes and presbyopia development In vitro MR imaging of cadaver eyes cannot provide data on the effect of physiological accommodation on either an IOL or the crystalline lens; nonetheless, it permits higher resolution imaging of the anterior segment and a much-needed calibration between in vivo data and human cadaver biometry. While some studies of the isolated lens have implicated mechanical changes in lens material as a causal factor in presbyopia development, it has frequently been noted that these studies fail to account for the early onset of accommodative loss and suffer from significant post mortem tissue changes, the application of non-physiological forces, and inappropriate statistical treatment of the data; when adequate statistical analysis is performed, no change in lens mechanical properties is found until after age 70.10-15 MRI reveals that post mortem water uptake between the human lens cortex and capsule occurs after approximately 48 hours (see Figure 4); similarly it has recently been reported that the bovine lens begins to take up water starting 30 hours post mortem.12 This water uptake will affect the size and shape of the lens as well as its mechanical and optical properties; thus, extreme caution is needed when interpreting in vitro lens studies. Additionally, any mechanical changes in the lens that may occur with age could be a result, not a cause, of presbyopia; it has long been theorized that a certain amount of accommodative lens movement is needed to prevent biochemical degradation of the lens material.5 If so, depending upon when implemented, strategies for the surgical correction of presbyopia that leave the crystalline lens in place could potentially arrest/reverse this biochemical degradation.

IOL sizing

Our preliminary MRI studies comparing in vivo biometry to that of phakic cadaver globes utilize globes less than 48 hours post mortem and thus free of significant water uptake. Nonetheless, we find that cadaver lens biometry is quite different than in vivo lens biometry. One difference relevant to IOL design is that the diameter of the in situ cadaver lens is approximately 4% greater than the in vivo lens, likely due to the affect of the loss of intraocular pressure on the shape of the crystalline lens. Consequently, reliance on cadaver lens biometry, without appropriate calibration, could lead to haptic over sizing and ultimately IOL malposition. Recent ultrasound biomicroscopy studies have also raised concerns that IOLs may be oversized.1

Characterizing Soemmering’s ring

Soemmering’s ring (SR) occurs, to some degree, after virtually every extracapsular cataract surgey.16 It is a precursor to posterior capsule opacification (PCO) and even when it does not advance to PCO is potentially capable of causing complications such as pupillary block glaucoma and iris and sulcus irritation.17-20 Our preliminary data support these observations and suggest that capsular contact with the iris may occur secondary to SR development (see Figure 5). This may have implications for glaucoma either through direct anterior mechanical displacement of the uvea and concomitant narrowing of the angle or through abrasion and migration of the pigment epithelium to the trabecular meshwork, especially when contact occurs with the mid-iris thus exposing a greater surface area to abrasion. Any pressure lowering effects of cataract surgery in glaucoma patients appear to be lost within one to two years of surgery, which corresponds approximately to the timeframe of SR development. The formation of SR depends upon residual/regenerative cortex and lens epithelial cells and the rabbit model can rapidly reveal an “Achilles’ heel” in the barrier effect provided by new IOL designs.16, 21 Soemmering’s ring takes much longer to develop in humans and, historically, adverse effects of new IOL designs have often remained undetected for years after their introduction. While MRI cannot provide histological information on SR or PCO, it has the unique ability to characterize SR in situ in the undisturbed cadaver globe and to correlate it with anterior segment biometry and IOL malposition in multiple planes (Figures 6-8). A positive correlation has been found between PCO and IOL tilt and decentration and our initial cadaver studies suggest that a correlation between the development of SR and IOL malposition may also exist.22,23 Ultimately MRI may prove useful in identifying SR in vivo thus allowing additional feedback to be obtained on newly introduced IOL designs. In summary, while currently MRI is not practical for pre- or postoperative clinical assessment, it is a valuable tool in the study of the effects of IOL implantation on the accommodative structures as well as the effects of accommodative effort on the position of the IOL optic and haptics. This research tool is also providing new insights into the mechanisms of accommodation and presbyopia, the determination of IOL sizing, and the development of Soemmering’s ring.

References

1 McGrath, D. New research carries important implications for the future design of standard and accommodating IOLs. ESCRS Eurotimes, 2007 (January):4.

2 Strenk, S.A., Semmlow, J.L., Strenk, L.M., Munoz, P., Gronlund-Jacob, J., DeMarco, J.K. Age-related changes in human ciliary muscle and lens: a magnetic resonance imaging study. Invest Ophthalmol Vis Sci, 1999;40 (6):1162-1169.

3 Strenk, S.A., Strenk, L.M., Koretz, J.F. The mechanism of presbyopia. Prog Retin Eye Res, 2005;24 (3):379-393.

4 Strenk, S.A., Strenk, L.M., Guo, S. Magnetic resonance imaging of aging, accommodating, phakic, and pseudophakic ciliary muscle diameters. J Cataract Refract Surg, 2006;32 (11):1792-1798.

5 Koretz, J.F., Handelman, G.H. How the human eye focuses. Sci Am, 1988;259 (1):92-99.

6 Tamm, S., Tamm, E., Rohen, J.W. Age-related changes of the human ciliary muscle. A quantitative morphometric study. Mech Ageing Dev, 1992;62 (2):209-221.

7 Pardue, M.T., Sivak, J.G. Age-related changes in human ciliary muscle. Optom Vis Sci, 2000;77 (4):204-210.

8 Lutjen-Drecoll, E., Tamm, E., Kaufman, P.L. Age changes in rhesus monkey ciliary muscle: light and electron microscopy. Exp Eye Res, 1988;47 (6):885-899.

9 Baikoff, G., Lutun, E., Wei, J., Ferraz, C. Anterior chamber optical coherence tomography study of human natural accommodation in a 19-year-old albino. J Cataract Refract Surg, 2004;30 (3):696-701.

10 Glasser, A., Campbell, M.C. Presbyopia and the optical changes in the human crystalline lens with age. Vision Res, 1998;38 (2):209-229.

11 Glasser, A., Campbell, M.C. On the potential causes of presbyopia (reply). Vision Res, 1999;39:1267-1272.

12 Augusteyn, R.C., Cake, M.A. Post-mortem water uptake by sheep lenses left in situ. Mol Vis, 2005;11:749-751.

13 Augusteyn, R.C., Rosen, A.M., Borja, D., Ziebarth, N.M., Parel, J.M. Biometry of primate lenses during immersion in preservation media. Mol Vis, 2006;12:740-747.

14 Deussen, A., Pau, H. Regional water content of clear and cataractous human lenses. Ophthalmic Res, 1989;21 (5):374-380.

15 Weale, R.A. On potential causes of presbyopia. Vision Res, 1999;39 (7):1263-1272.

16 Pandey, S.K., Apple, D.J., Werner, L., Maloof, A.J., Milverton, E.J. Posterior capsule opacification: a review of the aetiopathogenesis, experimental and clinical studies and factors for prevention. Indian J Ophthalmol, 2004;52 (2):99-112.

17 Kobayashi, H., Hirose, M., Kobayashi, K. Ultrasound biomicroscopic analysis of pseudophakic pupillary block glaucoma induced by Soemmering’s ring. Br J Ophthalmol, 2000;84 (10):1142-1146.

18 LeBoyer, R.M., Werner, L., Snyder, M.E., Mamalis, N., Riemann, C.D., Augsberger, J.J. Acute haptic-induced ciliary sulcus irritation associated with single-piece AcrySof intraocular lenses. J Cataract Refract Surg, 2005;31 (7):1421-1427.

19 Micheli, T., Cheung, L.M., Sharma, S., Assaad, N.N., Guzowski, M., Francis, I.C., Norman, J., Coroneo, M.T. Acute haptic-induced pigmentary glaucoma with an AcrySof intraocular lens. J Cataract Refract Surg, 2002;28 (10):1869-1872.

20 Wintle, R., Austin, M. Pigment dispersion with elevated intraocular pressure after AcrySof intraocular lens implantation in the ciliary sulcus. J Cataract Refract Surg, 2001;27 (4):642-644.

21 Werner, L., Mamalis, N., Pandey, S.K., Izak, A.M., Nilson, C.D., Davis, B.L., Weight, C., Apple, D.J. Posterior capsule opacification in rabbit eyes implanted with hydrophilic acrylic intraocular lenses with enhanced square edge. J Cataract Refract Surg, 2004;30 (11):2403-2409.

22 Schmidbauer, J.M., Vargas, L.G., Apple, D.J., Escobar-Gomez, M., Izak, A., Arthur, S.N., Golescu, A., Peng, Q. Evaluation of neodymium:yttrium-aluminum-garnet capsulotomies in eyes implanted with AcrySof intraocular lenses. Ophthalmology, 2002;109 (8):1421-1426.

23 Tetz, M.R., O’Morchoe, D.J., Gwin, T.D., Wilbrandt, T.H., Solomon, K.D., Hansen, S.O., Apple, D.J. Posterior capsular opacification and intraocular lens decentration. Part II: Experimental findings on a prototype circular intraocular lens design. J Cataract Refract Surg, 1988;14 (6):614-623.

In vivo MRI … visualizing the haptics In vivo MRI … visualizing the haptics
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