Does a sharp edge compress the posterior capsule in vivo? (2005)

Reply: I appreciate Dr. Nishi's interest in our paper. Before answering his questions, I want to mention important points about the natural events after cataract surgery. Posterior capsule bend along the IOL optic is clinically and experimentally formed several weeks or months after surgery. What induces the capsule bend is an important question. The lens capsule has no power to move. There must be another force that deforms the posterior capsule along the optic. In general, a wound-healing reaction exerts force, affecting the lens capsule and deforming the capsule. In particular, anterior–posterior capsule adhesion and capsule contraction are significantly associated with capsule deformation in wound-healing reactions. Although the posterior capsule is bent along the optic, there must be anterior movement of the posterior capsule and contraction of the capsule (reducing capsular bag volume) because the posterior capsule is a smooth membrane with a configuration closely resembling a sphere and the volume of the capsular bag is greater than that of the optic. Anterior–posterior capsule adhesion induces anterior movement of the posterior capsule and is always accompanied by a degree of capsule contraction. When the posterior capsule comes in contact with the optic edge according to anterior movement of the posterior capsule, contact pressure is generated between the optic edge and the posterior capsule. For the posterior capsule to adhere to both the posterior surface and side wall of the optic, it must be deformed (ie, not in its original configuration). The deformation at the posterior optic edge is usually stretching of the capsule. Contact pressure increases in accordance with the degree of the capsule stretch during capsule deformation along the optic configuration. In almost all cases, a capsule bend along the optic edge means there is contact pressure at the optic edge. When an IOL with a sharp or round edge is implanted, it induces a sharp or round capsule bend, respectively, along the optic edge. The degree of capsule stretch at the optic edge is greater with a sharp capsule bend than a round capsule bend. Thus, the contact pressure at the optic edge is greater with a sharp capsule bend because the pressure correlates with the degree of capsule deformation. I would like to answer Dr. Nishi's questions corresponding to their numbering. In some cases, contact pressure at the optic edge before the formation of capsule adhesion and contraction might be slight. The configurations of the capsular bag and IOL are more important than the volumes and surface areas in generating pressure between an IOL and the capsule without capsule adhesion and contraction. If an IOL has a round optic and 2 open loops, the diameter of the capsular bag, total length of the IOL, and total height of the IOL (from the tip of the loop to the lowest point of the optic) are major factors in the exertion of force between the capsule and IOL. When the total length of the IOL is appropriately larger than the diameter of the capsular bag and the haptics have an appropriate angle, the posterior capsule contacts the optic edge and is stretched against the IOL by the action of the haptics and zonules. Boyce and coauthors1 mathematically calculated the contact pressure between the optic and the posterior capsule and concluded that IOLs with a square-edged optic profile exert more pressure on the posterior capsule than IOLs with round-edged optics.1 It is rare to see a slack posterior capsule that is apart from the IOL several months after surgery. In such cases, there is no contact pressure between the optic and posterior capsule and no capsule bend along the optic edge. Accordingly, such cases are not in the range of this discussion. In many cases, when there is no contact between the posterior capsule and the central posterior surface of the optic, the posterior capsule makes contact with the optic edge. In such cases, a mild capsule bend and mild contact pressure must exist at the optic edge. In Figure 1, A and B, the stretched posterior capsule is in contact with the posterior surface of the optic, bends at the posterior optic edge, climbs along the side wall of the optic, and makes the second bend at the capsule adhesion. Then, the posterior capsule loses its stretched profile and goes toward the equator in a wave pattern. The stretched, deformed capsule indicates the presence of horizontal tension toward the periphery in the central posterior capsule in contact with the posterior optic surface and vertical tension toward the anterior in the posterior capsule in contact with the side wall of the optic. Extracellular matrices, including collagens, adhere the anterior and posterior capsules and contract during spatial organization of the matrix. Contraction of the adhesive matrices induces the force producing capsule contraction. Because this contraction occurs around the optic, it pulls and stretches the central posterior capsule toward the periphery and anteriorly along the posterior part of the optic. It also pulls the peripheral posterior capsule toward the optic edge, resulting in the formation of capsule folds. In eyes with a square-edged IOL, there is enough contact pressure to inhibit cell migration at the optic edge, as shown in Figure 1, A and B.When the capsular bag is small or filled with something, such as remaining or regenerated lens fiber cells, there are fewer capsule folds at the peripheral posterior capsule. There are also fewer peripheral capsule folds and central posterior capsule tension in cases of weak capsule adhesion and contraction, and peripheral cells can migrate through the adhesive matrix onto the central posterior capsule, as seen in Figure 1, C. In other words, when the optic is tightly packed in the lens capsule, capsule tension is high and cell migration is inhibited. The reverse is also true, allowing cells to migrate.Figure 2, A, is not compatible with capsule contraction syndrome. I speculate that the figure demonstrates liquefied after-cataract (late-postoperative capsule block syndrome). Because I have never clinically observed this eye, I am not sure; however, I think the case shown has abundant extracellular matrices and anterior–posterior capsule adhesion around the optic and that the cataract surgery was performed a long time ago. According to the time after surgery, extracellular matrices lose their flexibility, resulting in loss of flexibility at the capsule adhered to the matrices. In contrast, the area of the capsule not adhering to the matrices does not loose flexibility. I think the Nd:YAG capsulotomy was performed at the central posterior capsule, which had some flexibility, and the disrupted capsule became slack after the capsulotomy. Although there would be no contact pressure between the central posterior capsule and the optic in this case, that does not mean there was no contact pressure at the posterior capsule in contact with the optic edge because contact pressure can be different at any part of the posterior capsule. It seems easy to understand the difference in contact pressures at the rigid capsule in contact with the optic edge and at the central flexible capsule separating from the optic. Dr. Nishi mentioned that capsule tension created by the haptic would disturb capsule bending or compression pressure because it would work against pulling up the posterior capsule along the optic edge. I think the reverse is true. Contact inhibition of cell division should not be confused with contact inhibition of cell movement. Cell division and cell movement are different and independent events. Contact inhibition of cell division means density-dependent inhibition of cell division. Cell proliferation ceases when cell density is high. If a sharp capsule bend induces contact inhibition of cell division, how does it induce high cell density? On the other hand, contact inhibition of cell movement means the immediate paralysis of the leading edge of each cell and the following change in direction of cell movement after cell collision. How does a sharp capsule bend relate to contact inhibition of cell movement? I think, perhaps, that Dr. Nishi refers to inhibition of cell migration at a sharp optic edge as “contact inhibition” because he believes cell contact with a sharp capsule bend ceases migration. Even if this is true, although it is unlikely, the phenomenon cannot be called contact inhibition because of the reasons mentioned above. Even when a sharp capsule bend blocks cell migration, other term should be to explain the mechanism. I cannot understand the point Dr. Nishi is making with respect to Figure 2, B. Where is the sharp capsule bend? When cells migrate, they extend lamellipodia toward the migrating direction and make new adhesive contacts; they then break the adhesive contacts, locating at the area opposite the migrating direction. They move their body to the migrating direction according to contraction of their body. They do not have to bend their body rectangularly while climbing the rectangular wall from the bottom of the well. They simply extend the leading edge on the rectangular wall and make adhesive contact. Bhermi and coauthors2 clearly demonstrated that, under adequate conditions, LECs can migrate over a sharp rectangular edge of a well and can climb the rectangular wall from the bottom. Next, I would like to answer Dr. Nishi's other questions. Although we might not be able to measure real contact pressure between the optic edge and the capsule, we can speculate the pressure theoretically or calculate it mathematically. As mentioned above, Boyce and coauthors1 mathematically calculated the contact pressure between the optic and posterior capsule and concluded that IOLs with a square-edged optic exert higher pressure on the posterior capsule than IOLs with a round-edged optic. In an earlier study,3 Dr. Fujiwara and I made a straight groove on a plastic sheet using a knife and then bent the sheet at the reverse side of the groove, easily making a sharp bend. Although we did not demonstrate the sharp capsule bend in our paper, Bhermi and coauthors2 clearly showed the sharp bend at the well corner and demonstrated that LECs can migrate over a sharp rectangular edge of collagen-coated poly(methyl methacrylate) well. We also demonstrated that cells migrate over the sharp bend of the posterior capsule. I do not understand what the “thickness of each IOL” means. Is that the thickness of the optic at the center or the thickness of the ridge and edge? Finally, Dr. Nishi's comments and questions include many misunderstandings and seem to be incorrect based on scientific theories and findings in cell biology and physics. I believe the conclusion in our study is adequate. Toshiyuki Nagamoto MD, PhD