The dead bag syndrome

Diagnosis is not the end, but the beginning of practice. —Martin H. Fischer The rate of late postoperative in-the-bag intraocular lens (IOL) dislocation has been reportedly increasing, and among the known predisposing conditions are pseudoexfoliation, uveitis, myopia, pars plana vitrectomy, and other conditions associated with progressive zonular weakening.1 However, since the early 2000s, there have been presentations and discussions at different meetings and online forums about IOL dislocation cases where the capsular bag itself had apparently become diaphanous, floppy, and unable to support the IOL within it. The cases seemed to share the common feature of a very clear bag many years postoperatively, and Sam Masket, who first observed the condition, coined the term dead bag syndrome to refer to them. In our laboratory at the John A. Moran Eye Center, we had looked forward to collecting a significant amount of cases and specimens to perform an initial formal study evaluating this condition. We recently had this opportunity, through collaboration with Masket and 3 other surgeons recognizing similar cases, Drs. Jason Jones, Nicole Fram, and Gregory Ogawa, culminating in the first peer-reviewed study, to our knowledge, on the dead bag syndrome, published in the February issue by Culp et al.2 A total of 10 cases were included, with a mean time between implantation and explantation (when performed) of 10.6 ± 5.6 years. It is noteworthy that no signs of zonular instability were reported during the implantation surgeries, which were all uneventful. In 7 cases, the IOLs and capsular bags were explanted, and all 7 capsular bags were analyzed through detailed histopathology, as well as 5 of the 7 explanted IOLs. At presentation, there was subluxation of the IOL inside of the floppy bag, sometimes through a peripheral defect, while the capsular bag itself was still centered. In other cases, there was in-the-bag IOL dislocation. The main feature of histopathology was capsular splitting or delamination. Lens epithelial cells (LECs) were rarely seen or were completely absent from the inner surface of the capsule. Only 1 capsular bag specimen had mild amounts of anterior fibrous metaplasia, and another capsular bag contained a small amount of cortical material on microscopic examination. The explanted IOLs were either 3-piece silicone or single-piece hydrophobic acrylic IOLs and were unremarkable under light microscopy aside from mild pigmentary dispersion on their surfaces.2 In the same study, 3 other cases of possible dead bag syndrome were also included.2 In one of them, only the IOL was explanted; inferior dislocation of the single-piece IOL into the vitreous cavity occurred through a peripheral/posterior capsular defect, while the residual capsular bag still appeared to have appropriate zonular support. In this case, sulcus fixation of a 3-piece hydrophobic acrylic lens with posterior optic capture was performed. In the other 2 cases, explantation of the IOL or the capsular bag was not found necessary although, in one of them, nasal zonulysis has been observed more recently. Histopathological findings of the dead bag syndrome capsules were compared with those of capsules from 40 cases of in-the-bag IOL dislocation, including 26 cases with evident pseudoexfoliation material.2,3 LECs and Soemmerring's ring formation were observed in all cases; capsulorhexis phimosis was also a relatively common finding, while capsular splitting/delamination was only found in 1 specimen. A review of the literature indicates there is also capsular splitting/delamination in true exfoliation syndrome.4 However, in this condition, which can be associated with chronic exposure to intense heat or infrared radiation, there is usually a thin membrane of delaminated capsule on the anterior surface of the crystalline lens before cataract surgery. Specific differences with the abovementioned conditions show dead bag syndrome to be a distinct entity. The exact etiology of dead bag syndrome is as of yet unknown, but we hypothesize that late postoperative zonular failure is related to capsule splitting/delamination occurring at the level of zonular attachments. This syndrome does not have any association with a particular IOL design or material. When looking at the results of the study by Culp et al., especially regarding the scarcity of LECs in the capsules, many surgeons are naturally asking the question whether capsular polishing has any relationship with this syndrome.2 It is, indeed, described that cortical lens fibers and LECs continue to deposit extracellular matrix and lens capsule components at their basal ends, which contributes to the thickening of the capsule throughout life and maintaining its integrity.5 There has been a recent emphasis on polishing techniques to prevent capsular bag fibrosis and opacification, especially in association with premium IOLs.6–9 However, even extensive polishing cannot completely remove all LECs, and polishing is usually not performed at the capsular bag equator, as this region is not readily visible. Therefore, to date, there is no established association between capsular polishing and this condition. Masket has also observed cases of white, intumescent cataracts that evolved into dead bag syndrome, suggesting that there may be a role of oncotic pressure within the capsular bag in killing LECs. However, many dead bag cases are not related to this type of cataract, and other factors are likely involved in its origin. There have been numerous informal discussions about the dead bag syndrome in sites such as the EyeConnect Listserv (ASCRS) and the Kera-net (official online resource of the Cornea Society). Surgeons who have also been recognizing this syndrome, such as Steven Safran, among others described many apparent dead bag cases that were not associated with extensive polishing and cases where the capsule was floppy and delicate but still exhibited a certain amount of proliferative material within it, including abnormal gel-like Soemmerring's ring formation. It is possible that the findings described in the study by Culp et al. may represent the severe end of a spectrum. In discussions with researchers focused on the crystalline lens, such as Melinda Duncan (email communication, January 2022), it becomes evident there are still some unknowns in the relationship between LECs and the capsule, especially postcataract surgery. Although, as noted earlier, LECs are important for the formation of the capsule, this structure represents an anchor point for the basal surfaces of epithelial and fiber cells, in addition to providing necessary signals for proper lens cell proliferation, migration, and differentiation.10 In the dead bag syndrome, another possibility is that the initial problem is in the capsule itself, which would initiate a cycle of LEC damage, with further damage to the capsule. There are many unanswered questions not only about the etiology of this syndrome but also in its manifestations. It is therefore fitting that management is advised on a case-by-case basis, depending on presentation and status of the zonular support. The study by Culp et al. was meant to represent an initial formal assessment of dead bag syndrome, raising awareness of this condition and establishing a basis for further discussions and much needed additional formal studies to ascertain its exact etiology. As such, we certainly hope it accomplished its goal.