The concept of retrograde trans-synaptic degeneration leading to isolated INL cystoid changes is plausible and a potentially interesting feature of optic neuropathies, including optic neuritis, optic atrophy, and compressive optic neuropathies. In contrast to the report by Green,
7 in fact INL cystoid changes have been seen in glaucomatous optic neuropathy, and have recently been formally reported.
12 However, many glaucoma patients (as well as many otherwise healthy patients) also have had cataract extraction, and are on prostaglandin analogs for IOP control. These factors are also both well-known causes of CME, which commonly involves the INL.
8 Our report of delayed-onset INL cystic changes
10 was unique to previously observed INL cystoid changes for several reasons. First, the cystoid spaces were always absent in the reported cases before EMM removal and internal limiting membrane (ILM) peeling. The findings appeared at least several weeks after surgery, and displayed no angiographic leakage. Since that report, we have demonstrated no improvement in these cystoid spaces with topical or periocular glucocorticoids (six cases), topical carbonic anhydrase inhibitors (five cases), and topical nonsteroidals (eight cases), and have observed only mild worsening in all cases, which are distinct features from typical CME. As illustrated in the
Figure, these cystoid changes are focal (not circumfoveal) and often correspond to areas deep to obvious nerve fiber layer (NFL) defects from forceps grasp sites. Interestingly, however, even with the most delicate techniques and ILM forceps, many obvious NFL defects are seen postoperatively, with little, if any, visual consequence. Delayed-onset INL cystoid changes, however, are exceedingly rare (roughly 1%), indicating that additional factors besides mechanical trauma are important in the development of these findings. We have hypothesized that the appearance results from Müller cell dropout, which may occur from physical trauma (ILM peeling or NFL grasp sites). The fact that INL cystoid changes are only rarely seen may result from a critical stretch or mechanical trauma threshold for which cell loss occurs in a subset of epimacular membranes, and therefore may represent the severity of the underlying EMM and the quantity of shear force required for membrane removal. This is consistent with recent experimental evidence that Müller cells are particularly pliable and respond with a spectrum of intracellular responses to various levels of mechanical stretch.
13 Müller cell trauma and dropout would likely result in loss of additional INL cell types, which is consistent with our observation that the INL cysts tend to enlarge slightly over time, but do not appear to migrate laterally.