Is Nonarteritic Ischemic Optic Neuropathy Due to Choroidal Compression of the Prelaminar Neurovascular Compartment of the Optic Nerve Head?

Editorial Is Nonarteritic Ischemic Optic Neuropathy Due to Choroidal Compression of the Prelaminar Neurovascular Compartment of the Optic Nerve Head? Christopher A. Girkin, MD, MSPH T he advent of spectral domain and swept-source optical coherence tomography (SD-OCT and SSOCT, respectively) along with enhanced depth imaging (EDI), postprocessing shadow removal, and light attenuation compensation algorithms have improved the visualization of the deep structures in the optic nerve head including the anterior surface structure of the lamina cribrosa and sclera (1). These techniques have afforded the opportunity to visualize and quantify the in vivo morphology of the underlying load-bearing connective tissues of the optic nerve head (i.e., the peripapillary sclera and lamina cribrosa), the overlying neurovascular tissues lying within the rim and cup, and the surrounding peripapillary choroid. The ability to visualize these components of the optic nerve head provide an unprecedented opportunity to explore the differential effects of aging and disease on these regions of the optic nerve in the living eye. This is fueling the development of new biomarkers for glaucoma and, possibly, other optic neuropathies that have mechanistic relevance and may further serve to differentiate different types of optic neuropathies based on the differential effects within these tissues. The article in this issue of the Journal of Neuro-ophthalmology by Pérez-Sarriegui et al (2) is the first report of choroidal thickness in the macula and surrounding the optic nerve head in nonarteritic anterior ischemic optic neuropathy (NAION) using SS-OCT. Their findings are additive to a body of literature exploring the in vivo structural findings provided by SD-OCT and SS-OCT in NAION. Previous studies have suggested that the classic interpretation of the "disc-at-risk" may be inaccurate, namely that the optic nerve head may be "small" or "crowded" (3). Several SD-OCT studies have now shown that Bruch membrane opening (BMO), the anterior opening of the neural canal, is actually not smaller in patients with NAION than in age-matched controls (4-6). SD-OCT also has demonstrated that ophthalmoscopic identification by the clinician of the optic disc boundary often does not correspond to the location of BMO or the anterior scleral canal opening (7). This adds to the variability in the estimation of optic disc size, a critical factor in the diagnosis of glaucoma, and may explain these discrepancies seen with imaging based disc area. Interestingly, Pérez-Sarriegui et al found that both the involved and fellow eyes of patients with NAION had much thicker peripapillary choroid than control eyes. Their study confirms results from our group (8) and Fard et al (9) in finding a bilaterally thicker choroid in patients with NAION. By contrast, 1 previous study found a thinner peripapillary choroid in eyes with NAION and their fellow eyes when compared with control eyes (10). That study quantified choroidal thickness using only single horizontal and vertical b-scans centered on the optic nerve head with EDI SD-OCT and not a 3dimensional quantification of the entire surface. Moreover, there was no compensation algorithm used, which may have limited the visualization of the anterior sclera. Most importantly, the control group was significantly more hyperopic than the patients studied and this may have accounted for a thicker choroid found in the control group. Indeed, the control group had a choroidal thickness of over 180 mm, much thicker than that reported in any of the other studies. Table E5 found in the article by Pérez-Sarriegui et al, provides a helpful summary of this literature. Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. Supported by Eyesight Foundation of Alabama (Birmingham, AL); and Research to Prevent Blindness Inc (New York, NY). The author reports no conflicts of interest. Address correspondence to Christopher A. Girkin, MD, MSPH, Department of Ophthalmology, University of Alabama at Birmingham, Callahan Eye Hospital, 700 South 18th Street, Birmingham, AL 35223; E-mail: [e-mail] Girkin: J Neuro-Ophthalmol 2018; 38: 1-3 1 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Editorial It is important to note how large the mean differences in choroidal thickness are in these 3 studies with similar methodology. They show that peripapillary choroidal thickness in eyes with NAION range from 121% to 143% of the normal mean thickness. In our study, there was almost complete separation between NAION and control groups, something rarely seen in structural biology studies of the optic nerve. It is interesting that the thicker choroid was seen in both the affected and unaffected eyes in patients with NAION. This suggests that a thick choroid is a morphometric risk factor for the development of NAION and not a result of NAION. Perhaps, the appearance of a "crowded" disc is due to the increase in the vertical height of the prelaminar neural tissue caused by a very thick peripapillary choroid. Understanding the exact vasculature involved in NAION is central to the debate regarding pathophysiology. Fluorescein angiographic studies in NAION have demonstrated delayed filling in the prelaminar optic disc, suggesting that paraoptic branches of the short posterior ciliary arteries (SPCA) are involved in the infarction (11,12). In addition, limited histologic studies of human eyes with NAION show that the infarction is in the retrolaminar optic nerve extending into the laminar and prelaminar region (13). A compartment-like syndrome has also been proposed in the pathophysiology of NAION, presumably from crowding of the optic nerve fibers (2). In our previous study, we proposed a link between this compartment syndrome and the thick choroid by suggesting an alternate hypothesis for pathogenesis of NAION (8). We speculated that the prelaminar neural tissues became compressed by a circumferential thickened choroid (Fig. 1). As choroidal thickness varies with fluid volume and body position, the level of compressive strain within the prelaminar space may reach a magnitude that could exceed capillary perfusion pressure. The infarction and resulting edema would further increase prelaminar compressive strain, creating a feedback mechanism that would enlarge the region of ischemia extending to the laminar and retrolaminar space. Aging effects within the prelaminar vasculature might also increase the vulnerability of the prelaminar capillaries to this choroidal-based mechanism, which would explain the associations of NAION with age and vascular disease. Moreover, the observations that NAION occurs more commonly at night (14) and with the use of erectile dysfunction medications (15) are plausible with the hypothesis given that the supine position and these drugs are associated with the thickening of the choroid (16,17). Although the mean choroidal thicknesses in all these studies were not significantly different between the affected and unaffected eyes in patients with NAION, the mean choroidal thickness in the eyes with NAION was thinner than the contralateral unaffected eye. Given the relatively small sample size of these studies and that mean differences were directionally similar, it may be that there is some thinning of the thickened choroid after NAION. In theory, this might provide a rationale as to why NAION is seldom recurrent. However, larger studies are needed to assess this possibility. Additional evidence for a prelaminar compartment syndrome comes from a recent study using SD-OCT to define the acute effects of NAION on the deep tissues of the optic nerve head. Rebolleda et al (18) found that in acute NAION, BMO in the involved eyes was significantly larger than in the contralateral uninvolved eyes. The anterior surface of the lamina cribrosa also was displaced posteriorly compared with that of the uninvolved eye. When reimaged 6 months later, when the optic disc edema had resolved, the authors found that these changes in BMO size had resolved and the lamina cribrosal surface was slightly shallower in the affected eye. These findings support an acute expansion of the prelaminar neurovascular tissue space resulting from ischemia and edema within this compartment. FIG. 1. Conceptual images illustrating the hypothesis of compartment syndrome due to alterations in choroidal volume in an eye with thick peripapillary choroid. A. Thick peripapillary choroid in an eye predisposed to nonarteritic ischemic optic neuropathy. B. Expansion of the peripapillary choroid in this eye in response to positional or volume changes causing a compartment syndrome in the laminar, prelaminar, and retrolaminar optic nerve with resultant ischemia and increasing edema. Used with permission from (8). 2 Girkin: J Neuro-Ophthalmol 2018; 38: 1-3 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Editorial Alternatively, because the peripapillary choroid is supplied by the same vascular bed as the laminar regions of the optic nerve head, the thick overlying choroid may represent an anatomical variation in the distribution of the vascular supply of the paraoptic branches of the SPCA. This could be a marker for a vulnerability in this vascular network or perhaps represent a "steal" phenomenon with excessive blood flow to the thickened peripapillary choroid. Unfortunately, current OCT approaches can only reveal the structural anatomy and no current approach can accurately determine the vascular flow in these regions. Regardless of the pathophysiology, if a thick choroid is causally associated with NAION, it could provide a potential new SD-OCT biomarker to estimate the risk to the fellow eye in patients with unilateral NAION. Moreover, it also might provide an avenue for the treatment to reduce the risk of NAION in the unaffected eye by "decompressing" the peripapillary choroid. Therapeutic approaches could be aimed at thinning the choroid around the optic nerve head using laser-based methods or by thinning the peripapillary sclera. It is critical to point out the limitations inherent in drawing conclusion from cross-sectional data and, certainly, longitudinal follow-up is needed to truly determine if the variation in peripapillary choroidal thickness is predictive of the development of NAION. However, the findings are consistent across 3 independent studies with similar methodologies suggesting that they are relevant to the disease process and are deserving of further exploration. REFERENCES 1. Loureiro MM, Vianna JR, Danthurebandara VM, Sharpe GP, Hutchison DM, Nicolela MT, Chauhan BC. Visibility of optic nerve head structures with Spectral-domain and swept-source optical coherence tomography. J Glaucoma. 2017;26:92-797. 2. Pérez-Sarriegui A, Munoz-Negrete FJ, Noval S, DeJuan V, Rebolleda G. 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