Is Cataract Surgery a Risk for Developing Nonarteritic Anterior Ischemic Optic Neuropathy?

Cataract surgery is the most frequently performed ophthalmic surgery and has become safer and more efficient over the past 40 years. There are multiple reports of nonarteritic anterior ischemic optic neuropathy (NAION) associated with cataract extraction, but it remains unclear whether this relationship is coincidental or causal. Two experts debate this topic. Pro: Timothy J. McCulley, MD Ischemic optic neuropathies are traditionally categorized in several groups, with NAION representing any variety so long as not related to giant cell arteritis. There are numerous recognized risk factors for NAION, such as factors leading to atherosclerosis, including smoking, hypertension, diabetes, and hyperlipidemia. NAION usually occurs in patients with a structural risk factor, the small or “crowded” optic disc. Other factors such as medications, sleep apnea, and hemodynamic instability may contribute to the development of NAION. Although many intraocular procedures have been reported to trigger NAION, most focus has been on cataract extraction (1–16). Most likely this bias toward cataract extraction is reflective of the large numbers of this type of surgery being performed and is not specific to the procedure. Two types of cataract extraction associated NAION have been reported; immediate type, cases that occurred within hours or days after surgery, and delayed type, cases that occurred weeks to months after surgery and after a period of good vision (1). The immediate type is almost invariably associated with marked elevation in intraocular pressure (IOP) (2). The delayed type occurs days to months after surgery. The mechanism is likely vascular compression from posterior pole edema (16). Leakage from the optic disc vasculature occurs after intraocular surgery, often but not always in association with cystoid macular edema (CME), and has been documented to precede NAION (17–19). Posterior pole edema involving the optic disc likely leads to vascular compression within the optic disc. This is consistent with the observation that many cases of postsurgical NAION followed surgery that was complicated by posterior capsular tear or CME, where optic disc edema is more apt to develop (3). Although the mechanism of delayed type is unconfirmed, there is an overabundance of evidence in support of a causal relationship between intraocular surgery and NAION. It can be broken down into several categories as follows: anecdotal observations, case-controlled comparisons, temporal analysis, and population-based studies. Each is summarized. There is an evergrowing wealth of observation-based reports of the association between intraocular surgery and NAION. As far back as 1951, Townes et al described a series of patients who developed an optic neuropathy after cataract extraction (4). In one review of 565 patients who underwent cataract extraction, 4 patients developed optic neuropathies in weeks to months after cataract extraction. Reese and Carrol (1958) and Carrol (1973) authored large case series characterizing patients who developed NAION after cataract extraction (5,6). In 1980, Hayreh published an important observation (2). He described 13 patients who developed NAION after cataract extraction. His cohort differed from previously published cases. Onset was within hours of surgery and cases were “invariably” associated with perioperative elevations in IOP. This “immediate-type” case differs distinctly from “delayed-type” cases, in that they occur in the perioperative period and have a readily identifiable cause, that is, elevated IOP. In 2003, McCulley et al identified 18 patients who developed NAION within a year of cataract surgery at the Bascom Palmer Eye Institute (BPEI) in Miami (3). These included patients with the immediate-type and delayed-type postsurgical NAION. As expected, those with the immediate type had elevations in IOP. Patients with the delayed type had a high rate of complication, posterior capsular tear, and CME, consistent with the proposed mechanism of posterior pole edema related to postsurgical inflammation. Subsequently, there have been many smaller series describing NAION after intraocular surgery (7–11,20). Case-control studies have compared patient groups with postsurgical NAION to those with spontaneous NAION, with the presumption that a lack of difference would suggest that ischemic events occurring after surgery were coincidental. Conversely, identifying and defining differences would shed light on the role cataract surgery plays. One study found distinct differences between groups; the prevalence of hypertension (29% vs. 68%, P = 0.017) and cup-to-disc ratio ≤0.2 in the involved (60% vs. 94%, P = 0.007) and uninvolved eyes (63% vs. 89%, P = 0.052) was lower in patients with postoperative NAION than those with spontaneous NAION (3). Similar findings were found by the group lead by Neil Miller (21). In their cohort, there were fewer current smokers, fewer patient with hyperlipidemia, and fewer patients with multiple NAION risk factors in the postsurgical NAION than spontaneous NAION group. The relative lack of risk factors, originally reported by McCulley et al and supported by Miller, is consistent with surgery being a causative contributor (3,21). Another noteworthy finding drawn from the data reported by McCulley et al (3) is that within the group of patients with postoperative NAION 33% had a history of NAION in the contralateral eye. This suggests that a history of NAION in the fellow eye may identify patients at an increased risk of postoperative NAION. Given the rarity of optic nerve ischemic events after intraocular surgery, a prospective randomized trial is challenging and arguably infeasible. A temporal analysis is a more pragmatic approach. If cases occurring after cataract extraction were by coincidence, a uniform distribution over time would be expected. In 2003, McCulley et al (1) assessed the timing of NAION after cataract extraction. All cases occurred within 6 months of surgery (mean interval, 35 days; range, 1–130 days), which is significantly different from a uniform distribution (P < 0.001). Similarly, in a series of more than 100 cases of postsurgical NAION performed in Canada, most occurrences were within the first 21 days of surgery, which is vastly different from a uniform distribution (P < 0.001) (13). Another study however failed to identify a temporal association (21), but because of the small size and low power of the study, its data are insufficient to exclude a temporal association (22). Taken together, these analyses strongly argue that optic nerve infarction after cataract surgery is not coincidental but rather precipitated by surgery. Another temporal association is that of patients with bilateral postsurgical NAION. A number of patients have had the misfortune of suffering an ischemic event after sequential surgery in both eyes (3,6,9,10,13,15). Often, the time between surgery and NAION was similar. For example, one such patient described by McCulley et al had onsets on postoperative day 10 and 14 (3). Recently, Bénard-Séguin et al (10) reported (2019) a patient who underwent sequential cataract extraction and developed NAION in both eyes, 3 and 5 weeks postoperatively. In the case series by Ing et al, 4 patients were identified who suffered NAION in both eyes after cataract extraction (13). A number of population-based assessments have also concluded that intraocular surgery increases the risk of NAION. The occurrence of NAION after lens-related surgery was assessed in a large population at BPEI (15). During a 5-year period, between January 1, 1993, and December 31, 1997, a total of 5,787 cataract extraction cases were performed. Within that group, 3 patients developed NAION within 1 year of the procedure. They occurred postoperatively on days 29, 36, and 117, giving an estimated six-month incidence of 51.8 per 100,000 and six-week incidence of 34.6 per 100,000. This is statistically higher than the previously reported overall incidence of NAION (23,24). In 2017, Al-Madani et al (12) compared groups of patients who did and did not undergo cataract extraction. They reported a significantly higher incidence of ischemic optic neuropathy in the surgical group, similarly concluding, “phacoemulsification is a risk factor for NAION, independent of the presence of medical risk factors.” A recent very large study, using the Korean National Health Insurance Service database, similarly identified cataract extraction as a risk factor for NAION, in their study population of 1,025,340 beneficiaries (16). Although adjusting for other risk factors and comorbidities, patients undergoing cataract extraction had an increased risk of developing NAION compared with the nonsurgical group, hazard ratio 1.80. These studies do not address a mechanism; however, they do strongly support the concept that NAION may be triggered by intraocular surgery, even when onset is not in the immediate postoperative period. One population-based study failed to demonstrate an increased NAION occurrence rate in patients undergoing cataract extraction (21). These data were based on cases that were identified by searching the medical record database using a single diagnostic code for NAION. This method likely resulted in an underestimation of the true occurrence rate (22). In contradiction to this, the same study found differences in other risk factors between patients with spontaneous and postsurgical NAION, which does suggest that cataract surgery adds to the risk of developing NAION in their patient population. The risk of postsurgical NAION is likely decreasing as our surgical techniques evolve. In the 1950s, the occurrence rate in Townes et al cohort was roughly 1 per 150 cases (4 occurrences of the 565 surgeries) (4). At that time, cataract surgery was performed using large scleral incisions with extracapsular or intracapsular techniques. The amount of inflammation associated with such surgeries is much greater than that associated with small incision surgery. In the 1990s, after the advent of phacoemulsification, the estimate occurrence rate was lower, roughly 1 per 2000 cases (3 occurrences of the 5,787 cases) (15). More recently (2020), the occurrence rate was estimated to be less than 1 in 10,000 cases (13). As our surgical techniques gain sophistication, complication rates decrease and trauma sustained by the eye diminishes. With less inflammation incited, we may see a further decline in the number of cases of surgery-related NAION. Although the overall incidence of postsurgical NAION may be very low, the danger in downplaying the risk of postsurgical NAION lies in the more tangible risk for patients with a history of NAION in the fellow eye. Patients with a history of NAION in the fellow eye are likely at an increased risk of postsurgical NAION. Reese and Carroll described this in the 1950s (5,6). Combining patients from their 2 series, 8 of 17 patients with a history of NAION after cataract extraction developed NAION after cataract extraction in the second eye. In the series of postoperative NAION assessed by McCulley et al (3), a total of 6 (33%) of 18 cases occurred in patients who had a history of NAION in the contralateral eye. Also included in this cohort were 2 subjects who underwent a second cataract extraction in the fellow eye. One developed NAION after both surgeries. In 2007, Lam et al assessed cataract extraction as a risk factor for NAION in patients with a history of NAION in the fellow eye (14). They found that cataract extraction increased the risk of NAION occurrence by 3.6 times (Cox regression, P = 0.001). In closing, the evidence overwhelmingly supports the observation that intraocular surgery may cause NAION. The risk is likely decreasing as surgical techniques improve. However, until cataract and other intraocular surgery can be performed without any chance of elevation in IOP or postoperative inflammation, some risk will remain. The hazard in underestimating the risk of NAION associated with cataract surgery lies in second eye involvement. It has been estimated that upward of 50% of patients, with a history of NAION, may develop NAION in the fellow eye after cataract extraction (14). In patients with a history of NAION in the fellow eye, prudence is warranted. Considerations include delaying surgery if not essential and judicial control of IOP and postoperative inflammation. Con: Neil R. Miller, MD Cataract surgery is one of the most common and safe procedures performed throughout the world. Nevertheless, rare complications occur, including hemorrhage, infection, and retinal detachment, all of which can cause severe and permanent visual loss (8). In addition to these potential causes of visual loss, an optic neuropathy resembling NAION has been documented to occur after apparently uncomplicated cataract surgery (2,8,25–28), resulting in devastating visual morbidity. In some cases of postcataract surgery optic neuropathy (PCSON), visual loss is present immediately after surgery (the immediate form) (7,8), whereas in others, symptoms develop several days, weeks, or months postoperatively (the delayed form) (1,3–5,7,8,15,20). Some authors have suggested that increased IOP, raised intraorbital pressure from a retrobulbar or peribulbar anesthetic, systemic perioperative hypotension, or a combination of these factors might be responsible for the immediate form (1,2,6,15,29), whereas the causative factors for the delayed form were unclear, although intraocular surgery–related posterior pole edema, resulting in vascular compression of the optic nerve, were proposed (3,30). Most of the initial studies of PCSON included small numbers of patients and there was, for many years, no acceptance of this concept; however, McCulley et al (15) evaluated the incidence of PCSON among 5,787 patients who underwent noncomplex cataract surgery between 1993 and 1997 and identified 3 patients who experienced an acute anterior optic neuropathy within 1 year of the surgery, with an estimated 6-week incidence of 34.6 in 100,000 and a 6-month incidence of 51.8 in 100,000 (95% confidence interval [CI], 10.7–151). These rates were significantly higher than the previously reported incidence of NAION, estimated to be 2.3–10.2 per 100,000 in the general population of people 50 years and older (14,23). The authors thus concluded that cataract surgery was indeed associated with an increased incidence of an acute anterior optic neuropathy. In a subsequent study, McCulley et al (1) evaluated the temporal relationship of cataract surgery to the development of a subsequent anterior optic neuropathy. These investigators reviewed the records of all patients who developed an anterior optic neuropathy between 1993 and 1999 and identified 18 eyes of 17 patients who experienced this disorder within 1 year after surgery. They found that most of these patients developed the optic neuropathy within 6 weeks of surgery, suggesting a decreasing temporal association between the surgery and the optic neuropathy. Because of the resemblance of PCSON to NAION, Lam et al (14) evaluated the risk of PCSON in the fellow eye of 325 patients with previous unilateral spontaneous NAION who were evaluated at the BPEI between 1986 and 2001. Nine of 17 patients (53%) with spontaneous NAION in one eye and who subsequently underwent cataract surgery in the fellow eye developed NAION in that eye, whereas 59 of 308 patients (19%) with spontaneous NAION in one eye but who did not undergo cataract surgery in the fellow eye developed spontaneous NAION in that eye. The figure of was to that of Carroll for the risk of PCSON in the fellow eye of patients who previously had experienced PCSON in their first eye. Lam et al thus concluded that PCSON is a form of NAION and that patients who an of unilateral spontaneous NAION also have a significantly increased risk of PCSON in the fellow eye (95% the development of which has visual for an patient from visual loss in one eye. In a of cataract by Ing et al found that of those cataract who had at one patient who had experienced PCSON and that the estimate incidence was cases per 100,000 procedures the year after the surgery, with of cases occurring within 3 Another recent series from also concluded that there was an increased risk of an acute optic neuropathy after apparently uncomplicated cataract surgery (16). However, there have been in both and surgical techniques the of McCulley et most cataract surgery is performed rather than retrobulbar or peribulbar and the surgery less than 10 in experienced In there is bias in the study by Ing et the authors in the bias from and including and and the Korean authors that in their study, of patients developed an acute optic neuropathy within 3 days and most occurred more than 1 year after the surgery (16). there is at one recent study that into the relationship between cataract surgery performed and et al a of this performed a study of patients at the Eye Institute or one of its to if these had the incidence and prevalence of PCSON (21). In this study, of patients had a history of cataract surgery the year subsequent to developing NAION. these patients, developed visual loss in the immediate postoperative period. This is in to the cohort reported by McCulley et al in which developed visual loss within a days after surgery and the by Ing et al that developed visual loss within 3 weeks after surgery. In a by et al of the of the cases of NAION after cataract surgery an uniform distribution time resulted in their that their cases were more likely spontaneous NAION and not related to the cataract surgery (21). a 5-year study period, among more than patients who underwent cataract surgery at the Eye Institute or one of its 2 experienced an of within 1 year of undergoing incidence of per 100,000 (95% This rate is with the previously reported rate by et al of (95% per 100,000 cases of spontaneous NAION in the general population years In the estimated incidence of NAION within 6 months after cataract surgery in their study was (95% in 100,000. Although the associated of their study were and those of previous the estimated incidence of PCSON in their study was lower than the rate previously reported by McCulley et al (15) of 51.8 in 100,000 that also had a (95% 10.7–151). There are to the study by et al (21), including potential In cases of PCSON may have been because of optic and In the of NAION may have been et al these that the Eye that all patients who present to in the or the Eye Service with or symptoms or be with one of the thus it less likely that a patient with NAION would an In et al that it is common at including its for all patients by in other with or symptoms or to be immediately with a of the although it is that some patients with NAION were et al this et al also reviewed the records of all patients as NAION and in cases in which there was the authors the the the the or a combination of these to a of the cases as NAION in their database, the authors from further because the patients had experienced their of NAION the study period = because of lack of evidence to support the of NAION disc = or because subsequent that the of NAION was and the visual loss was by = their would to have that the patients who were included in the study had they did that if a patient developed NAION after cataract surgery at the Eye Institute or one of its or would have to the Eye Institute or one of its for an This might have resulted in an incidence of they reviewed all eye records to that optic disc was present to support a of a postcataract Patients with evidence of an optic neuropathy but in optic disc was documented thus were from this study, also underestimating the prevalence of if it was posterior rather than Although they might have to other potential risk factors for the development of NAION, such as recent surgery using or surgery, perioperative after surgery occurs and would be to be with spontaneous NAION, and all cases of perioperative after surgery are posterior not anterior the number of patients who had cataract surgery in the fellow eye after developed unilateral NAION in one eye was small = it to the risk of PCSON in the fellow eye of patients with unilateral NAION. In the data by et al suggest that both the prevalence and incidence of NAION after cataract surgery are with those of the general with no temporal relationship between cataract surgery and the subsequent development of NAION in the eye. Timothy J. McCulley, MD The findings of one study, of which Miller was the in are with the findings of (21). Although they did a difference in NAION risk factors between patients with postsurgical and spontaneous NAION, their study failed to identify a temporal association or increased incidence of NAION after cataract extraction. The in this study lies in the of a single diagnostic code to identify cases of NAION. Miller that the at is, at to have patient with with a of the This is of and would to that our diagnostic is our Miller that the of a code other than for a patient with NAION would be is that for optic disc edema, visual and any other number of are also As a of the can with that uniform is not one of our A more study is to into of the and It is very likely that the incidence of NAION after surgery at was by et al (21). with Miller in that the incidence of postsurgical NAION is most likely decreasing and in may be The risk of NAION after intraocular surgery has likely as surgical techniques Miller that in surgery, performed with the risk of optic nerve may be to the risk of developing an NAION. This may be to However, until cataract and other intraocular surgeries are performed without any chance of elevation in IOP, posterior tear, or postoperative inflammation, some risk will remain. The most hazard in underestimating the risk of NAION associated with cataract surgery lies in second eye that upward of 50% of patients, with a history of NAION, may develop NAION in the fellow eye after surgery (14). also very much with that surgery to patients with would be a However, in patients with a history of NAION in the fellow eye, prudence is warranted. For example, surgery in a patient with a history of NAION in the fellow eye, with a of with in is a For at risk judicial control of IOP and postoperative inflammation is also In closing, intraocular surgery including cataract extraction is a risk factor for NAION. Miller and that this risk has almost with in the surgical Although in the risk of postsurgical NAION may be there likely remains a risk for patients with a history of NAION in the fellow eye. In such cases, prudence is warranted. Neil R. Miller, MD The performed by McCulley et al that a relationship between apparently uncomplicated cataract surgery and postoperative optic neuropathy as as the recent by Ing et al and et al in there is no evidence that patients who have experienced NAION in one eye have an increased risk of NAION after noncomplex cataract surgery in the fellow eye although it remains that even cataract surgery in some patients to develop an acute optic neuropathy after apparently uncomplicated cataract surgery, and although with McCulley that this be with any patient surgery in this would not to cataract surgery for the patient who has experienced an acute optic neuropathy within 1 year of apparently uncomplicated cataract surgery or after spontaneous NAION in one eye and who is from a cataract in the fellow eye. MD and MD Although a causal relationship between uncomplicated cataract surgery and NAION may not be there is evidence in that to some and when on the fellow eye in a patient with previous NAION. The risk be with the patient and be to control perioperative IOP and inflammation.

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