Journal of Neuro-Ophthalmology, March 2005, Volume 25, Issue 1

A Comparison of Risk Factors for Postoperative and Spontaneous Nonarteritic Anterior Ischemic Optic Neuropathy

BACKGROUND:: Whether postoperative non-arteritic ischemic optic neuropathy (NAION) is caused by surgery is unsettled. To provide further evidence on this issue, it is useful to compare the characteristics of patients who develop NAION following intraocular surgery to those who develop NAION spontaneously. METHODS:: In a retrospective review of patients diagnosed with NAION between January 1, 1993 and December 31, 1999, 12 cases of NAION in 11 subjects were identified as occurring within 30 days of cataract extraction or intraocular lens exchange (postoperative NAION group). Using Fisher exact test, the prevalence of NAION risk factors (hypertension, diabetes mellitus, hypercholesterolemia, smoking, small cup-to-disc ratios) was compared with that of a similarly aged control group of 37 subjects diagnosed with spontaneous NAION (spontaneous NAION group). RESULTS:: Patients with postoperative NAION had a lower prevalence of hypertension than did those with spontaneous NAION (27% versus 68%, P = 0.034) and a lower prevalence of cup-to-disc ratios of less than or equal to 0.2 (55% vs. 94%, P = 0.006). The prevalence of elevated cholesterol, diabetes mellitus, and tobacco use was similar in the two groups. CONCLUSIONS:: The prevalence of hypertension and low cup-to-disc ratios is significantly lower in subjects with NAION following lens-related intraocular surgery than in those with spontaneous NAION, indicating that risk factors for NAION in these settings may be different.

ORIGINAL CONTRIBUTION A Comparison of Risk Factors for Postoperative and Spontaneous Nonarteritic Anterior Ischemic Optic Neuropathy Timothy J. McCulley, MD, Byron L. Lam, MD, and William J. Feuer, MS Background: Whether postoperative non- arteritic ische­mic optic neuropathy ( NAION) is caused by surgery is un­settled. To provide further evidence on this issue, it is useful to compare the characteristics of patients who develop NAION following intraocular surgery to those who develop NAION spontaneously. Methods: In a retrospective review of patients diagnosed with NAION between January 1, 1993 and December 31, 1999, 12 cases of NAION in 11 subjects were identified as occurring within 30 days of cataract extraction or intra­ocular lens exchange ( postoperative NAION group). Using Fisher exact test, the prevalence of NAION risk factors ( hypertension, diabetes mellirus, hypercholesterolemia, smoking, small cup- to- disc ratios) was compared with that of a similarly aged control group of 37 subjects diagnosed with spontaneous NAION ( spontaneous NAION group). Results: Patients with postoperative NAION had a lower prevalence of hypertension than did those with spontaneous NAION ( 27% versus 68%, P = 0.034) and a lower prevalence of cup- to- disc ratios of less than or equal to 0.2 ( 55% vs. 94%, P = 0.006). The prevalence of elevated cholesterol, diabetes mellirus, and tobacco use was similar in the two groups. Conclusions: The prevalence of hypertension and low cup- to- disc ratios is significantly lower in subjects with NAION following lens- related intraocular surgery than in those with spontaneous NAION, indicating that risk factors for NAION in these settings may be different. ( J Neuro- Ophthalmol 2005; 25: 22- 24) Stanford University School of Medicine ( T. J. M.), Department of Ophthalmology, Stanford, CA; Bascom Palmer Eye Institute ( B. L. L., WJ. E), University of Miami School of Medicine, Miami, FL. Address correspondence to Timothy I McCulley, MD, Stanford University School of Medicine, Department of Ophthalmology, 300 Pasteur Drive, Room A157, Stanford, CA 94305; E- mail: mcculley@ stanford. edu Financial support received in part from a departmental grant from Research to Prevent Blindness. Nonarteritic anterior ischemic optic neuropathy ( NAION) has been reported after various intraocular procedures, including extracapsular cataract extraction by nuclear expression or phacoemulsification, intracapsular cataract extraction, and secondary intraocular lens implan­tation or exchange ( 1- 9). NAION may occur in the immediate postoperative period with spikes in intraocular pressure, as originally described by Hayreh ( 2), or weeks to months postoperatively ( 1- 4). Although the mechanism underlying delayed NAION cases is undetermined, there is substantial evidence supporting a causal relationship to the surgery. We previously determined the incidence of delayed NAION after cataract extraction to be slightly greater than 1 in 2000 surgeries, substantially higher than expected based on the estimated annual incidence of spontaneously occurring NAION of 2.3 to 10.3 of 100,000 ( 5,10,11). Additionally, by analyzing the temporal relationship of 18 cases ( 17 subjects) of NAION occurring within 1 year of anterior segment surgery, we found a significant association between NAION and intraocular surgery. All cases occurred within the first 19 postoperative weeks and none during the remainder of the first postoperative year, contrasting with a more uniform distribution to be expected were the association coincidental ( 1). In this study, we compare the prevalence of NAION risk factors in a sub­group of the previously reported patient sample of 17 subjects with postoperative NAION ( 1) to a similarly aged control group with spontaneous NAION. METHODS By reviewing the medical records of patients with NAION diagnosed between January 1, 1993 and December 31, 1999, 11 patients ( six male, five female; mean age 75 years, range 64 to 85 years) were identified as having NAION develop within 30 days of intracapsular or extracapsular cataract extraction, secondary intraocular lens placement, or intraocular lens exchange ( postoperative NAION group). A similarly aged control group consisting of 37 patients ( 19 male, 18 female; mean age 71 years, range 50 to 87 years) with spontaneously occurring NAION was 22 J Neuro- Ophthalmol, Vol. 25, No. 1, 2005 Postoperative NAION J Neuro- Ophthalmol, Vol. 25, No. 1, 2005 randomly selected from the same medical record database ( spontaneous NAION group). The diagnosis of NAION was based on the following criteria: ( 1) acute decrease in vision; ( 2) nerve fiber layer defect on visual field testing; ( 3) relative afferent pupillary defect; ( 4) observed optic nerve edema or segmental pallor, if acute visual loss occurred 6 weeks or longer before examination; and ( 5) an appropriate evaluation had been performed to exclude alternative causes. The number of subjects with hypertension, diabetes mellitus, hypercholesterolemia, tobacco use, and cup- to- disc ratio of 0.2 or less in the affected and fellow eyes was obtained for both the postoperative and spontaneous NAION groups. The Fisher exact test was used to assess differences between groups. RESULTS Table 1 summarizes the results of the 11 patients ( 12 eyes) in the study group. Four ( 36%) were the immediate type, occurring within 24 hours of surgery, and seven ( 64%) were of the delayed type. Extensive detail and analysis regarding the times of onset has been previously published ( 1). Table 2 summarizes the NAION risk factors for the postoperative and spontaneous NAION groups. The prevalence of hypertension and small cup- to- disc ratio was significantly lower in the postoperative NAION group than in the spontaneous NAION group. The prevalence of hypertension among the seven patients with delayed postoperative NAION was lower than in the spontaneous NAION group ( 43%> vs. 68%>), but the difference was not statistically significant ( P - 0.24). The occurrence of a small cup- to- disc ratio in the affected eye of the patients with delayed postoperative NAION was statistically lower than in the eyes of the spontaneous NAION group ( 57% vs. 94%; P = 0.028). The prevalence of diabetes mellitus, hypercholesterolemia, and tobacco use was similar in the two groups. DISCUSSION When the prevalence of NAION risk factors was compared between patients with postoperative NAION and a control group of similarly aged patients with spontaneous NAION, the prevalence of hypertension and small cup- to-disc ratio was notably lower in patients with postoperative NAION. This finding suggests that persons who have larger cup- to- disc ratios are also at risk for postoperative NAION. Although the exact mechanism has not been established, NAION is thought to be caused by microvas­cular hypoperfusion of the posterior ciliary arteries. NAION occurring during the first 24 hours after surgery has been reported to be associated with high intraocular pressures ( 1,2). Elevation in intraocular pressure likely impedes the blood flow to the optic nerve head, resulting in infarction. Although cases of immediate postoperative TABLE 1. Characteristics of 11 patients with postoperative nonarteritic anterior ischemic optic neuropathy ( NAION) Patient No. 1 2 3 4 5 6 7a** 7b** 8 9 10 11 Age/ Sex 69/ F 73/ M 78/ F 73/ M 75/ M 64/ M 79/ F 79/ F 72/ M 76/ F 84/ M 85/ F < su rgery Technique Complications Phaco Phaco * * * ECCE Phaco Phaco Phaco Phaco Phaco * PC Tear None * * CME None None None None None None * NAION Onset Postoperative Day 1 1 1 1 3 5 10 14 11 29 30 30 IOPon Postoperative Day 1 52 45 45 * * * * * * 16 * * C: D Ratio Involved Uninvolvec Eye 0 .3 .3 .2 .3 .15 .1 .1 .1 .3 .3 .2 Eye 0 .3 .3 .2 .3 .15 .1 .1 .1 .3 .3 .2 1 Atherosclerotic Risk Factor HTN DM HC Smoking N N N N N Y N N Y Y N N N N N Y N N N N Y N Y N N Y N N N N Y Y N N N N N Y N N N N N N N N N N History of Spontaneous NAION N N N Y N N N Y N Y N N C: D ratio = cup to disc ratio; CME = cystoid macular edema; DM = diabetes mellitus; ECCE = extra- capsular cataract extraction by expression; HC = hypercholesterolemia; HTN = hypertension; ICCE = intra- capsular cataract extraction; IOL = intra- ocular lens; IOP = intra- ocular pressure; N = not present; PC Tear = posterior capsule tear; Phaco = extra- cap sular cataract extraction by phacoemulsification; Y = yes present. information not available. " Developed bilateral consecutive postoperative NAION. 7a applies to OD, and 7b applies to OS. 23 J Neuro- Ophthalmol, Vol. 25, No. 1, 2005 McCulley et al TABLE 2. Prevalence of risk factors in patients with postoperative and spontaneous nonarteritic anterior ischemic optic neuropathy Variable Postoperative Spontaneous NAION NAION ( n = l l ) ( n= 37) Cup- to- disc ratio < 0.2 Affected eye Fellow eye Diabetes mellitus Hypercholesterolemia Hypertension Tobacco use 55 ( 6/ 11) 55 ( 6/ 11) 27 ( 3/ 11) 18 ( 2/ 11) 27 ( 3/ 11) 9( 1/ 11) 94 ( 32/ 34) 89 ( 32/ 36) 24 ( 9/ 37) 35 ( 13/ 37) 68 ( 25/ 37) 16 ( 6/ 37) 0.006 0.23 1.00 0.46 0.034 1.00 NAION = Nonarteritic anterior ischemic optic neuropathy. Figures are % ( n/ N). NAION have been reported without a documented eleva­tion in intraocular pressure, transient increases in in­traocular pressure during the operative and perioperative periods in these patients may have occurred. In support of the association between increased intraocular pressure and immediate postoperative NAION was the finding that of four patients with the immediate type of postoperative NAION in our study, three had documented intraocular pressure measurements of 45 mm Hg or higher. The causal relationship between the delayed type of postoperative NAION and intraocular surgery is less clear. One possible mechanism may be posterior pole edema related to surgical compression of optic nerve microvas-culature. Optic disc edema has been observed preceding the onset of visual symptoms of NAION ( 12- 14). Also, the occurrence of optic nerve edema without visual dysfunction has been reported weeks to months after cataract extraction ( 15,16). In patients with tenuous blood perfusion of the optic nerve head, minimal edema, possibly subclinical, may result in NAION weeks to months after surgery. 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