Surgery for nonarteritic anterior ischemic optic neuropathy.

Cochrane Database of Systematic Reviews

Surgery for nonarteritic anterior ischemic optic neuropathy (Review) Dickersin K, Li T

Dickersin K, Li T. Surgery for nonarteritic anterior ischemic optic neuropathy. Cochrane Database of Systematic Reviews 2015, Issue 3. Art. No.: CD001538. DOI: 10.1002/14651858.CD001538.pub4.

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Surgery for nonarteritic anterior ischemic optic neuropathy (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Optic nerve decompression surgery and careful follow-up versus careful follow-up alone, Outcome 1 Improvement of 3 or more lines of vision at six months. . . . . . . . . . . . . . . . Analysis 1.2. Comparison 1 Optic nerve decompression surgery and careful follow-up versus careful follow-up alone, Outcome 2 Improvement of 3 or more lines of vision at 24 months. . . . . . . . . . . . . . . . ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .


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[Intervention Review]

Surgery for nonarteritic anterior ischemic optic neuropathy Kay Dickersin1 , Tianjing Li2 1 Center for Clinical Trials and US Cochrane Center, Johns Hopkins University, Baltimore, MD, USA. 2 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

Contact address: Kay Dickersin, Center for Clinical Trials and US Cochrane Center, Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe Street, Mail Rm E6152, Baltimore, MD, 21205, USA. [email protected]. Editorial group: Cochrane Eyes and Vision Group. Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 3, 2015. Review content assessed as up-to-date: 23 October 2014. Citation: Dickersin K, Li T. Surgery for nonarteritic anterior ischemic optic neuropathy. Cochrane Database of Systematic Reviews 2015, Issue 3. Art. No.: CD001538. DOI: 10.1002/14651858.CD001538.pub4. Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT Background Nonarteritic anterior ischemic optic neuropathy (NAION) is characterized by sudden and painless loss of vision in the eye, accompanied by pallid swelling of the optic disc. Its etiology is unknown and no medical therapy has been proven effective in treating this condition. Optic nerve decompression surgery, a proposed treatment for NAION, involves making two or more slits or a window in the tissue surrounding the optic nerve, thereby allowing cerebrospinal fluid to escape, and theoretically reducing the pressure surrounding the optic nerve. Objectives The objective of this review was to assess the safety and efficacy of surgery compared with other treatment or no treatment in people with NAION. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2014), EMBASE (January 1980 to October 2014), PubMed (1948 to October 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 23 October 2014. Selection criteria All randomized trials of surgical treatment of NAION were eligible for inclusion in this review. Data collection and analysis From full-text copies of all reports from relevant trials, one author extracted data which were verified by another author. No data synthesis was required. Surgery for nonarteritic anterior ischemic optic neuropathy (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Main results The one included trial, in which 258 participants were randomized, was stopped early for futility. At the time of the 24-month report the follow-up rate was 95.3% for six months and 67.4% for 24 months (174 participants; 89 careful follow-up and 85 surgery). There was no evidence of a benefit of surgery on visual acuity. Measurements of visual acuity and visual fields were performed by a technician masked to the treatment received. At six months 32.0% of the surgery group had improved visual acuity by 3 or more lines compared with 42.6% of the careful follow-up group (unadjusted risk ratio (RR) 0.75, 95% confidence interval (CI) 0.54 to 1.04). At 24 months 29.4% of the surgery group had improved compared with 31.0% of the careful follow-up group (unadjusted RR 0.95, 95% CI 0.60 to 1.49). Participants who underwent surgery more often lost 3 or more lines of visual acuity in the study eye, although the increased risk was not statistically significant. At six months 18.9% in the surgery group had worsened visual acuity in the study eye compared with 14.8% in the careful follow-up group (RR 1.28; 95% CI 0.73 to 2.24). At 24 months 20.0% in the surgery group had worsened visual acuity in the study eye compared with 21.8% in the careful follow-up group (RR 0.92; 95% CI 0.51 to 1.64). Participants who received surgery experienced both intraoperative and postoperative adverse events, including central retinal artery occlusion during surgery and light perception vision at six months (one participant); and immediate loss of light perception following surgery and loss of vision that persisted to the 12-month visit (two participants). In the careful follow-up group, two participants had no light perception at the sixmonth follow-up visit; one of these had improved to light perception at 12 months. Pain was the most common adverse event in the surgery group (17% in surgery group versus 3% in the careful follow-up group at one week). Diplopia (double vision) was the next most common complication (8% in the surgery group versus 1% in the careful follow-up group at one week); at three months there was no statistically significant difference in proportion of participants with diplopia between the two groups. Authors’ conclusions The only eligible trial provided no evidence of a beneficial effect of optic nerve decompression surgery for NAION. Future research should focus on increasing our understanding of the etiology and prognosis of NAION. New treatment options should be examined in the context of randomized clinical trials.

PLAIN LANGUAGE SUMMARY Surgery to improve vision in people with nonarteritic anterior ischemic optic neuropathy (NAION) Review question This review looked at the evidence about the safety and effectiveness of surgery (optic nerve decompression surgery) compared with no treatment on the vision of people with nonarteritic anterior ischemic optic neuropathy (NAION). Background NAION is a sudden and painless loss of vision in the eye attributed to swelling of the area inside the eye where the optic nerve connects to it. The swelling of the tissue puts pressure on the optic nerve, and it is believed that this pressure interrupts the blood supply to the optic nerve, causing loss of vision. The cause of NAION is not known. No treatment has been proven to help. A proposed treatment for NAION is called optic nerve decompression surgery. This surgery makes two slits or a window in the swollen eye tissue surrounding the optic nerve. These slits allow fluid building up around the optic nerve to escape. The hope is that this would reduce the pressure on the optic nerve and vision would improve. Study characteristics The search for studies was done on 23 October 2014. One study (a randomized controlled trial) was found. There were 258 participants in the trial. These 258 people were randomly divided into two groups. One group received the optic nerve decompression surgery along with careful follow-up. The other group received careful follow-up alone. Careful follow-up included an ophthalmologic examination at each study visit and visual field testing at 12 months and as needed. The technician performing the follow-up tests did not know to which group the participants belonged (surgery or no surgery). Funding for this trial was provided by National Eye Institute, USA. Key results The trial was stopped early because the surgery was not helping the participants more than careful follow-up alone. The trial found no evidence of benefit from the surgery, but there were several harms caused by the surgery, such as further vision loss. Pain and double Surgery for nonarteritic anterior ischemic optic neuropathy (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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vision were harms experienced by some participants in the surgery group at one week after the surgery. The trial investigators reported that continued enrollment would be unlikely to produce results in favor of surgery. Quality of the evidence The quality of evidence in this one trial is considered high.

BACKGROUND Description of the condition Nonarteritic anterior ischemic optic neuropathy (NAION) is a common cause of acute optic nerve disease in the elderly (Hayreh 1975; Hayreh 1981; Hayreh 1990) and results in visual loss. NAION is clinically characterized by sudden and painless loss of vision in one eye, accompanied by pallid swelling of the optic disc (optic nerve head). Estimates of the annual incidence rate of NAION in the United States range from approximately 2.3 per 100,000 individuals (Johnson 1994) to 10.3 per 100,000 individuals (Hattenhauer 1997). Its etiology is unknown. Visual function of the affected eye may be impaired through decreased central visual acuity, peripheral visual field loss, or both.

Types of studies We included randomized controlled trials of surgical treatment of NAION in this review. Types of participants We included trials of people with NAION, however defined by the investigator. We imposed no gender or age limitations. Types of interventions We included trials in which any form of surgical treatment for NAION in the experimental group had been compared with any other treatment, including usual care. Types of outcome measures

Description of the intervention Although various medical interventions, such as corticosteroids and phenytoin sodium, have been used to treat NAION, no therapy has been proven effective. Sergott 1989 suggested that optic nerve decompression surgery might improve vision in people with NAION. Optic nerve decompression surgery involves making two or more slits or a window in the tissue surrounding the optic nerve, thereby allowing cerebrospinal fluid to escape and, theoretically, reducing the pressure surrounding the optic nerve.

OBJECTIVES The objective of this review was to assess the safety and efficacy of surgery compared with other treatment or no treatment in people with NAION.

Primary outcomes

The primary outcome for comparison of treatments was change in visual acuity (measured as either improved vision or worsened vision).

Secondary outcomes

The secondary outcomes for comparison of treatments were: 1. change in visual field; 2. occurrence of NAION in the fellow eye; 3. adverse events and safety of optic nerve decompression surgery; 4. quality of life of participants.

Search methods for identification of studies METHODS Electronic searches

Criteria for considering studies for this review

We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 10), Ovid MEDLINE,


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Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2014), EMBASE (January 1980 to October 2014), PubMed (1948 to October 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 23 October 2014. See: Appendices for details of search strategies for CENTRAL (Appendix 1), MEDLINE (Appendix 2), EMBASE (Appendix 3), PubMed (Appendix 4), mRCT (Appendix 5), ClinicalTrials.gov (Appendix 6) and the ICTRP (Appendix 7). Searching other resources We searched the reference lists of reports from the included trial for any additional trials not identified by the electronic searches.

(masking of outcome assessors), attrition bias (intent-to-treat analyses and losses to follow-up), and reporting bias (selective outcome reporting). Two authors independently judged each included trial for each type of bias as having low risk, high risk, or unclear risk. Measures of treatment effect We analyzed the primary outcome, change in vision from baseline, classified as either improved vision or worsened vision, as a dichotomous outcome. We reported the measure of effect as a risk ratio (RR) with 95% confidence interval (CI) based on the proportion of participants with the event in each group. We also reported the risk ratio reduction (RRR), calculated as the RR − 1 = (risk in surgery group − risk in control group)/risk in control group. Secondary dichotomous outcomes were reported the same way. For continuous outcome data, we reported the measure of effect as the mean difference between intervention and control group. Unit of analysis issues

Data collection and analysis

The unit of analysis was the participant (one study eye per participant).

Selection of studies

Dealing with missing data

Two authors independently screened all records from the original and updated search results. For records classified by at least one review author as definitely relevant or potentially relevant, we obtained the full-text report and assessed the study for eligibility. Two authors independently reviewed the full-text reports and assessed each study for inclusion or exclusion. We documented reasons for excluding studies from the review. We resolved discrepancies between the two authors by discussion.

We used the data available in trial reports and did not impute data for the purposes of this review.

Data extraction and management One author extracted data from information contained in the identified trial reports and another author verified the data extracted. One author entered data directly into RevMan software for analysis and second review author verified the data entry (RevMan 2014).

Assessment of heterogeneity We did not assess heterogeneity as only one trial was included. When future trials are included, we will assess potential clinical and methodological heterogeneity based on the characteristics of participants, interventions, and outcomes in the included trials. We will use the I² statistic to examine heterogeneity and consider an I² greater than 60% as an indication of substantial statistical heterogeneity. If substantial heterogeneity is present, we will not combine results in meta-analysis and instead report trial results independently. Assessment of reporting biases

Assessment of risk of bias in included studies No formal assessment using quality assessment forms or scoring was done for this review prior to 2011. For the 2011 update of this review, each included trial was assessed for risk of bias according to guidelines set forth in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). The types of bias examined were selection bias (random sequence generation and allocation concealment before randomization), performance bias (masking of participants and trial personnel), detection bias

We did not assess for publication bias as only one trial was included. When 10 or more trials are included in meta-analysis, we will assess potential reporting bias by examining the symmetry of a funnel plot. We assessed selective outcome reporting at the trial level as part of the assessment of risk of bias. Data synthesis We did not perform quantitative data synthesis as only one trial was included.


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Subgroup analysis and investigation of heterogeneity We did not perform subgroup analysis. Sensitivity analysis We did not perform sensitivity analysis.

RESULTS

Description of studies

Results of the search From the original search in 1999, we obtained eight potentially relevant full-text reports and examined the corresponding trials for eligibility. We excluded seven reports (see ’Characteristics of excluded studies’ table) and identified one eligible trial. An updated search in 2005 identified 381 new reports. We obtained full-text reports for six potentially relevant records and examined

them for eligible trials. These six reports described details of the single trial already included in the review (IONDT). An updated search in July 2007 yielded a further 71 records of studies. The Trials Search Coordinator scanned the search results and removed any references which were not relevant to the scope of the review. The search did not identify any new trials which met the inclusion criteria for the review. Another updated search in November 2011 yielded 272 additional records. After duplicate review by two review authors, only one new report was added to the review which was an additional publication of the already included trial. The search also identified 18 clinical trial registrations, two of which were for the IONDT study (one for the original trial and one for the follow-up study) and 16 which were not relevant to this review. Another updated search in October 2014 yielded 566 additional titles and abstracts and 73 clinical trial registrations (Figure 1). Two review authors independently screened all records and identified no new studies; however, two additional reports from the IONDT study were included. These two reports were conference abstracts of baseline trial data presented at the Association for Research in Vision and Ophthalmology (ARVO) annual meetings (one in 1995 and one in 2006) and did not provide any information additional to what has been reported in the trial’s journal publications.


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Figure 1. Study flow diagram.

Included studies The IONDT was a randomized trial comparing optic nerve decompression surgery plus careful follow-up to careful follow-up without treatment (see ’Characteristics of included studies’ table). Participants were people 50 years of age or older who had been diagnosed with nonarteritic anterior ischemic optic neuropathy (NAION) within 14 days before enrollment and had best-corrected visual acuity (BCVA) of 20/64 or worse in the affected eye at baseline. Participants in the surgery and careful follow-up groups were examined at one week, one month, three months, six months, and 12 months after randomization and at six-month intervals thereafter. Careful follow-up included an ophthalmologic examination and measurement of BCVA at all follow-up visits and a visual field test at 12-months follow-up and as needed. The IONDT also included follow-up of a non-randomized cohort.

The IONDT enrolled 258 participants (258 eyes) randomized to optic nerve decompression surgery plus careful follow-up to careful follow-up without treatment. Enrolment into this trial was stopped earlier than planned and preliminary results were published (IONDT 1995). The preliminary article reported outcomes on all participants with six months of follow-up at the time the trial was stopped for futility; subsequent papers reported outcomes at 24 months or longer. Visual field data presented in this review were taken from the visual field follow-up reports (IONDT 2000; IONDT 2008). All other data presented in this review were taken from the 24-month report unless otherwise stated (IONDT 2000). Of those randomized, 124/131 careful follow-up and 122/127 surgery participants completed six months of follow-up; 89/131 and 85/127 participants in each group, respectively, completed 24 months of follow-up. The analysis was based on participants with data for both baseline


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and the follow-up visit; two participants in the careful follow-up group and one participant in the surgery group without baseline visual acuity data were not included in the analysis. Comparison of participants with baseline data and 24-month data were similar between groups (Table 1). Excluded studies We excluded seven studies after full text review: five studies were uncontrolled case series and two studies were trials that used concurrent, non-randomized controls (see ’Characteristics of excluded studies’ table).

Risk of bias in included studies

Allocation Randomization was stratified by clinic, with allocations within each clinic balanced across treatment groups. Randomization was performed by the coordinating center, and clinical centers received each treatment assignment by telephone and fax, but only after sending key information on an eligible participant candidate. Masking (performance bias and detection bias) Measurements of visual acuity and visual fields were performed according to a uniform protocol, by an IONDT-certified technician masked to the treatment assignment. Incomplete outcome data Participants were analyzed as part of the treatment group to which they were assigned; however, participants with missing baseline or follow-up data were excluded from the analyses. Furthermore, visual fields were scored for reliability; and visual fields judged to be unreliable were excluded from the analysis. Two participants randomized to the careful follow-up group underwent surgery and were analyzed as part of the surgical group for visual-field outcomes. Selective reporting Results for all study outcomes were reported for the follow-up times specified in the study protocol. Unadjusted risk ratios and adjusted odds ratios were presented. Other potential sources of bias The study was stopped early for futility. The Data and Safety Monitoring Committee for the study determined that continued enrollment would not statistically affect the results sufficiently to favor surgery (IONDT 1995).

Effects of interventions

Visual acuity

At six months, 42.6% (52/122) of participants in the careful follow-up group had BCVA that had improved by 3 or more lines from baseline; a further 42.6% (52/122) of study eyes had little or no change in vision from baseline. In the surgery group 32.0% (39/122) of eyes had improved BCVA by 3 or more lines and 49.2% (60/122) had little or no change from baseline BCVA. At 24 months, the BCVA of 31.0% (27/87) of participants in the careful follow-up group had improved by 3 or more lines and 47.1% (41/87) had little or no change. In the surgery group the BCVA of 29.4% (25/85) of eyes had improved by 3 or more lines and 50.6% (43/85) had little or no change from baseline. Using all participants randomized as the denominator, 39.7% (52/ 131) of careful follow-up and 30.7% (39/127) of surgery participants had BCVA in the study eye improved by 3 or more lines at six months. At 24 months 20.6% (27/131) of careful follow-up and 19.7% (25/127) of surgery participants had improved BCVA in the study eye. There was no statistically significant difference in improvement by 3 or more lines of BCVA between surgery and careful follow-up groups at three, six, 12, or 24 months of follow-up. The unadjusted risk ratio (RR) was 0.78 (95% confidence interval (CI) 0.55 to 1.10) at three months, 0.75 (95% CI 0.54 to 1.04) at six months, 0.84 (95% CI 0.60 to 1.18) at 12 months, and 0.95 (95% CI 0.60 to 1.49) at 24 months (fewer eyes in the surgery group had improvement in BCVA than in the careful follow-up group). We calculated the risk ratio reduction (RRR), and its 95% confidence interval, for BCVA improvement by 3 or more lines at six months follow-up as RRR = RR − 1 = (risk in surgery group − risk in control group)/risk in control group (Detsky 1985). In this case, RRR represents the relative increase/decrease in proportion of participants with improvement in BCVA in the surgery group compared with that in the careful follow-up group. A RRR greater than zero means that a greater proportion of participants improved in BCVA by 3 or more lines in the surgery group compared with the careful follow-up group, i.e., surgery was beneficial compared with careful follow-up for people with NAION. Conversely, a RRR less than zero indicates that careful follow-up is beneficial compared to surgery for people with NAION. Data from the IONDT yield a RRR of 0.25 in favor of careful followup (RR − 1 = 0.75 − 1 = −0.25, 95% CI −0.46 to 0.04). In addition, participants undergoing surgery experienced a greater risk of losing 3 or more lines of BCVA. At three months, 18.3% of study eyes in the surgery group had BCVA worse than baseline BCVA compared with 9.1% of eyes in the careful follow-up group (RR 2.02, 95% CI 1.02 to 3.97). At six months, 18.9% in the surgery group had worsened BCVA compared with 14.8% in the careful follow-up group (RR 1.28, 95% CI 0.73 to 2.24). At 12 months, 15.9% of eyes in the surgery group had worsened BCVA


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compared with 15.8% of eyes in the careful follow-up group (RR 1.01, 95% CI 0.55 to 1.85). At 24 months, 20.0% of eyes in the surgery group had worsened BCVA compared with 21.8% of eyes in the careful follow-up group (RR 0.92, 95% CI 0.51 to 1.64).

Experience of surgeon

According to the preliminary report there was no evidence of apparent benefit to participants operated on by more experienced surgeons, regardless of how experience was defined (IONDT 1995). There was insufficient evidence to support the theory that participants defined as having ’progressive’ NAION fared better than other people in either group. Findings of no evidence of benefit and possibly greater visual loss in the surgery group were consistent across subgroups.

Adverse events

Participants who received surgery experienced both intraoperative and postoperative adverse events, as reported in the preliminary paper (IONDT 1995). These included central retinal artery occlusion during surgery and light perception vision at six months (one participant); and immediate loss of light perception following surgery and loss of vision that persisted to the 12-month visit (two participants). In the careful follow-up group, two participants had no light perception at the six-month follow-up visit; one of these had improved to light perception at 12 months. Pain was the most common adverse event in the surgery group (17% in surgery group versus 3% in the careful follow-up group at one week). Diplopia (double vision) was the next most common complication (8% in the surgery group versus 1% in the careful follow-up group at one week); at three months there was no statistically significant difference between the two groups in proportion of participants with diplopia.

Visual field

Visual field measurement was the basis of a secondary outcome of IONDT, with mean deviation from normal sensitivity as the parameter of interest. According to the preliminary report from the IONDT, there was no evidence of an effect of surgery compared with careful follow-up in terms of change in mean deviation of visual field at three, six, or 12 months. The treatment effect (change in mean deviation in the surgery group minus change in mean deviation in the careful follow-up group), adjusted for mean deviation at randomization in a multiple linear regression model, was −1.00 (standard error (SE) 0.93; P = 0.29) at three months; −0.18 (SE 1.01; P = 0.86) at six months; and −0.56 (SE 1.17; P = 0.63) at 12 months. Thus, there was more loss of sensitivity in the surgery group. At 12-months follow-up, shifts in visual field defects (patterns) were compared to baseline by visual field location. No pattern shifts were observed for superior (Table 2) or inferior (Table 3) defects, either overall (P = 0.22 and 0.68 for superior and inferior locations, respectively; Stuart Maxwell test for homogeneity); or between surgery and careful follow-up groups (P = 0.61 and 0.66 for superior and inferior locations, respectively; Score test for trends of odds). A statistically significant pattern shift toward improvement was found in the central location (Table 4) for all randomized participants (P = 0.02; Stuart Maxwell test for homogeneity); however, this change did not differ between surgery and careful follow-up groups (P = 0.68; Score test for trends of odds). Similarly, there was no difference in defect density (severity) in the surgery group compared with the careful follow-up group. Among all randomized participants, superior altitudinal and inferior altitudinal defect classifications were less severe at 12-months followup compared with baseline to a statistically significant degree (P = 0.008 and 0.001 for superior altitudinal and inferior altitudinal defects, respectively).

Incidence of NAION in the fellow eye

Over the course of participant follow-up, the incidence of second eye NAION was evaluated in both randomized (258) and non-randomized (160) participants. Non-randomized participants were people with NAION and vision better than 20/64 at baseline, as well as eligible participants who refused randomization. Occurrence of NAION in the fellow eye was assessed based on the best clinical judgement of the study neuro-ophthalmologist, surrogate provider, or particpant report. Overall, 14.7% of people at risk for NAION (48/326) experienced new NAION in the fellow eye over approximately five years. Incidence was greater for the randomized compared to the non-randomized participants (17.4% (35/201) versus 10.4% (13/125)).

Quality of life

No data were available on health-related quality of life outcomes.

DISCUSSION

Summary of main results The IONDT investigators found no evidence of benefit of optic nerve decompression surgery compared with careful follow-up without treatment in terms of improvement in visual acuity by 3 or more lines at six, 12 or 24 months. Spontaneous improvement in visual acuity was higher than expected in the careful follow-up group. At three and six months of follow-up, more participants who had surgery in the study eye lost 3 or more lines of visual


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acuity compared with those assigned to careful follow-up alone, although the difference in risk was not statistically significant three months after randomization.

Overall completeness and applicability of evidence Data from the IONDT yielded a RRR of 0.25 in favor of careful follow-up at six months. The 95% CI for RRR of improvement in vision indicates that the data from the IONDT are compatible with a RRR of as much as +0.04 (in favor of surgery) or −0.46 (in favor of careful follow-up). Thus, data from the IONDT indicate that surgery is unlikely to be associated with a clinically meaningful beneficial effect. Thus, we believe that a clinically-meaningful beneficial effect with surgery (improvement in vision by 3 or more lines) in people undergoing optic nerve decompression surgery for NAION at sixmonth follow-up can be ruled out with reasonable confidence.

Implications for practice There is no evidence of a beneficial effect on visual acuity or the visual field from optic nerve decompression surgery in people with NAION, including people with progressive disease. People who receive careful follow-up alone may improve spontaneously (about 31% at 24 months). An estimated 14.7% of participants at risk experienced new NAION in the fellow eye over the five-year follow-up period. Along with the observation of immediate loss of light perception in two participants in the surgery group and other adverse events summarized above, a lack of a clinically meaningful benefit with surgery argues against prescribing optic nerve decompression surgery for people with NAION.

Implications for research Future research should focus on increasing our understanding of the etiology and prognosis of NAION. New treatment options should be evaluated in the context of randomized controlled trials that have appropriate outcomes, including both clinical and participant-reported outcomes.

Potential biases in the review process The main limitation of this review is that it is based on a single trial. There do not appear to be any inconsistencies in the data. Participants in the IONDT were followed for up to five years. Additional published follow-up data from the IONDT and any data from future eligible trials will be included in updates to this review.

AUTHORS’ CONCLUSIONS

ACKNOWLEDGEMENTS Dr Eric Manheimer contributed as a co-author to previous versions of this review: he drafted the original review, including all tables and meta-analysis plots, addressed reviewers’ comments, and double-checked reports for eligibility/exclusion. Jasmine Gatti and Olga Lurye contributed to various aspects of the preparation of the first published version of this review, Swaroop Vedula to the 2005 update, and Kristina Lindsley to the 2012 and 2015 updates. The Cochrane Eyes and Vision Group prepared and executed the electronic search strategies. We are grateful to James Acheson for peer review comments on the first version of this review.

REFERENCES

References to studies included in this review IONDT {published data only} Feldon SE. Computerized expert system for evaluation of automated visual fields from the Ischemic Optic Neuropathy Decompression Trial: methods, baseline fields, and sixmonth longitudinal follow-up. Transactions of the American Ophthalmological Society 2004;102:269–303. Feldon SE, Levin L, Scherer RW, Arnold A, Chung SM, Johnson LN, et al. Development and validation of a computerized expert system for evaluation of automated visual fields from the Ischemic Optic Neuropathy Decompression Trial. BMC Ophthalmology 2006;6:34. Feldon SE, Scherer RW, Levin L, Kelman SE, Dickersin K. Visual fields in the Ischemic Optic Neuropathy

Decompression Trial (IONDT): baseline and change over time. Investigative Ophthalmology and Visual Science 2006; Vol. 47:ARVO E-Abstract 1087. Newman NJ, Scherer R, Langenberg P, Kelman S, Feldon S, Kaufman D, et al. The fellow eye in NAION: report from the ischemic optic neuropathy decompression trial followup study. American Journal of Ophthalmology 2002;134(3): 317–28. Scherer RW, Feldon SE, Levin L, Langenberg P, Katz J, Keyl PM, et al. Visual fields at follow-up in the Ischemic Optic Neuropathy Decompression Trial: evaluation of change in pattern defect and severity over time. Ophthalmology 2008; 115(10):1809–17. The Ischemic Optic Neuropathy Decompression Trial Research Group. Characteristics of patients with


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nonarteritic anterior ischemic optic neuropathy eligible for the Ischemic Optic Neuropathy Decompression Trial. Archives of Ophthalmology 1996;114(11):1366–74. ∗ The Ischemic Optic Neuropathy Decompression Trial Research Group. Ischemic Optic Neuropathy Decompression Trial: twenty-four-month update. Archives of Ophthalmology 2000;118(6):793–8. The Ischemic Optic Neuropathy Decompression Trial Research Group. Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy (NAION) is not effective and may be harmful. JAMA 1995;273(8): 625–32. The Ischemic Optic Neuropathy Decompression Trial Research Group. The Ischemic Optic Neuropathy Decompression Trial (IONDT): design and methods. Controlled Clinical Trials 1998;19(3):276–96. The Ischemic Optic Neuropathy Decompression Trial Research Group. The Ischemic Optic Neuropathy Decompression Trial (IONDT): design and methods. Investigative Ophthalmology and Visual Science 1995; Vol. 36:ARVO E-Abstract 4868.

References to studies excluded from this review Glaser 1994 {published data only} Glaser JO, Teimory M, Schatz NJ. Optic nerve sheath fenestration for progressive ischemic optic neuropathy: results in second series consisting of 21 eyes. Archives of Ophthalmology 1994;112(8):1047–50. Kelman 1991 {published data only} Kelman SE, Elman MJ. Optic nerve sheath decompression for non-arteritic ischemic optic neuropathy improves multiple visual function parameters. Archives of Ophthalmology 1991;109(5):667–71. Plotnik 1993 {published data only} Plotnik JL, Kosmorsky GS. Operative complications of optic nerve sheath decompression. Ophthalmology 1993; 100(5):683–90. Sergott 1989 {published data only} Sergott RC, Cohen MS, Bosley TM, Savino PJ. Optic nerve decompression may improve the progressive form of nonarteritic ischemic optic neuropathy. Archives of Ophthalmology 1989;107(12):1743–54. Spoor 1991 {published data only} Spoor TC, Wilkinson MJ, Ramocki JM. Optic nerve sheath decompression for the treatment of progressive nonarteritic ischemic optic neuropathy. American Journal of Ophthalmology 1991;111(6):724–8. Spoor 1993 {published data only} Spoor TC, McHenry JG, Lau-Sickon L. Progressive and static nonarteritic ischemic optic neuropathy treated by optic nerve sheath decompression. Ophthalmology 1993; 100(3):306–11. Yee 1994 {published data only} Yee RD, Selky AK, Purvin VA. Outcomes of optic nerve sheath decompression for nonarteritic ischemic optic

neuropathy. Journal of Neuro-Ophthalmology 1994;14(2): 70–6.

Additional references Detsky 1985 Detsky AS, Sackett DL. When was a “negative” clinical trial big enough? How many patients you needed depends on what you found. Archives of Internal Medicine 1985;145(4): 709–12. Glanville 2006 Glanville JM, Lefebvre C, Miles JN, Camosso-Stefinovic J. How to identify randomized controlled trials in MEDLINE: ten years on. Journal of the Medical Library Association 2006; 94(2):130–6. Hattenhauer 1997 Hattenhauer MG, Leavitt JA, Hodge DO, Grill R, Gray DT. Incidence of nonarteritic anterior ischemic optic neuropathy. American Journal of Ophthalmology 1997;123 (1):103–7. Hayreh 1975 Hayreh SS. Anterior ischemic optic neuropathy. New York: Springer Verlag NY Inc, 1975. Hayreh 1981 Hayreh SS. Anterior ischemic optic neuropathy. Archives of Neurology 1981;38(11):675–8. Hayreh 1990 Hayreh SS. Anterior ischemic optic neuropathy: differentiation of arteritic from non-arteritic type and its management. Eye 1990;4(Pt 1):25–41. Higgins 2011 Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. Johnson 1994 Johnson LN, Arnold AC. Incidence of non-arteritic anterior ischemic optic neuropathy: population based study in the state of Missouri and Los Angeles County, California. Journal of Neuro-Ophthalmology 1994;14(1):38–44. RevMan 2014 [Computer program] The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

References to other published versions of this review Dickersin 1999 Dickersin K, Manheimer E. Surgery for nonarteritic anterior ischemic optic neuropathy. Cochrane Database of Systematic Reviews 1999, Issue 2. [DOI: 10.1002/ 14651858.CD001538]


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Dickersin 2006 Dickersin K, Manheimer E, Li T. Surgery for nonarteritic anterior ischemic optic neuropathy. Cochrane Database of Systematic Reviews 2006, Issue 1. [DOI: 10.1002/ 14651858.CD001538.pub2] Dickersin 2012 Dickersin K, Manheimer E, Li T. Surgery for nonarteritic anterior ischemic optic neuropathy. Cochrane Database of Systematic Reviews 2012, Issue 1. [DOI: 10.1002/ 14651858.CD001538.pub3] ∗ Indicates the major publication for the study


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CHARACTERISTICS OF STUDIES

Characteristics of included studies [ordered by study ID] IONDT Methods

Multicenter randomized controlled trial

Participants

Participants: 258 men and women, aged 50 years or older, diagnosed with NAION Eligibility criteria: sudden onset of subjective symptoms of loss of vision (with duration of symptoms less than 14 days at the baseline examination); a best-corrected visual acuity in the affected eye of 20/64 or worse; a relative afferent pupillary defect (bilateral disease excepted); optic disc edema; and visual field defects consistent with optic neuropathy Medical exclusion criteria: conditions likely to exclude NAION as the primary diagnosis; conditions putting the participant at increased surgical risk; conditions indicating a nonischemic etiology; and ophthalmologic conditions that might impair a measurement of change in visual acuity or visual field

Interventions

1. Optic nerve decompression surgery and careful follow-up 2. Careful follow-up alone (without treatment) Careful follow-up included an ophthalmologic examination at each visit and visual field testing at 12 months and as needed

Outcomes

Primary outcome: gain or loss of 3 or more lines of visual acuity on the New York Lighthouse Chart at six months after randomization, as measured by a technician masked to treatment assignment; analyzed on an intention-to-treat basis Secondary outcomes: additional follow-up for visual acuity at 12, 18, and 24 months, visual field change at 12 months, and new cases of NAION in the fellow eye

Notes Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

“Patients had an equal probability of being assigned to either ONDS or careful followup. Randomization was stratified by clinic, using permuted blocks of size two or four, always starting with block size of two, with the size randomly selected thereafter.” (IONDT 1998, page 283)

Allocation concealment (selection bias)

“The patient became officially enrolled in the trial at the time the clinic coordinator or study neuro-ophthalmologist telephoned the coordinating center and received the randomization assignment.” (IONDT 1995, page 626)

Low risk


12

IONDT

(Continued)

Masking (performance bias and detection Low risk bias) Visual acuity outcomes

Measurements of visual acuity were performed according to a uniform protocol, by a certified technician masked to the treatment received. Although observers were unmasked at one-week and one-month follow-up visits due to the physical effects of surgery, these follow-up measurements were not part of the visual acuity outcome analysis

Masking (performance bias and detection Low risk bias) Visual field outcomes

Measurements of visual fields were performed by certified Visual Field Technicians masked to treatment assignment, using automated static perimetry with program 24-2 and size III stimulus on the Humphrey Field Analyzer

Incomplete outcome data (attrition bias) Visual acuity outcomes

High risk

Participants were analyzed as part of the treatment group to which they were assigned; however, participants with missing baseline or follow-up data were excluded from the analyses. Three (1%) participants did not have baseline data, 12 (5%) participants did not complete six-months follow-up, and 84 (33%) participants did not complete 24months follow-up

Incomplete outcome data (attrition bias) Visual field outcomes

High risk

Visual fields were scored for reliability and unreliable visual fields were excluded from the analysis. Further, “two patients with reliable 12-month visual fields underwent surgery instead of careful follow-up and were analyzed as part of the surgical group.”

Selective reporting (reporting bias)

Low risk

All outcomes specified in the methods paper and in the protocol were reported. Unadjusted risk ratios and adjusted odds ratios were presented for the study outcomes

Other bias

Low risk

The study was stopped early for futility. It was reported that continued enrollment would not statistically affect the results in favor of surgery

NAION: non-arteritic ischemic optic neuropathy


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Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Glaser 1994

Uncontrolled case series Participants: 21 people with NAION Intervention: optic nerve decompression surgery Outcome: visual acuity

Kelman 1991

Uncontrolled case series Participants: 7 people with NAION Intervention: optic nerve decompression surgery Outcome: visual acuity and visual field

Plotnik 1993

Uncontrolled case series Participants: 31 people with various types of optic nerve dysfunction Intervention: optic nerve decompression surgery Outcome: postoperative complications of decompression surgery

Sergott 1989

Trial used concurrent, non-randomized controls Participants: 14 people with progressive NAION; 12 control participants with similar entry-level visual acuity and field loss Interventions: optic nerve decompression surgery for experimental group; usual care for concurrent non-randomized controls Outcome: visual acuity and visual field

Spoor 1991

Uncontrolled case series Participants: four people with NAION Intervention: optic nerve decompression surgery Outcome: visual function

Spoor 1993

Uncontrolled case series Participants: 23 people with progressive NAION; 15 people with nonprogressive NAION Intervention: optic nerve sheath decompression surgery Outcomes: visual acuity, visual field

Yee 1994

Trial used concurrent, non-randomized controls Participants: 91 people with NAION Intervention: comparison of affected eyes treated with surgery with affected eyes that did not have surgery Outcome: visual acuity

NAION: non-arteritic ischemic optic neuropathy


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DATA AND ANALYSES

Comparison 1. Optic nerve decompression surgery and careful follow-up versus careful follow-up alone

Outcome or subgroup title 1 Improvement of 3 or more lines of vision at six months 2 Improvement of 3 or more lines of vision at 24 months

No. of studies

No. of participants

Statistical method

Effect size

1

Risk Ratio (M-H, Fixed, 95% CI)

Totals not selected

1

Risk Ratio (M-H, Fixed, 95% CI)

Totals not selected

Analysis 1.1. Comparison 1 Optic nerve decompression surgery and careful follow-up versus careful followup alone, Outcome 1 Improvement of 3 or more lines of vision at six months. Review:

Surgery for nonarteritic anterior ischemic optic neuropathy

Comparison: 1 Optic nerve decompression surgery and careful follow-up versus careful follow-up alone Outcome: 1 Improvement of 3 or more lines of vision at six months

Study or subgroup

IONDT

Decompression

Careful follow-up

n/N

n/N

39/122

52/122

Risk Ratio

Risk Ratio

M-H,Fixed,95% CI

M-H,Fixed,95% CI 0.75 [ 0.54, 1.04 ]

0.2

0.5

Careful follow-up


1

2

5

Decompression

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Analysis 1.2. Comparison 1 Optic nerve decompression surgery and careful follow-up versus careful followup alone, Outcome 2 Improvement of 3 or more lines of vision at 24 months. Review:

Surgery for nonarteritic anterior ischemic optic neuropathy

Comparison: 1 Optic nerve decompression surgery and careful follow-up versus careful follow-up alone Outcome: 2 Improvement of 3 or more lines of vision at 24 months

Study or subgroup

Decompression

Careful follow-up

n/N

n/N

25/85

27/87

IONDT

Risk Ratio

Risk Ratio

M-H,Fixed,95% CI

M-H,Fixed,95% CI 0.95 [ 0.60, 1.49 ]

0.2

0.5

1

Careful follow-up

2

5

Decompression

ADDITIONAL TABLES Table 1. Comparison of participants with data at baseline and at 24 months in the IONDT

Variable

All randomized

24-month cohort

Careful follow- Surgery up (n = 127) (n = 131)

P*

Careful follow-up (n = 89)

Surgery (n = 85)

P*

Visual acuity, mean ± SD Baseline, logMAR

1.31 ± 0.61

1.23 ± 0.60

0.26

1.25 ± 0.61

1.16 ± 0.59

0.33

On chart, %

80.9

80.3

0.90

83.2

83.5

0.95

Change at 2.4 ± 4.8 3 months in lines improved

1.3 ± 5.4

0.09

2.2 ± 5.1

1.3 ± 5.6

0.28

Change at 2.0 ± 5.1 6 months in lines improved

1.2 ± 6.0

0.29

1.6 ± 5.6

1.1 ± 6.0

0.56

Change at 12 1.9 ± 5.6 months in lines improved

1.6 ± 5.8

0.70

1.7 ± 6.0

1.7 ± 5.8

0.99


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Table 1. Comparison of participants with data at baseline and at 24 months in the IONDT

(Continued)


1.4 ± 6.0

0.88

1.1 ± 6.0

1.3 ± 6.1

0.90


1.1 ± 6.4

0.92

1.0 ± 6.0

1.1 ± 6.4

0.92

Age, years, mean 68.2 ± 8.4 ± SD

67.9 ± 8.6

0.81

68.1 ± 8.0

67.6 ± 8.0

0.65

Age, < 65 years, 34.4 %

34.7

0.96

32.6

35.3

0.71

Sex, % men

54.2

56.7

0.69

58.4

58.8

0.96

Late entry, %

11.5

23.6

0.01

14.6

24.7

0.09

Diabetes, %

32.8

20.5

0.03

32.6

17.7

0.02

Hypertension, %

52.7

48.8

0.54

52.8

49.4

0.65

Cataract, % of 41.2 study eyes

34.7

0.28

38.2

28.2

0.16

Previous cataract 13.7 surgery, %

13.4

0.93

14.6

14.1

0.93

Previous 13.7 NAION in nonstudy eye, %

18.9

0.26

15.7

15.3

0.94

Baseline characteristics

*P values from t test for means and x2 test for percentages NAION: nonarteritic anterior ischemic optic neuropathy SD: standard deviation

Table 2. Changes in superior field defects from baseline to 12-months follow-up

Improveda

Surgery participants (n = 85)

Careful follow-up participants (n = Score test for trends of odds 94)

7 (8.2%)

5 (5.3%)


χ 2 = 0.26 P = 0.61

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Table 2. Changes in superior field defects from baseline to 12-months follow-up

Unchangedb

70 (82.4%)

80 (85.1%)

Worsec

8 (9.4%)

9 (9.6%)

(Continued)

a Improvement

in the superior field was defined as a change in classification from (1) an arcuate defect to normal (defined as no defect in superior region), or (2) an altitudinal defect to an arcuate defect or normal. b Unchanged in the superior field was defined as (1) normal at both baseline and follow-up, or (2) defect unchanged from baseline to follow-up. c Worsening in the superior field was defined as a change in classification from (1) an arcuate to an altitudinal defect, or (2) a normal to an arcuate or altitudinal defect.

Table 3. Changes in inferior field defects from baseline to 12-months follow-up



Improveda

8 (9.5%)

7 (7.4%)

Unchangedb

71 (84.5%)

81 (86.2%)

Worsec

5 (6.0%)

6 (6.4%)

χ 2 = 0.19 P = 0.66

a Improvement

in the inferior field was defined as a change in classification from (1) an arcuate defect to normal, or (2) an altitudinal defect to an arcuate defect or normal. b Unchanged in the inferior field was defined as (1) normal at both baseline and follow-up, or (2) defect unchanged from baseline to follow-up. c Worsening in the inferior field was defined as a change in classification from (1) an arcuate to an altitudinal defect, or (2) a normal to an arcuate or altitudinal defect.

Table 4. Changes in central field defects from baseline to 12-months follow-up



Improveda

20 (23.5%)

17 (18.1%)

Unchangedb

56 (65.9%)

69 (73.4%)

Worsec

9 (10.6%)

8 (8.5%)

χ 2 = 0.17 P = 0.68

a

Improvement in the central field was defined as a change from (1) a central to a paracentral scotoma or a normal region, or (2) a paracentral scotoma to a normal region. b Unchanged in the central field was defined as (1) normal at both baseline and follow-up, or (2) defect unchanged from baseline to follow-up. c Worsening in the inferior field was defined as a change from (1) a paracentral to central scotoma or (2) a normal region to either paracentral or central scotoma.


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APPENDICES Appendix 1. CENTRAL search strategy #1 MeSH descriptor: [Optic Neuropathy, Ischemic] explode all trees #2 MeSH descriptor: [Optic Nerve Diseases] explode all trees #3 MeSH descriptor: [Optic Nerve] explode all trees #4 optic* near (nerve* or neuropath*) #5 isch*emic #6 non next arter* or (nonarter* or NAION) #7 #2 or #3 or #4 #8 #5 or #6 #9 #7 and #8 #10 #1 or #9 #11 MeSH descriptor: [Therapeutics] explode all trees #12 MeSH descriptor: [Surgical Procedures, Operative] explode all trees #13 MeSH descriptor: [General Surgery] explode all trees #14 MeSH descriptor: [Decompression] explode all trees #15 therap* or treat* or decompress* or fenestrat* or manag* or surg* #16 #11 or #12 or #13 or #14 or #15 #17 #10 and #16

Appendix 2. MEDLINE (OvidSP) search strategy 1. randomized controlled trial.pt. 2. controlled clinical trial.pt. 3. (randomized or randomised).ab,ti. 4. placebo.ab,ti. 5. drug therapy.fs. 6. randomly.ab,ti. 7. trial.ab,ti. 8. groups.ab,ti. 9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 10. exp animals/ not humans.sh. 11. 9 not 10 12. exp optic neuropathy ischemic/ 13. exp optic nerve diseases/ 14. exp optic nerve/ 15. ((nerve* or neuropath*) adj3 optic*).tw. 16. isch?emic*.tw. 17. ((non adj1 arter*) or nonarter* or naion).tw. 18. 13 or 14 or 15 19. 16 or 17 20. 18 and 19 21. 12 or 20 22. exp therapeutics/ 23. exp surgical procedures operative/ 24. exp general surgery/ 25. exp decompression/ 26. (therap* or treat* or decompress* or fenestrat* or manag* or surg*).tw. 27. 22 or 23 or 24 or 25 or 26 28. 21 and 27 29. 11 and 28 Surgery for nonarteritic anterior ischemic optic neuropathy (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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The search filter for trials at the beginning of the MEDLINE strategy is from the published paper by Glanville (Glanville 2006).

Appendix 3. EMBASE.com search strategy #1 ’randomized controlled trial’/exp OR ’randomized controlled trial’ #2 ’randomization’/exp #3 ’double blind procedure’/exp #4 ’single blind procedure’/exp #5 random*:ab,ti #6 #1 OR #2 OR #3 OR #4 OR #5 #7 ’animal’/exp OR ’animal experiment’/exp #8 ’human’/exp #9 #7 AND #8 #10 #7 NOT #9 #11 #6 NOT #10 #12 ’clinical trial’/exp #13 (clin* NEAR/3 trial*):ab,ti #14 ((singl* OR doubl* OR trebl* OR tripl*) NEAR/3 (blind* OR mask*)):ab,ti #15 ’placebo’/exp #16 placebo*:ab,ti #17 random*:ab,ti #18 ’experimental design’/exp #19 ’crossover procedure’/exp #20 ’control group’/exp #21 ’latin square design’/exp #22 #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 #23 #22 NOT #10 #24 #23 NOT #11 #25 ’comparative study’/exp #26 ’evaluation’/exp #27 ’prospective study’/exp #28 control*:ab,ti OR prospectiv*:ab,ti OR volunteer*:ab,ti #29 #25 OR #26 OR #27 OR #28 #30 #29 NOT #10 #31 #30 NOT (#11 OR #23) #32 #11 OR #24 OR #31 #33 ’ischemic optic neuropathy’/exp #34 ’optic nerve disease’/exp #35 ’optic nerve’/exp #36 ((nerve* OR neuropath*) NEAR/3 optic*):ti,ab #37 isch*emic*:ti,ab #38 (non NEAR/1 arter*):ti,ab OR nonarter*:ti,ab OR naion:ti,ab #39 #34 OR #35 OR #36 #40 #37 OR #38 #41 #39 AND #40 #42 #33 OR #41 #43 ’therapy’/exp #44 ’eye surgery’/exp #45 ’decompression’/exp #46 therap*:ti,ab OR treat*:ti,ab OR decompress*:ti,ab OR fenestrat*:ti,ab OR manag*:ti,ab OR surg*:ti,ab #47 #43 OR #44 OR #45 OR #46 #48 #42 AND #47 Surgery for nonarteritic anterior ischemic optic neuropathy (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

20

#49 #32 AND #48

Appendix 4. PubMed search strategy #1 ((randomized controlled trial[pt]) OR (controlled clinical trial[pt]) OR (randomised[tiab] OR randomized[tiab]) OR (placebo[tiab]) OR (drug therapy[sh]) OR (randomly[tiab]) OR (trial[tiab]) OR (groups[tiab])) NOT (animals[mh] NOT humans[mh]) #2 optic*[tw] AND (nerve*[tw] OR neuropath*[tw]) NOT Medline[sb] #3 (ischemic[tw] OR ischaemic[tw]) NOT Medline[sb] #4 (non arter*[tw] OR nonarter*[tw] OR NAION[tw]) NOT Medline[sb] #5 #3 OR #4 #6 #2 AND #5 #7 (theap*[tw] OR treat*[tw] OR decompress*[tw] OR fenestrat*[tw] OR manag*[tw] OR surg*[tw]) NOT Medline[sb] #8 #6 AND #7 #9 #1 AND #8

Appendix 5. metaRegister of Controlled Trials search strategy (optic neuropathy OR NAION) AND surgery

Appendix 6. ClinicalTrials.gov search strategy (optic neuropathy OR NAION) AND surgery

Appendix 7. ICTRP search strategy optic neuropathy AND surgery OR NAION AND surgery

WHAT’S NEW Last assessed as up-to-date: 23 October 2014.

Date

Event

Description

28 January 2015

New search has been performed

Issue 3, 2015: Electronic searches updated; no new studies identified for inclusion. The review also has been updated using new Cochrane reporting guidelines

28 January 2015

New citation required but conclusions have not changed Issue 3, 2015: Two references to already included study (IONDT) added.


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HISTORY Review first published: Issue 2, 1999

Date

Event

Description

7 December 2011

New search has been performed

Issue 1, 2012: Electronic searches were updated but no new studies were identified for inclusion in this update. The review also has been updated using new Cochrane methodology including a risk of bias table being completed for the included study

7 December 2011

New citation required but conclusions have not Issue 1, 2012: New results for already included study ( changed IONDT) added.

16 October 2008

Amended

Converted to new review format.

25 August 2005

New citation required and conclusions have changed

Substantive amendment

CONTRIBUTIONS OF AUTHORS KD provided oversight of the review, reviewed reports potentially eligible for the review, wrote some sections of the review and edited all versions of the review. TL performed the initial examination of the search results in 2005 and forward. She also extracted data for the review updates and added these to the review.

DECLARATIONS OF INTEREST Kay Dickersin was principal investigator of the Coordinating Center for the Ischemic Optic Neuropathy Decompression Trial and a member of the writing team for most IONDT publications.

SOURCES OF SUPPORT Internal sources • No sources of support supplied


22

External sources • National Eye Institute, National Institutes of Health, USA. KD and TL supported by the Cochrane Eyes and Vision Group US Project, funded by Grant 1 U01 EY020522 • National Institute for Health Research (NIHR), UK. • Richard Wormald, Co-ordinating Editor for the Cochrane Eyes and Vision Group (CEVG) acknowledges financial support for his CEVG research sessions from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology. • The NIHR also funds the CEVG Editorial Base in London. The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS, or the Department of Health.

INDEX TERMS Medical Subject Headings (MeSH) Early Termination of Clinical Trials; Optic Neuropathy, Ischemic [∗ surgery]; Postoperative Complications; Randomized Controlled Trials as Topic; Treatment Failure; Visual Acuity

MeSH check words Humans


23

A new characterization for nonarteritic anterior ischemic optic neuropathy.

Choroidal thickness in nonarteritic anterior ischemic optic neuropathy.

Nonarteritic Anterior Ischemic Optic Neuropathy Induced Retinal Folds and Deformations.

Choroidal thickness in nonarteritic anterior ischemic optic neuropathy.

Peripapillary Pachychoroid in Nonarteritic Anterior Ischemic Optic Neuropathy.

Systemic corticosteroids in nonarteritic ischemic optic neuropathy.

Analysis of Fundus Photography and Fluorescein Angiography in Nonarteritic Anterior Ischemic Optic Neuropathy and Optic Neuritis.

Dendrimers Target the Ischemic Lesion in Rodent and Primate Models of Nonarteritic Anterior Ischemic Optic Neuropathy.

Clinical Efficacy Observation of Acupuncture Treatment for Nonarteritic Anterior Ischemic Optic Neuropathy.

Neutrophil to Lymphocyte Ratio in Patients with Nonarteritic Anterior Ischemic Optic Neuropathy.

Bilateral Simultaneous Nonarteritic Anterior Ischaemic Optic Neuropathy: Case Report.

Optic neuritis or anterior ischemic optic neuropathy?

Risk of Nonarteritic Anterior Ischemic Optic Neuropathy Following End-Stage Renal Disease.

Acute nonarteritic anterior ischemic optic neuropathy and exposure to phosphodiesterase type 5 inhibitors.

Bilateral simultaneous nonarteritic anterior ischemic optic neuropathy in a patient with alcoholic liver disease.

Central corneal thickness measurements in nonarteritic anterior ischemic optic neuropathy patients: a controlled study.

Optic nerve sheath decompression for nonarteritic ischemic optic neuropathy improves multiple visual function measurements.

Comparison of the Deep Optic Nerve Head Structure between Normal-Tension Glaucoma and Nonarteritic Anterior Ischemic Optic Neuropathy.

Retinal Vessel Density in Optical Coherence Tomography Angiography in Optic Atrophy after Nonarteritic Anterior Ischemic Optic Neuropathy.

Familial anterior ischemic optic neuropathy and papillophlebitis.

[Atypical genesis of anterior ischemic optic neuropathy].

Anterior ischemic optic neuropathy in association with optic nervehead drusen.

Intravitreal dexamethasone implant [Ozurdex] for the treatment of nonarteritic anterior ischaemic optic neuropathy.

Sustained neuroprotection from a single intravitreal injection of PGJ₂ in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy.