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Prospective analysis of macular and optic disc changes after non-arteritic anterior ischemic optic neuropathy
Journal français d’ophtalmologie (2020) 43, 35—42
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ORIGINAL ARTICLE
Prospective analysis of macular and optic disc changes after non-arteritic anterior ischemic optic neuropathy Analyse prospective des modifications maculaires et des disques optiques après une neuropathie optique ischémique antérieure non-artéritique I. García-Basterra a,b,∗, A. García-Ben c, F. Ríus-Díaz d, A. González-Gómez a, T.R. Hedges e, L.N. Vuong e, J.M. García-Campos a,f a
Department of Ophthalmology, University Hospital Virgen de la Victoria, Málaga, Spain Department of Ophthalmology, Hospital Costa del Sol, Marbella, Spain c Department of Ophthalmology, University Hospital Santiago de Compostela, Spain d Department of Preventive Medicine, Statistics and Public Health, University of Málaga, Spain e The New England Eye Center, Tufts Medical Center, Tufts University, Boston, USA f Department of Ophthalmology, Centro de Investigaciones Médico-Sanitarias, University of Málaga, Spain b
Received 15 December 2018; accepted 4 March 2019 Available online 6 November 2019
KEYWORDS Ischemic optic neuropathy; Optical coherence tomography
∗
Summary Purpose. — To prospectively analyse macular and optic disc changes after the occurrence of non-arteritic anterior ischemic optic neuropathy (NAION) and study possible predictors of final visual outcome. Methods. — Patients with NAION underwent a complete ophthalmic examination, including spectral-domain optical coherence tomography of the macula and optic nerve head. The examination was repeated 1, 3, 6, 9 and 12 months after onset. Final visual prognosis was evaluated by visual field (VF) and best-corrected visual acuity (BCVA) at the final visit. Data within the NAION group were analysed over the course of the disease and compared to a disease-free control group at each visit. Results. — Twenty-two eyes with NAION and 43 eyes from a control group were included. The retinal nerve fiber layer (RNFL) was significantly thicker in NAION eyes than controls at
Corresponding author at: Department of Ophthalmology, Hospital Virgen de la Victoria, Campus Teatinos, S/N, Málaga, 29010, Spain. E-mail address: [email protected] (I. García-Basterra).
https://doi.org/10.1016/j.jfo.2019.03.034 0181-5512/© 2019 Elsevier Masson SAS. All rights reserved.
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I. García-Basterra et al. presentation (P = 0.00), and significantly decreased during the next 3 months after presentation (P = 0.02). The ganglion cell + inner plexiform layer (GCIPL) was thinner in the NAION group throughout the course of the disease (all P < 0.05). Although the acute NAION eyes had significantly lower cup/disc ratios and higher neuroretinal and disc sizes (all P = 0.00), there were no significant differences between groups from the third month onwards (all P > 0.05). The best predictors of BCVA and VF were GCIPL at 3 months of follow-up (r2 = 0.32; P = 0.03) and RNFL at 6 months of follow-up (r2 = 0.41; P = 0.01) respectively. Conclusions. — RNFL and optic disc changes occur during the first 3 months after the onset of NAION, whereas GCIPL is affected soon after the onset of symptoms. GCIPL and RNFL are useful predictors of final visual outcome. © 2019 Elsevier Masson SAS. All rights reserved.
MOTS CLÉS Neuropathie optique ischémique ; Tomographie par cohérence optique
Résumé Objectif. — Analyser prospectivement les modifications maculaires et papillaires après survenue d’une neuropathie optique ischémique antérieure aiguë (NOIAN) et étudier les facteurs prédictifs du résultat visuel final. Méthodes. — Les patients atteints de NOIAN ont subi un examen ophtalmique complet, comprenant une tomographie par cohérence optique dans le domaine spectral de la macula et de la tête du nerf optique. L’examen est répété 1,3,6,9 et 12 mois après le début. Le pronostic visuel final a été évalué avec le champ visuel (CV) et la meilleure acuité visuelle corrigée (MAVC) lors de la visite finale. Les données du groupe NOIAN ont été analysées au cours de l’évolution de la maladie et comparées à un groupe témoin indemne de la maladie à chaque examen. Résultats. — Vingt-deux yeux atteints de NOIAN et 43 yeux d’un groupe témoin ont été inclus. La couche de fibres nerveuses rétiniennes (CFNR) était significativement plus épaisse dans les yeux NOIAN que chez les témoins lors de la présentation (p = 0,00) et avait diminué de manière significative au cours des trois mois suivant la présentation (p = 0,02). Les cellules ganglionnaires et la couche plexiforme interne (CGCPI) étaient plus minces dans le groupe NOIAN pendant toute la durée de la maladie (p < 0,05). Bien que les yeux avec NOIAN aiguës avaient des ratio C/D significativement plus faibles et des tailles de disque et d’anneau neurorétinien plus élevées (p = 0,00), il n’y a pas eu de différence significative entre les groupes jusqu’au troisième mois (p > 0,05). Les meilleurs prédicteurs de MAVC et CV étaient la CGCPI à 3 mois (r2 = 0,32; p = 0,03) et la CFNR à 6 mois (r2 = 0,41; p = 0,01). Conclusions. — Les modifications de la CFNR et du disque optique se produisent au cours des 3 premiers mois suivant l’apparition de la NOIAN, alors que la CGCPI est affectée peu de temps après l’apparition des symptômes. CGCPI et CFNR sont les meilleurs prédicteurs du résultat visuel final. © 2019 Elsevier Masson SAS. Tous droits r´ eserv´ es.
Introduction Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute optic neuropathy in people over the age of 50. Although its physiopathogenesis is not entirely known, it is assumed to be caused by vascular insufficiency of the optic disc that eventually provokes optic nerve damage [1]. The acute optic nerve injury due to ischemia typically entails significant visual field defects and reduced visual acuity, which tend to be permanent and cause huge impairment in activities of daily living. Optical coherence tomography (OCT) can provide images of the retina and optic nerve that closely resemble histological samples. In NAION, OCT mainly has been used to diagnose and quantify optic disc edema and to monitor peripapillary
retinal nerve fiber layer loss [2—5]. Recent advances in segmentation algorithms have made it possible to visualise and measure individual retinal layers and accurately locate the damage. While most OCT studies of NAION cases have performed retrospective analysis of the optic disc and peripapillary retina both in the acute and chronic stages, few studies have focused on analysing macular and optic nerve changes over the course of the disease. Prospective quantitative and qualitative analysis of optic nerve and macula parameters may help in understanding the pathophysiology of NAION and other optic nerve diseases. The objective of this work is to analyse OCT macular and disc parameters in patients with acute NAION over 1year of follow-up and to compare the measurements with a
Prospective tomographic changes after NAION free-disease group. These variables are also correlated with final visual prognosis, measured as visual acuity and mean deviation on visual field at 12 months of follow-up.
Methods In this prospective observational study, 21 patients with NAION (22 eyes) and a control group composed of 43 patients (43 eyes) were evaluated in University Hospital Virgen de la Victoria from March 2015 to September 2018. The ethics committee of Malaga approved the study according to all federal laws in Spain and the Declaration of Helsinki. Written informed consent was obtained from all subjects. NAION was defined as a sudden and painless visual loss with optic disc swelling and sectoral visual field loss. To rule out anterior ischemic optic neuropathy, all patients were asked for the presence of any symptoms of giant cell arteritis. An examination of the temporal artery and a determination of C reactive protein and erythrocyte sedimentation rate were also performed to completely ruled out this disease. All patients recruited followed a clinical course consistent with ischemic optic neuropathy, with a full resolution of the optic disc edema within 2 months of follow-up. Control subjects were randomly recruited from patients attended for other reasons than retina, vitreous or other optic nerve diseases. Subjects with previous ocular surgery (except cataract surgery), media opacities, coexistence of neurological or systemic diseases or refractive error greater than minus 6 diopters were excluded. All subjects underwent an ophthalmologic examination that included a slit-lamp examination, ophthalmoscopy and tonometry. The best-corrected visual acuity (BCVA) was measured using a Snellen chart at 6 meters. Axial length was measured using IOL Master (Carl Zeiss Meditec, Dublin, CA) and refractometry using an automated refractometer (RM-8900; Topcon, Tokyo, Japan). Automatic visual field (VF) were tested with SITA FAST 30-2 (Swedish Interactive Thresholding Algorithm; Humphrey, Carl Zeiss Meditec, Dublin, CA, USA). Automated VF was performed at the first visit and 12 months after the acute episode on every patient, and the mean deviation (MD) was used for statistical analysis. OCT scanning was performed after pupil dilation with tropicamide 1% (Alcon Cusi, Barcelona, Spain) using Cirrus-OCT (Carl Zeiss Meditec, Dublin, CA, USA) and enhanced-depth imaging technique. Ophthalmic and OCT examinations were repeated 1, 3, 6, 9 and 12 months after the acute episode. Each eye was scanned using an optic disc cube (200 × 200 line scans) protocol and a macular cube (512 × 128 line scans). The scanned areas (6 × 6 mm) were centered on the nerve for retinal nerve fiber layer analysis (RNFL) and on the fovea for ganglion cell-inner plexiform layer (GCIPL) and average macular thickness (MT) analyses. Automatic segmentation algorithms were used to determine the RNFL and GCIPL sectoral thickness (m). The average thickness of the MT, RNFL and GCIPL were automatically obtained by the software and used for analysis. Only scans with uniform brightness and signal strength equal to or greater than 6 in intensity were included in the study. All statistical analyses were performed via Microsoft Excel 2007 (Microsoft Corp., Redmond, WA, USA) and SPSS statistics (IBM-SPSS, Chicago, IL, USA). In the study group,
37 the affected eye was included in the study, whereas for the control group only the right eyes were included. The left eye was only scanned when a low quality image was obtained from the right eye. Sample size was calculated using standard deviation from earlier studies about RNFL thickness [2,3,5—7] (the main variable studied in NAION). OCT measurements of the NAION eyes were evaluated over the course of the disease and compared with the data obtained from the free-disease control group. Chi-Square, T Student and Mann—Whitney U test contrasts for independent samples, considering homoscedasticity, were used to detect differences between groups, linear regression to quantify the relation among parameters and repeated measures general linear model (one-way ANOVA with repeated measures) to analyse changes over the 1 year of follow up. Univariate analyses were also used to look for associations between OCT parameters and final BCVA and MD. R Square, Pearson correlation coefficient, unstandardized coefficient B, test of between-subjects and within-subjects effects with Greenhouse-Geisser and Bonferroni’s post-test corrections, pairwise comparisons and 95% confidence intervals (95% CIs) were presented. All P values were based on 2-sided tests and were considered statistically significant when the values were less than 0.05.
Results Nineteen eyes with NAION and 43 disease-free control eyes were studied. Three patients with NAION were excluded due to coexistence of other neurological or retinal disorders. One patient included his two eyes as acute NAION, one patient had a previous documented episode of NAION in the fellow eye, two patients had optic nerve or visual field findings consistent with previous ischemic damage on their contralateral eyes and 1 patient had only one eye due to an early traumatic injury in the fellow eye. Table 1 provides a distribution of clinical and demographic characteristics of both groups. All individuals included were Caucasians. Except for BCVA (P = 0.00), no statistically significant differences were observed between groups.
Retinal Nerve Fiber Layer Fig. 1 shows the profile plot of average retinal nerve fiber layer (RNFL) thickness one year after initial evaluation. Compared to controls, mean RNFL was significantly thicker in eyes affected with acute NAION (203.63 ± 81.41 m vs. 88.86 ± 10.74 m; P = 0.00) and significantly thinner from the third month of follow-up to the end of the study (59.50 ± 11.52 m vs. 88.86 ± 10.74 m; all P values < 0.05). Repeated measures general linear model showed statistically significant changes of mean RNFL values over time within the group of NAION (Greenhouse-Geisser, F = 16.68; P = 0.02). There was no statistically significant difference in average RNFL between NAION and control group (test of between-subjects P = 0.71). Pairwise comparisons revealed significant differences between initial RNFL and 1 month RNFL and the rest of RNFL values (P values < 0.05). From the 3rd to the 12th month,
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Table 1 Demographic and Clinical Characteristics of Nonarteritic Ischemic Optic Neuropathy Group and Disease-Free Control Group. Variable
NAION (n = 19)
Controls (n = 43)
P value
Age (years) Gender (male/female) BCVA (LogMAR) IOP (mmHg) Axial length (mm) Refractive Error (diopters) Hypertension (Yes/No) Diabetes (type I/type II/No diabetes) Dyslipidemia (Yes/No) Smoking (Yes/No) OSAS (Yes/No)
63.89 ± 12.47 14/5 0.32 ± 0.39 15.33 ± 4.24 22.99 ± 1.18 0.66 ± 2.54 13/6 1/3/15 12/7 4/15 0/19
62.21 ± 11.25 22/21 0.99 ± 0.05 14.29 ± 1.96 23.30 ± 0.82 0.84 ± 1.77 20/23 0/3/40 16/27 7/36 3/40
0.60 0.16 0.00 0.60 0,09 0.77 0.17 0.16 0.10 0.72 0.55
NAION: Nonarteritic Ischemic Optic Neuropathy; BCVA: Best Corrected Visual Acuity; IOP: Intraocular Pressure; OSAS: Obstructive Sleep Apnea Syndrome. Data are presented as mean ± standard deviation. A value of P < 0.05 was considered statistically significant.
neuroretinal rime areas decreased abruptly. At final visit, although average C/D ratios were smaller and NRA bigger in NAION eyes compared to controls, there were no statistically significant differences between groups (P < 0.05). Repeated measures general linear model revealed statistically significant changes of average and vertical CD ratios and DS (Greenhouse—Geisser F = 4.54, F = 5.69, F = 5.48; all P < 0.05), whereas there were no significant changes of NRA over time (P = 0.09). Pairwise comparisons showed that CD changes occurred during three months after presentation; meanwhile changes in DS and NRA were limited to the first month of follow-up.
Ganglion Cell Complex and Average Macular Thickness
Figure 1. Retinal nerve fiber layer progression over 1 year of follow-up after non-arteritic ischemic optic neuropathy (NAION). Asterisks show significant differences between groups at each visit. (T-Student and U de Mann—Whitney) A value of P < 0.05 was considered statistically significant.
there were no statistically significant changes of RNFL values (P values > 0.05).
Optic disc Fig. 2 shows the profile plot of average cup-disc (C/D) ratio, vertical C/D ratio, disc size (DS) and neuroretinal rim area (NRA) over the course of the disease in the NAION group. Compared to controls, both average and vertical C/D ratios were significantly smaller in eyes affected with acute NAION (all P values < 0.05). In contrast, DS and NRA were significantly larger in acute NAION eyes than controls (all P values < 0.05). Over time, C/D ratios progressively increased, whereas disc size and
Fig. 3 shows the profile plots of average macular thicknesses (MT) and mean and sectoral ganglion cell-inner plexiform layer thicknesses (GCIPL) over the 1-year followup. GCIPL thicknesses were significantly thinner in NAION group all over the 1-year of follow-up (all P values < 0.05). Except for nasal GCIPL thicknesses, which progressively decreased over time, all sectoral GCIPL values increased during the first month of follow up and eventually decreased over time. Except for supero-nasal GCIPL thickness, all the thicknesses were significantly different between groups (all P values < 0.05). There were no significant changes of average and sectoral GCIPL thicknesses over time (test of within-subjects: all P values > 0.05). Average macular thicknesses (MT) were significantly thinner in NAION eyes compared to controls at 3, 6, 9 and 12 months of follow-up (all P < 0.05). There were no statistically significant differences between MT at initial and 1-month follow-up between groups (306.57 m and 280.43 m vs. 278.72 m; P > 0.05). The general linear model showed statistically significant changes of average MT over follow-up (P = 0.00). Pairwise comparisons showed that MT changes over time occurred during the first 2 months (P < 0.05).
Prospective tomographic changes after NAION
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Figure 2. Optic disc changes over 1 year of follow-up after non-arteritic ischemic optic neuropathy (NAION). Asterisks show significant differences between groups at each visit. (T-Student and U de Mann—Whitney) A value of P < 0.05 was considered statistically significant.
Visual Prognosis In the NAION group the mean BCVA at first and final visit were 0.32 ± 0.39 and 0.28 ± 0.30 (P = 0.63). BCVA improved in 7 subjects (36.8%), got worse in 6 (31.6%) and 6 did not significantly change at final visit (31.6%). The average MD at first and final visit were − 24.34 ± 5.38 dB and − 23.39 ± 7.10 dB (P = 0.35), respectively. Visual MD ranged from − 15.58 to − 31.57 dB at presentation and from − 32.96 to − 7.95 dB at final visit. Visual fields MD improved in 5 patients (26.3%), deteriorated in 4 patients (21.1%) and did not significantly change in 10 subjects (52.6%). Possible associations between final visual outcome, measured by BCVA and MD at final visit, and OCT parameters in NAION eyes at each visit were studied using multiple and simple lineal regressions. Mean GCIPL thickness at 3-month follow-up was found to be significantly associated with final BCVA (Final BCVA = − 0.81 + 0.02 × GCIPL at 3-month followup; r2 = 0.32; P = 0.03). Mean RNFL thickness at 6-month follow-up was significantly correlated with final MD (Final MD = − 49.54 + 0.45 × RNFL at 6-month follow-up; r2 = 0.41; P = 0.01).
Discussion Among the numerous reports that have studied NAION subjects, few have analysed retinal tomographic changes in a prospective fashion [2,8—13]. The current study analysed all the available OCT data over a 1-year period of NAION
evolution. It was possible to determine the changes on several variables at the same time, to compare them with a disease-free control group and to study possible correlations with final visual outcomes. The current study showed that, due to the disc edema, the mean retinal nerve fiber layer (RNFL) is thicker (203.63 m at initial visit) in acute NAION than in the control group. It decreased over the following three months with no significant changes from the third month to final visit. These findings are similar to the data published in previous studies [2,4,5,13—15]. Although Contreras et al. showed that the RNFL did not change after 6 months of presentation, most recent papers have reported no changes after three months of follow-up [2,13,14]. Our results confirm these changes using a repeated measures general linear model, which accurately objectivizes the time of RNFL loss stabilization. At presentation, due to optic disc edema in NAION eyes, disc sizes (DS) and neuroretinal rim areas (NRA) were increased, whereas average and vertical cup-disc ratios (C/D) were decreased in comparison with healthy subjects. During the first 3 months of follow-up, the edema disappeared. The changes in cup-disc ratios were progressive whereas disc size and NRA changed abruptly. At 12-month of follow-up, NAION discs tended to have lower cup-disc ratios and higher NRA with no differences in disc size compared to controls. Despite the fact that morphometric and Heidelberg retina tomograph (HRT) studies [16—21] described smaller disc sizes in NAION eyes, our results, in accordance with
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Figure 3. Average macular thickness, mean and sectoral ganglion cell-inner plexiform layer (GCIPL) progression over 1 year of follow-up after non-arteritic ischemic optic neuropathy (NAION). Asterisks show significant differences between groups at each visit. (T-Student and U de Mann—Whitney) A value of P < 0.05 was considered statistically significant.
Contreras et al. and Chan et al., refute this assertion using OCT [22,23]. We suggest that the concept of ‘‘disc at risk’’ in NAION eyes should be identified by the NRA size and C/D ratios rather than by disc size [19,24]. The pattern of disc
changes over the 1-year follow-up observed in our sample was similar to the pattern previously described in other studies. Contreras et al. showed that NRA decreased during the first 6-month of follow-up, and C/D increased after 3-month
Prospective tomographic changes after NAION follow-up [22]. Han et al. reported that both DS and NRA were increased during the first month after presentation, and no significant differences occurred in both parameters at 3-month follow-up [14]. There is considerable controversy about the possible progression of C/D ratios after an episode of NAION. Although some morphometric, HRT and laser polarimetry reports showed lower C/D ratios in NAION eyes compared to their unaffected contralateral eyes, [19,21] Contreras et al. described a rise in C/D ratios using OCT [22]. Our results showed that the C/D changes after NAION were slow, progressive and did not to reach the values of healthy subjects. This study, in agreement with Lee et al., also may suggest that reactive gliosis might play a role in reducing the degree of cupping by compensating for prelaminar tissue loss [25]. This investigation also shows relevant data about ganglion cell-inner plexiform layer thickness (GCIPL) and macular thickness (MT) in NAION eyes. MT thickness progressively decreased during the first 3 months of follow-up and GCIPL thickness decreased during the 6 months after presentation. In contrast to MT, which was elevated at initial visit, GCIPL thickness was always thinner than controls. Similarly, all the sectoral GCIPL thicknesses were thinner than controls over the course of the disease. Interestingly, except for nasal areas, all sectors increased during the first month followed by a drop in their values. During the acute phase, optic disc edema usually impedes correct OCT measurement of the optic disc parameters and may even interfere macular measurements. Therefore, the specific analysis of ganglion cell layer thickness with OCT, rather than disc edema, may be useful to detect the ganglion cell damage. In fact, the pattern of average macular thickness and nasal GCIPL thickness changes may be explained by extension of the optic edema to nasal macular sectors. The increase of the rest of GCIPL thicknesses during the first month of follow-up may be also explained by the presence of cytotoxic edema within the inner layers provoked by ischemia, as has been described in animal models [26,27]. Several studies have reported GCIPL loss before RNFL atrophy. The majority of these papers show that GCIPL gets thinner before 1-2 months after acute NAION [9,10,15,28,29]. In accordance with our findings, a prospective study by De Dompablo et al. reported the GCIPL loss as soon as 2.2 days after the first symptom appeared [8]. This finding also has been supported by other investigations in animal models where apoptosis and ganglion cell degeneration in NAION eyes have been seen two weeks after the ischemic event [30,31]. The current investigation indicates which OCT parameters are related to final visual outcome. Mean GCIPL thickness at 3-month follow-up was found to be significantly associated with final BCVA, and, mean RNFL thickness at 6month follow-up was significantly correlated with final MD. Alasil et al. and Bellusci et al. have reported that RNFL predicts location and severity of final visual field defects [3,32]. In addition, Contreras and colleagues described the correlation between RNFL at 6-month follow-up with visual field and best-corrected visual acuity [2]. Although our findings reveal that GCIPL thicknesses are thinner in NAION eyes at initial visit, it is only at 3-months of follow-up that there is a significant correlation with BCVA. Several investigations have demonstrated the ability of GCIPL to predict visual outcomes
41 in NAION. Although most of the papers described significant correlations after 1 month of presentation, [28,29,33] a recent study by De Dompablo et al. reported this correlation as soon as two weeks after acute NAION [8]. Several limitations of our study should be mentioned. OCT signal strength may affect the quantitative measurements of the parameters studied. In fact, Cheung et al. and Vizzeri et al. demonstrated correlation between signal strength and RNFL thickness [34,35]. Although the uses of corticosteroids and aspirin have not been proved to modify OCT parameters and there is some controversy about their usefulness, we did not classify patients in terms of treatment in the NAION group. Our disease-free control group was composed of healthy subjects who attended our hospital, so the risk of referral bias is not excluded. None ancillary testing has been performed to rule out obstructive sleep apnea syndrome, hence this disease may have been underestimate in the study and control groups. We found that RNFL is thicker in acute NAION compared to controls and decreases during the next 3 months after presentation. In contrast, the GCIPL is thinner in the NAION group compared to controls over the course of the disease. Although, acute NAION eyes have lower CD ratios and higher DS and NRA than controls, there were no significant differences between groups from the third month onwards. The best predictors of final visual function measured by BCVA and MD on VF were GCIPL at 3 months of-follow and RNFL at 6 months of follow-up respectively.
Acknowledgments The authors would like to thank Isabel De Antonio Rubio M.D. for helping with translating into French.
Disclosure of interest The authors declare that they have no competing interest.
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I. García-Basterra et al. [22] Contreras IS, Rebolleda G, Noval S, Oz-Negrete FJM. Optic Disc Evaluation by Optical Coherence Tomography in Nonarteritic Anterior Ischemic Optic Neuropathy. Invest Ophthalmol Vis Sci 2007;48:4084—7. [23] Chan CKM, Cheng ACO, Leung CKS, Cheung CYL, Yung AY, Gong B, et al. Quantitative assessment of optic nerve head morphology and retinal nerve fibre layer in non-arteritic anterior ischaemic optic neuropathy with optical coherence tomography and confocal scanning laser ophthalmoloscopy. Br J Ophthalmol 2009;93:731—5. [24] Hayreh SS, Zimmerman MB. Nonarteritic Anterior Ischemic Optic Neuropathy: Refractive Error and Its Relationship to Cup/Disc Ratio. Ophthalmology 2008;115:2275—81. [25] Lee EJ, Choi YJ, Kim T-W, Hwang J-M. Comparison of the Deep Optic Nerve Head Structure between Normal-Tension Glaucoma and Nonarteritic Anterior Ischemic Optic Neuropathy. PLoS One 2016;11:150242—311. [26] Ho JK, Stanford MP, Shariati MA, Dalal R, Liao YJ. Optical coherence tomography study of experimental anterior ischemic optic neuropathy and histologic confirmation. Invest Ophthalmol Vis Sci 2013;54:5981—8. [27] Maekubo T, Chuman H, Kodama Y, Nao-i N. Evaluation of inner retinal thickness around the optic disc using optical coherence tomography of a rodent model of nonarteritic ischemic optic neuropathy. Jpn J Ophthalmol 2012;57:327—32. [28] Park SW, Ji YS, Heo H. Early macular ganglion cell—inner plexiform layer analysis in non-arteritic anterior ischemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol 2015;254:983—9. [29] Larrea BA, Iztueta MG, Indart LM, Alday NM. Early axonal damage detection by ganglion cell complex analysis with optical coherence tomography in nonarteritic anterior ischaemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol 2014;252:1839—46. [30] Lee GH, Stanford MP, Shariati MA, Ma JH, Liao YJ. Severe, early axonal degeneration following experimental anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci 2014;55:7111—8. [31] Zhang C, Guo Y, Slater BJ, Miller NR, Bernstein SL. Axonal degeneration, regeneration and ganglion cell death in a rodent model of anterior ischemic optic neuropathy (rAION). Exp Eye Res 2010;91:286—92. [32] Alasil T, Tan O, Lu AT-H, Huang D, Sadun AA. Correlation of Fourier domain optical coherence tomography retinal nerve fiber layer maps with visual fields in nonarteritic ischemic optic neuropathy. Ophthalmic Surg Lasers Imaging 2008;39: 71—89. [33] Keller J, Oakley JD, Russakoff DB, Andorrà-Inglés M, Villoslada P, Sánchez-Dalmau BF. Changes in macular layers in the early course of non-arteritic ischaemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol 2016;254:561—7. [34] Cheung CYL, Leung CKS, Lin D, Pang C-P, Lam DSC. Relationship between Retinal Nerve Fiber Layer Measurement and Signal Strength in Optical Coherence Tomography. Ophthalmology 2008;115:1347—51. [35] Vizzeri G, Bowd C, Medeiros FA, Weinreb RN, Zangwill LM. Effect of Signal Strength and Improper Alignment on the Variability of Stratus Optical Coherence Tomography Retinal Nerve Fiber Layer Thickness Measurements. Am J Ophthalmol 2009;148:249—55.
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ORIGINAL ARTICLE
Prospective analysis of macular and optic disc changes after non-arteritic anterior ischemic optic neuropathy Analyse prospective des modifications maculaires et des disques optiques après une neuropathie optique ischémique antérieure non-artéritique I. García-Basterra a,b,∗, A. García-Ben c, F. Ríus-Díaz d, A. González-Gómez a, T.R. Hedges e, L.N. Vuong e, J.M. García-Campos a,f a
Department of Ophthalmology, University Hospital Virgen de la Victoria, Málaga, Spain Department of Ophthalmology, Hospital Costa del Sol, Marbella, Spain c Department of Ophthalmology, University Hospital Santiago de Compostela, Spain d Department of Preventive Medicine, Statistics and Public Health, University of Málaga, Spain e The New England Eye Center, Tufts Medical Center, Tufts University, Boston, USA f Department of Ophthalmology, Centro de Investigaciones Médico-Sanitarias, University of Málaga, Spain b
Received 15 December 2018; accepted 4 March 2019 Available online 6 November 2019
KEYWORDS Ischemic optic neuropathy; Optical coherence tomography
∗
Summary Purpose. — To prospectively analyse macular and optic disc changes after the occurrence of non-arteritic anterior ischemic optic neuropathy (NAION) and study possible predictors of final visual outcome. Methods. — Patients with NAION underwent a complete ophthalmic examination, including spectral-domain optical coherence tomography of the macula and optic nerve head. The examination was repeated 1, 3, 6, 9 and 12 months after onset. Final visual prognosis was evaluated by visual field (VF) and best-corrected visual acuity (BCVA) at the final visit. Data within the NAION group were analysed over the course of the disease and compared to a disease-free control group at each visit. Results. — Twenty-two eyes with NAION and 43 eyes from a control group were included. The retinal nerve fiber layer (RNFL) was significantly thicker in NAION eyes than controls at
Corresponding author at: Department of Ophthalmology, Hospital Virgen de la Victoria, Campus Teatinos, S/N, Málaga, 29010, Spain. E-mail address: [email protected] (I. García-Basterra).
https://doi.org/10.1016/j.jfo.2019.03.034 0181-5512/© 2019 Elsevier Masson SAS. All rights reserved.
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I. García-Basterra et al. presentation (P = 0.00), and significantly decreased during the next 3 months after presentation (P = 0.02). The ganglion cell + inner plexiform layer (GCIPL) was thinner in the NAION group throughout the course of the disease (all P < 0.05). Although the acute NAION eyes had significantly lower cup/disc ratios and higher neuroretinal and disc sizes (all P = 0.00), there were no significant differences between groups from the third month onwards (all P > 0.05). The best predictors of BCVA and VF were GCIPL at 3 months of follow-up (r2 = 0.32; P = 0.03) and RNFL at 6 months of follow-up (r2 = 0.41; P = 0.01) respectively. Conclusions. — RNFL and optic disc changes occur during the first 3 months after the onset of NAION, whereas GCIPL is affected soon after the onset of symptoms. GCIPL and RNFL are useful predictors of final visual outcome. © 2019 Elsevier Masson SAS. All rights reserved.
MOTS CLÉS Neuropathie optique ischémique ; Tomographie par cohérence optique
Résumé Objectif. — Analyser prospectivement les modifications maculaires et papillaires après survenue d’une neuropathie optique ischémique antérieure aiguë (NOIAN) et étudier les facteurs prédictifs du résultat visuel final. Méthodes. — Les patients atteints de NOIAN ont subi un examen ophtalmique complet, comprenant une tomographie par cohérence optique dans le domaine spectral de la macula et de la tête du nerf optique. L’examen est répété 1,3,6,9 et 12 mois après le début. Le pronostic visuel final a été évalué avec le champ visuel (CV) et la meilleure acuité visuelle corrigée (MAVC) lors de la visite finale. Les données du groupe NOIAN ont été analysées au cours de l’évolution de la maladie et comparées à un groupe témoin indemne de la maladie à chaque examen. Résultats. — Vingt-deux yeux atteints de NOIAN et 43 yeux d’un groupe témoin ont été inclus. La couche de fibres nerveuses rétiniennes (CFNR) était significativement plus épaisse dans les yeux NOIAN que chez les témoins lors de la présentation (p = 0,00) et avait diminué de manière significative au cours des trois mois suivant la présentation (p = 0,02). Les cellules ganglionnaires et la couche plexiforme interne (CGCPI) étaient plus minces dans le groupe NOIAN pendant toute la durée de la maladie (p < 0,05). Bien que les yeux avec NOIAN aiguës avaient des ratio C/D significativement plus faibles et des tailles de disque et d’anneau neurorétinien plus élevées (p = 0,00), il n’y a pas eu de différence significative entre les groupes jusqu’au troisième mois (p > 0,05). Les meilleurs prédicteurs de MAVC et CV étaient la CGCPI à 3 mois (r2 = 0,32; p = 0,03) et la CFNR à 6 mois (r2 = 0,41; p = 0,01). Conclusions. — Les modifications de la CFNR et du disque optique se produisent au cours des 3 premiers mois suivant l’apparition de la NOIAN, alors que la CGCPI est affectée peu de temps après l’apparition des symptômes. CGCPI et CFNR sont les meilleurs prédicteurs du résultat visuel final. © 2019 Elsevier Masson SAS. Tous droits r´ eserv´ es.
Introduction Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute optic neuropathy in people over the age of 50. Although its physiopathogenesis is not entirely known, it is assumed to be caused by vascular insufficiency of the optic disc that eventually provokes optic nerve damage [1]. The acute optic nerve injury due to ischemia typically entails significant visual field defects and reduced visual acuity, which tend to be permanent and cause huge impairment in activities of daily living. Optical coherence tomography (OCT) can provide images of the retina and optic nerve that closely resemble histological samples. In NAION, OCT mainly has been used to diagnose and quantify optic disc edema and to monitor peripapillary
retinal nerve fiber layer loss [2—5]. Recent advances in segmentation algorithms have made it possible to visualise and measure individual retinal layers and accurately locate the damage. While most OCT studies of NAION cases have performed retrospective analysis of the optic disc and peripapillary retina both in the acute and chronic stages, few studies have focused on analysing macular and optic nerve changes over the course of the disease. Prospective quantitative and qualitative analysis of optic nerve and macula parameters may help in understanding the pathophysiology of NAION and other optic nerve diseases. The objective of this work is to analyse OCT macular and disc parameters in patients with acute NAION over 1year of follow-up and to compare the measurements with a
Prospective tomographic changes after NAION free-disease group. These variables are also correlated with final visual prognosis, measured as visual acuity and mean deviation on visual field at 12 months of follow-up.
Methods In this prospective observational study, 21 patients with NAION (22 eyes) and a control group composed of 43 patients (43 eyes) were evaluated in University Hospital Virgen de la Victoria from March 2015 to September 2018. The ethics committee of Malaga approved the study according to all federal laws in Spain and the Declaration of Helsinki. Written informed consent was obtained from all subjects. NAION was defined as a sudden and painless visual loss with optic disc swelling and sectoral visual field loss. To rule out anterior ischemic optic neuropathy, all patients were asked for the presence of any symptoms of giant cell arteritis. An examination of the temporal artery and a determination of C reactive protein and erythrocyte sedimentation rate were also performed to completely ruled out this disease. All patients recruited followed a clinical course consistent with ischemic optic neuropathy, with a full resolution of the optic disc edema within 2 months of follow-up. Control subjects were randomly recruited from patients attended for other reasons than retina, vitreous or other optic nerve diseases. Subjects with previous ocular surgery (except cataract surgery), media opacities, coexistence of neurological or systemic diseases or refractive error greater than minus 6 diopters were excluded. All subjects underwent an ophthalmologic examination that included a slit-lamp examination, ophthalmoscopy and tonometry. The best-corrected visual acuity (BCVA) was measured using a Snellen chart at 6 meters. Axial length was measured using IOL Master (Carl Zeiss Meditec, Dublin, CA) and refractometry using an automated refractometer (RM-8900; Topcon, Tokyo, Japan). Automatic visual field (VF) were tested with SITA FAST 30-2 (Swedish Interactive Thresholding Algorithm; Humphrey, Carl Zeiss Meditec, Dublin, CA, USA). Automated VF was performed at the first visit and 12 months after the acute episode on every patient, and the mean deviation (MD) was used for statistical analysis. OCT scanning was performed after pupil dilation with tropicamide 1% (Alcon Cusi, Barcelona, Spain) using Cirrus-OCT (Carl Zeiss Meditec, Dublin, CA, USA) and enhanced-depth imaging technique. Ophthalmic and OCT examinations were repeated 1, 3, 6, 9 and 12 months after the acute episode. Each eye was scanned using an optic disc cube (200 × 200 line scans) protocol and a macular cube (512 × 128 line scans). The scanned areas (6 × 6 mm) were centered on the nerve for retinal nerve fiber layer analysis (RNFL) and on the fovea for ganglion cell-inner plexiform layer (GCIPL) and average macular thickness (MT) analyses. Automatic segmentation algorithms were used to determine the RNFL and GCIPL sectoral thickness (m). The average thickness of the MT, RNFL and GCIPL were automatically obtained by the software and used for analysis. Only scans with uniform brightness and signal strength equal to or greater than 6 in intensity were included in the study. All statistical analyses were performed via Microsoft Excel 2007 (Microsoft Corp., Redmond, WA, USA) and SPSS statistics (IBM-SPSS, Chicago, IL, USA). In the study group,
37 the affected eye was included in the study, whereas for the control group only the right eyes were included. The left eye was only scanned when a low quality image was obtained from the right eye. Sample size was calculated using standard deviation from earlier studies about RNFL thickness [2,3,5—7] (the main variable studied in NAION). OCT measurements of the NAION eyes were evaluated over the course of the disease and compared with the data obtained from the free-disease control group. Chi-Square, T Student and Mann—Whitney U test contrasts for independent samples, considering homoscedasticity, were used to detect differences between groups, linear regression to quantify the relation among parameters and repeated measures general linear model (one-way ANOVA with repeated measures) to analyse changes over the 1 year of follow up. Univariate analyses were also used to look for associations between OCT parameters and final BCVA and MD. R Square, Pearson correlation coefficient, unstandardized coefficient B, test of between-subjects and within-subjects effects with Greenhouse-Geisser and Bonferroni’s post-test corrections, pairwise comparisons and 95% confidence intervals (95% CIs) were presented. All P values were based on 2-sided tests and were considered statistically significant when the values were less than 0.05.
Results Nineteen eyes with NAION and 43 disease-free control eyes were studied. Three patients with NAION were excluded due to coexistence of other neurological or retinal disorders. One patient included his two eyes as acute NAION, one patient had a previous documented episode of NAION in the fellow eye, two patients had optic nerve or visual field findings consistent with previous ischemic damage on their contralateral eyes and 1 patient had only one eye due to an early traumatic injury in the fellow eye. Table 1 provides a distribution of clinical and demographic characteristics of both groups. All individuals included were Caucasians. Except for BCVA (P = 0.00), no statistically significant differences were observed between groups.
Retinal Nerve Fiber Layer Fig. 1 shows the profile plot of average retinal nerve fiber layer (RNFL) thickness one year after initial evaluation. Compared to controls, mean RNFL was significantly thicker in eyes affected with acute NAION (203.63 ± 81.41 m vs. 88.86 ± 10.74 m; P = 0.00) and significantly thinner from the third month of follow-up to the end of the study (59.50 ± 11.52 m vs. 88.86 ± 10.74 m; all P values < 0.05). Repeated measures general linear model showed statistically significant changes of mean RNFL values over time within the group of NAION (Greenhouse-Geisser, F = 16.68; P = 0.02). There was no statistically significant difference in average RNFL between NAION and control group (test of between-subjects P = 0.71). Pairwise comparisons revealed significant differences between initial RNFL and 1 month RNFL and the rest of RNFL values (P values < 0.05). From the 3rd to the 12th month,
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Table 1 Demographic and Clinical Characteristics of Nonarteritic Ischemic Optic Neuropathy Group and Disease-Free Control Group. Variable
NAION (n = 19)
Controls (n = 43)
P value
Age (years) Gender (male/female) BCVA (LogMAR) IOP (mmHg) Axial length (mm) Refractive Error (diopters) Hypertension (Yes/No) Diabetes (type I/type II/No diabetes) Dyslipidemia (Yes/No) Smoking (Yes/No) OSAS (Yes/No)
63.89 ± 12.47 14/5 0.32 ± 0.39 15.33 ± 4.24 22.99 ± 1.18 0.66 ± 2.54 13/6 1/3/15 12/7 4/15 0/19
62.21 ± 11.25 22/21 0.99 ± 0.05 14.29 ± 1.96 23.30 ± 0.82 0.84 ± 1.77 20/23 0/3/40 16/27 7/36 3/40
0.60 0.16 0.00 0.60 0,09 0.77 0.17 0.16 0.10 0.72 0.55
NAION: Nonarteritic Ischemic Optic Neuropathy; BCVA: Best Corrected Visual Acuity; IOP: Intraocular Pressure; OSAS: Obstructive Sleep Apnea Syndrome. Data are presented as mean ± standard deviation. A value of P < 0.05 was considered statistically significant.
neuroretinal rime areas decreased abruptly. At final visit, although average C/D ratios were smaller and NRA bigger in NAION eyes compared to controls, there were no statistically significant differences between groups (P < 0.05). Repeated measures general linear model revealed statistically significant changes of average and vertical CD ratios and DS (Greenhouse—Geisser F = 4.54, F = 5.69, F = 5.48; all P < 0.05), whereas there were no significant changes of NRA over time (P = 0.09). Pairwise comparisons showed that CD changes occurred during three months after presentation; meanwhile changes in DS and NRA were limited to the first month of follow-up.
Ganglion Cell Complex and Average Macular Thickness
Figure 1. Retinal nerve fiber layer progression over 1 year of follow-up after non-arteritic ischemic optic neuropathy (NAION). Asterisks show significant differences between groups at each visit. (T-Student and U de Mann—Whitney) A value of P < 0.05 was considered statistically significant.
there were no statistically significant changes of RNFL values (P values > 0.05).
Optic disc Fig. 2 shows the profile plot of average cup-disc (C/D) ratio, vertical C/D ratio, disc size (DS) and neuroretinal rim area (NRA) over the course of the disease in the NAION group. Compared to controls, both average and vertical C/D ratios were significantly smaller in eyes affected with acute NAION (all P values < 0.05). In contrast, DS and NRA were significantly larger in acute NAION eyes than controls (all P values < 0.05). Over time, C/D ratios progressively increased, whereas disc size and
Fig. 3 shows the profile plots of average macular thicknesses (MT) and mean and sectoral ganglion cell-inner plexiform layer thicknesses (GCIPL) over the 1-year followup. GCIPL thicknesses were significantly thinner in NAION group all over the 1-year of follow-up (all P values < 0.05). Except for nasal GCIPL thicknesses, which progressively decreased over time, all sectoral GCIPL values increased during the first month of follow up and eventually decreased over time. Except for supero-nasal GCIPL thickness, all the thicknesses were significantly different between groups (all P values < 0.05). There were no significant changes of average and sectoral GCIPL thicknesses over time (test of within-subjects: all P values > 0.05). Average macular thicknesses (MT) were significantly thinner in NAION eyes compared to controls at 3, 6, 9 and 12 months of follow-up (all P < 0.05). There were no statistically significant differences between MT at initial and 1-month follow-up between groups (306.57 m and 280.43 m vs. 278.72 m; P > 0.05). The general linear model showed statistically significant changes of average MT over follow-up (P = 0.00). Pairwise comparisons showed that MT changes over time occurred during the first 2 months (P < 0.05).
Prospective tomographic changes after NAION
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Figure 2. Optic disc changes over 1 year of follow-up after non-arteritic ischemic optic neuropathy (NAION). Asterisks show significant differences between groups at each visit. (T-Student and U de Mann—Whitney) A value of P < 0.05 was considered statistically significant.
Visual Prognosis In the NAION group the mean BCVA at first and final visit were 0.32 ± 0.39 and 0.28 ± 0.30 (P = 0.63). BCVA improved in 7 subjects (36.8%), got worse in 6 (31.6%) and 6 did not significantly change at final visit (31.6%). The average MD at first and final visit were − 24.34 ± 5.38 dB and − 23.39 ± 7.10 dB (P = 0.35), respectively. Visual MD ranged from − 15.58 to − 31.57 dB at presentation and from − 32.96 to − 7.95 dB at final visit. Visual fields MD improved in 5 patients (26.3%), deteriorated in 4 patients (21.1%) and did not significantly change in 10 subjects (52.6%). Possible associations between final visual outcome, measured by BCVA and MD at final visit, and OCT parameters in NAION eyes at each visit were studied using multiple and simple lineal regressions. Mean GCIPL thickness at 3-month follow-up was found to be significantly associated with final BCVA (Final BCVA = − 0.81 + 0.02 × GCIPL at 3-month followup; r2 = 0.32; P = 0.03). Mean RNFL thickness at 6-month follow-up was significantly correlated with final MD (Final MD = − 49.54 + 0.45 × RNFL at 6-month follow-up; r2 = 0.41; P = 0.01).
Discussion Among the numerous reports that have studied NAION subjects, few have analysed retinal tomographic changes in a prospective fashion [2,8—13]. The current study analysed all the available OCT data over a 1-year period of NAION
evolution. It was possible to determine the changes on several variables at the same time, to compare them with a disease-free control group and to study possible correlations with final visual outcomes. The current study showed that, due to the disc edema, the mean retinal nerve fiber layer (RNFL) is thicker (203.63 m at initial visit) in acute NAION than in the control group. It decreased over the following three months with no significant changes from the third month to final visit. These findings are similar to the data published in previous studies [2,4,5,13—15]. Although Contreras et al. showed that the RNFL did not change after 6 months of presentation, most recent papers have reported no changes after three months of follow-up [2,13,14]. Our results confirm these changes using a repeated measures general linear model, which accurately objectivizes the time of RNFL loss stabilization. At presentation, due to optic disc edema in NAION eyes, disc sizes (DS) and neuroretinal rim areas (NRA) were increased, whereas average and vertical cup-disc ratios (C/D) were decreased in comparison with healthy subjects. During the first 3 months of follow-up, the edema disappeared. The changes in cup-disc ratios were progressive whereas disc size and NRA changed abruptly. At 12-month of follow-up, NAION discs tended to have lower cup-disc ratios and higher NRA with no differences in disc size compared to controls. Despite the fact that morphometric and Heidelberg retina tomograph (HRT) studies [16—21] described smaller disc sizes in NAION eyes, our results, in accordance with
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Figure 3. Average macular thickness, mean and sectoral ganglion cell-inner plexiform layer (GCIPL) progression over 1 year of follow-up after non-arteritic ischemic optic neuropathy (NAION). Asterisks show significant differences between groups at each visit. (T-Student and U de Mann—Whitney) A value of P < 0.05 was considered statistically significant.
Contreras et al. and Chan et al., refute this assertion using OCT [22,23]. We suggest that the concept of ‘‘disc at risk’’ in NAION eyes should be identified by the NRA size and C/D ratios rather than by disc size [19,24]. The pattern of disc
changes over the 1-year follow-up observed in our sample was similar to the pattern previously described in other studies. Contreras et al. showed that NRA decreased during the first 6-month of follow-up, and C/D increased after 3-month
Prospective tomographic changes after NAION follow-up [22]. Han et al. reported that both DS and NRA were increased during the first month after presentation, and no significant differences occurred in both parameters at 3-month follow-up [14]. There is considerable controversy about the possible progression of C/D ratios after an episode of NAION. Although some morphometric, HRT and laser polarimetry reports showed lower C/D ratios in NAION eyes compared to their unaffected contralateral eyes, [19,21] Contreras et al. described a rise in C/D ratios using OCT [22]. Our results showed that the C/D changes after NAION were slow, progressive and did not to reach the values of healthy subjects. This study, in agreement with Lee et al., also may suggest that reactive gliosis might play a role in reducing the degree of cupping by compensating for prelaminar tissue loss [25]. This investigation also shows relevant data about ganglion cell-inner plexiform layer thickness (GCIPL) and macular thickness (MT) in NAION eyes. MT thickness progressively decreased during the first 3 months of follow-up and GCIPL thickness decreased during the 6 months after presentation. In contrast to MT, which was elevated at initial visit, GCIPL thickness was always thinner than controls. Similarly, all the sectoral GCIPL thicknesses were thinner than controls over the course of the disease. Interestingly, except for nasal areas, all sectors increased during the first month followed by a drop in their values. During the acute phase, optic disc edema usually impedes correct OCT measurement of the optic disc parameters and may even interfere macular measurements. Therefore, the specific analysis of ganglion cell layer thickness with OCT, rather than disc edema, may be useful to detect the ganglion cell damage. In fact, the pattern of average macular thickness and nasal GCIPL thickness changes may be explained by extension of the optic edema to nasal macular sectors. The increase of the rest of GCIPL thicknesses during the first month of follow-up may be also explained by the presence of cytotoxic edema within the inner layers provoked by ischemia, as has been described in animal models [26,27]. Several studies have reported GCIPL loss before RNFL atrophy. The majority of these papers show that GCIPL gets thinner before 1-2 months after acute NAION [9,10,15,28,29]. In accordance with our findings, a prospective study by De Dompablo et al. reported the GCIPL loss as soon as 2.2 days after the first symptom appeared [8]. This finding also has been supported by other investigations in animal models where apoptosis and ganglion cell degeneration in NAION eyes have been seen two weeks after the ischemic event [30,31]. The current investigation indicates which OCT parameters are related to final visual outcome. Mean GCIPL thickness at 3-month follow-up was found to be significantly associated with final BCVA, and, mean RNFL thickness at 6month follow-up was significantly correlated with final MD. Alasil et al. and Bellusci et al. have reported that RNFL predicts location and severity of final visual field defects [3,32]. In addition, Contreras and colleagues described the correlation between RNFL at 6-month follow-up with visual field and best-corrected visual acuity [2]. Although our findings reveal that GCIPL thicknesses are thinner in NAION eyes at initial visit, it is only at 3-months of follow-up that there is a significant correlation with BCVA. Several investigations have demonstrated the ability of GCIPL to predict visual outcomes
41 in NAION. Although most of the papers described significant correlations after 1 month of presentation, [28,29,33] a recent study by De Dompablo et al. reported this correlation as soon as two weeks after acute NAION [8]. Several limitations of our study should be mentioned. OCT signal strength may affect the quantitative measurements of the parameters studied. In fact, Cheung et al. and Vizzeri et al. demonstrated correlation between signal strength and RNFL thickness [34,35]. Although the uses of corticosteroids and aspirin have not been proved to modify OCT parameters and there is some controversy about their usefulness, we did not classify patients in terms of treatment in the NAION group. Our disease-free control group was composed of healthy subjects who attended our hospital, so the risk of referral bias is not excluded. None ancillary testing has been performed to rule out obstructive sleep apnea syndrome, hence this disease may have been underestimate in the study and control groups. We found that RNFL is thicker in acute NAION compared to controls and decreases during the next 3 months after presentation. In contrast, the GCIPL is thinner in the NAION group compared to controls over the course of the disease. Although, acute NAION eyes have lower CD ratios and higher DS and NRA than controls, there were no significant differences between groups from the third month onwards. The best predictors of final visual function measured by BCVA and MD on VF were GCIPL at 3 months of-follow and RNFL at 6 months of follow-up respectively.
Acknowledgments The authors would like to thank Isabel De Antonio Rubio M.D. for helping with translating into French.
Disclosure of interest The authors declare that they have no competing interest.
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