Abstract
Introduction
The treatment of severe optic neuritis (ON) is an emergency, and the role of therapeutic plasma exchange (PLEX) is still debated. The objective of this study was to evaluate the efficacy of the initial combination of parenteral corticosteroid therapy with therapeutic PLEX for the treatment of severe ON. This was a retrospective cohort study conducted between January 1998 and January 2023.
Methods
Therapeutic PLEX was initiated concomitantly with intravenous corticosteroid therapy. The etiological diagnosis of ON was specified as follows: neuromyelitis optica, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and multiple sclerosis. Sixty-five eyes (74.7%) underwent therapeutic PLEX, and 22 eyes (25.3%) received corticosteroid therapy alone.
Results
The mean time to treatment was 7.9 ± 11 days. At 1 year, the mean visual acuity of plasmapheresis patients was 5/10, and that of non-plasmapheresis patients was 1.5/10 (p = 0.008). Five (8.1%) eyes in the PLEX group and 7 (31.8%) eyes in the group treated with corticosteroids alone remained completely blind (p = 0.005). The retinal nerve fiber layer and ganglion cell layer thickness were greater in the PLEX group than in the group treated with corticosteroids alone, 74 ± 23.1 μm versus 59.7 ± 19.3 μm and 24.7 ± 4.3 μm versus 23.3 ± 5.4 μm, respectively. MOGAD and multiple sclerosis patients had the best final visual acuity, 6/10 and 10/10, respectively (p = 0.01). No serious incidents were observed.
Conclusion
This is the largest series of severe ON observed in an Afro-descendant population and treated concomitantly with therapeutic PLEX and systemic corticosteroid therapy at the acute phase. Our study confirms the efficacy of therapeutic PLEX in treating severe ON.
Keywords: Afro-descendant, Multiple sclerosis, Myelin oligodendrocyte glycoprotein antibody-associated disease, Neuromyelitis optica, Optic neuritis, Therapeutic plasma exchange, MS, MOG, MOGAD, NMO, PLEX
Key Summary Points
| Why carry out this study? |
| Severe optic neuritis is most frequently associated with neuromyelitis optica, and its treatment is essentially based on systemic administration of high-dose corticosteroid therapy. However, in many cases, corticosteroid therapy alone is ineffective. The objective of our study is to assess the efficacy of an initial combination of therapeutic plasma exchange with systemic corticosteroid therapy in treating severe optic neuritis. |
| Compared to corticosteroid therapy alone, therapeutic plasma exchange provided better visual acuity recovery (5/10 versus 1.5/10) and reduced the rate of blindness (8.1% versus 31.8%). |
| Therapeutic plasma exchange has been shown to be more effective, both functionally and anatomically, than corticosteroid therapy alone in treating severe optic neuritis. |
| What was learned from the study? |
| These results support the decision to systematically provide corticosteroid-therapeutic plasma exchange combination for the treatment of severe optic neuritis in regions of high prevalence of neuromyelitis optica and in patients at high risk of neuromyelitis optica, without waiting for the failure or lack of efficacy of corticosteroid therapy alone. |
Introduction
Optic neuritis (ON) is one of the leading causes of acute or subacute decrease in visual acuity in patients under 50 years of age. It is mostly related to central nervous system demyelinating inflammatory diseases, such as neuromyelitis optica (NMO), which bears the worst prognosis [1, 2]. NMO is an astrocytopathy characterized by the presence of autoantibodies directed against aquaporin 4 (anti-AQP4) in approximately 80% of patients. Among seronegative patients, 30% carry antibodies directed against myelin oligodendrocyte glycoprotein (anti-MOG) [3]. NMO is a rare yet widespread disease, whose distribution across the world varies according to ethnic origin. The Caribbean, and especially the island of Martinique, has one of the highest incidence and prevalence rates in the world, 7.3 per million person-years and 10 per million person-years, respectively [4]. Martinique is a French territory located in the Lesser Antilles, French West Indies (FWI). This Caribbean island has about 361,000 inhabitants, who are mainly Afro-Caribbean. Due to its historical past, most of the population is of African descent (AD), with ethnic and genetic roots in Central and West Africa [5]. The population structure consists mainly of Afro-Caribbeans (> 90%), with some interbreeding with the Caucasian population (estimated at < 20%).
Severe ON is most frequently associated with NMO, and its treatment is essentially based on systemic administration of high-dose corticosteroid therapy. However, in many cases, corticosteroid therapy alone is ineffective, and unless the etiological diagnosis was made during a previous flare-up, the presence of specific autoantibodies to enable an etiological diagnosis is not readily apparent [6]. The Optic Neuritis Treatment Trial (ONTT) showed that the prognosis of severe ON, characterized by a significant decrease in visual acuity, correlated with poor visual recovery after systemic corticosteroid therapy [7]. Regularly confronted with the severity of functional sequelae, since 2007 we have combined plasma exchange (PLEX) sessions with corticosteroid therapy straightaway, without waiting for serological results—firstly, for spinal cord relapses, then for severe ON [8, 9]. Indeed, by removing autoantibodies, therapeutic PLEX has been proven effective in several neurological conditions that share the same pathophysiological mechanisms [10]. Encouraging results, mostly obtained retrospectively, have thus regularly been reported, and have confirmed the superiority of therapeutic PLEX combined with corticosteroid therapy, even though in most studies, therapeutic PLEX was initiated after the failure of corticosteroid therapy [8, 9, 11–15].
The main objective of our retrospective, single-center study was to assess the efficacy of the initial combination of therapeutic PLEX with systemic corticosteroid therapy in treating severe ON, especially that related to NMO.
Methods
Study Design and Participants
This was a retrospective cohort study conducted at the University Hospital of Martinique, the only hospital on the island to provide ophthalmic emergency care. We selected observations of first severe ON flare-up treated between January 1998 and January 2023, with at least 1 year of follow-up. Severe ON was defined by visual acuity less than or equal to 20/200 in one eye, or a synchronous binocular affection. An ocular or medullary flare-up was defined as the onset or worsening of signs or symptoms for at least 24 h. None of the patients had a history of familial, infectious, vascular, compressive, systemic, toxic, or deficiency-related optic neuropathies. They were all HIV (human immunodeficiency virus)- and HTLV-1 (human T-lymphotropic virus type 1)-seronegative. We excluded patients with less than 1 year of follow-up and those with eye diseases or taking treatment likely to reduce visual acuity. The diagnosis of acute myelitis was made when there were medullary manifestations comprising sphincter, sensory, or motor disorders, with the maximum deficit occurring in less than 4 weeks. All patients were examined by neurologists specializing in central nervous system demyelinating diseases, and etiological diagnosis was made in accordance with the latest international diagnostic reference [16]. NMO diagnosis was based on diagnostic criteria proposed in 1999 by Wingerchuk, revised in 2006 and then 2015 [17–19]. The diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) was made in reference to diagnostic criteria established in 2023 [20]. The search for anti-AQP4 and anti-MOG autoantibodies was carried out on living cells (cell-based assay, CBA) transfected with AQP4 and MOG (INSERM U842, Lyon, France). The detection of MOG antibody was based on living MOG-transfected human embryonic kidney (HEK) cells [21].
Consent was provided by each participant. The study protocol was reviewed and approved by the Institutional Review Board (IRB) of the University Hospital of Martinique (CPP: Comité de Protection des Personnes) IRB number 2024/043. The primary mission of the CPP is to ensure the ethical implementation of research. They carry out their mission with constant concern for the protection of individuals from both a legal and ethical perspective. The study procedures were fulfilled in agreement with the Declaration of Helsinki.
Ophthalmic Examination
Each patient underwent a complete ophthalmological examination, including a precise refractive test and visual acuity as measured by the Snellen chart. Visual acuity values were converted into logMAR (logarithm of the minimum angle of resolution) to compute the means. LogMAR values were categorized as follows: 1.7 for counting fingers, 2.0 for hand motion, 2.3 for light perception, and 3.0 for no light perception. The visual acuity gain was calculated as the difference between the visual acuity reported at the acute phase of ON and visual acuity at 1 year. Perimetry testing was performed using the Humphrey visual field (Humphrey Field Analyzer 750 II, Carl Zeiss). We employed a 24-2 threshold test (54 points tested) with the FASTPAC strategy to obtain the foveal threshold (FT), the corrected total mean deviation (MD), and the standard deviation of differences between the threshold value and the expected value (pattern standard deviation [PSD]). The visual field abnormalities were ranked in 21 categories based on the ONTT classification, reorganized into three principal groups: localized, diffuse, and artifactual [22]. When static visual field testing was not possible, a Goldmann kinetic visual field test was carried out. Peripapillary retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thicknesses were measured using spectral domain optical coherence tomography (SD-OCT) (Spectralis® OCT, Heidelberg Engineering, Germany). OCT image segmentation was verified, and the quality of the selected scans was ≥ 7. In the case of a narrow pupil, OCT was performed after the instillation of a drop of tropicamide.
Plasmapheresis
High-dose corticosteroid therapy (methylprednisolone, 1 g/day) was administered for 3 to 10 days. Five consecutive plasma exchanges were performed daily in a medical intensive care unit, which could be repeated in the case of insufficient response. During each cycle, a certain volume of plasma was exchanged with 5% albumin solution. After five exchanges, more than 90% of immunoglobulin was eliminated. An anticoagulant treatment was systematically added. In addition to clinical monitoring, the main biological tests included inflammation parameters, complete blood count, platelets, albumin, electrolytes, and fibrinogen. We noted the occurrence of possible side effects. The time between clinical symptom onset and the start of the treatment was reported. Observations from severe ON cases that had not been treated with PLEX but with high-dose corticosteroid therapy only allowed us to build a comparative group. This latter group largely comprised the earliest patients (between 1998 and 2005) or those who had refused PLEX or who could not undergo plasmapheresis because they could not be taken in the medical intensive care unit.
Statistical Analysis
Comprehensive computerized data analysis was performed anonymously. Continuous data were calculated and presented as mean ± standard deviation (SD) or median with interquartile range. Categorical data were reported as proportions and percentages. When variable distribution was non-normal and non-parametric, we used the Wilcoxon test to compare two groups, and the Kruskal–Wallis test was used for multiple comparisons. For variables with a normal distribution, the Student t-test allowed us to compare two groups, and we used the analysis of variance (ANOVA) test when we had to model several variables. We considered criteria such as age, gender, time to treatment, and background treatment as confounding factors. Statistical analyses were carried out using SAS software (SAS Institute Inc., Carry, NC, USA), version 9.4.
Results
Demographic Characteristics
Sixty-four patients were included. Four patients were treated with corticosteroids alone for one eye and with PLEX for the second eye (Table 1). All patients were of African descent. Fifty-four (84.4%) were female and 10 (15.6%) were male. The mean age was 39.9 ± 15.1 years. Thirty-six patients (56.3%) had a history of unilateral ON, and 28 (43.8%) bilateral ON. Five patients were affected bilaterally, but only one eye was included because the ON of the contralateral eye was not recent and was not severe. The number of AQP4+ NMO patients was 26 (40.6%), with 15 (23.5%) AQP4− NMO patients. There were 10 patients (15.6%) with MOGAD, eight (12.5%) with multiple sclerosis (MS), and five (7.8%) with idiopathic ON (ION). Forty-eight patients were treated with PLEX, and 12 with corticosteroid therapy alone. There was no significant difference in age, gender, unilateral or bilateral involvement, or etiological diagnosis between patients treated with or without PLEX. The number of cases with a history of severe bilateral ON was greater in the PLEX group. The mean follow-up duration was 2.7 ± 2.4 years.
Table 1.
Demographic characteristics
| PLEX | Corticosteroid therapy | Total | p-value | |
|---|---|---|---|---|
| Number of cases | 48 | 12 | 64 | – |
| Age (years) | 39.8 ± 15 | 42.3 ± 15.4 | 39.9 ± 15.1 | 0.6 |
| Gender ratio [F/M (% F)] | 40 (83.3%) | 10 (83.3%) | 54 (84.4%) | 1 |
| Bilateral affection | 23 (47.9%) | 1 (8.3%) | 28 (43.8%) | 0.01 |
| AQP4+ NMO | 19 (39.6%) | 6 (50%) | 26 (40.6) | 0.69 |
| AQP4− NMO | 13 (27.1%) | 1 (8.3%) | 15 (23.4) | |
| MOGAD | 7 (14.6%) | 2 (16.7%) | 10 (15.6) | |
| MS | 6 (12.5%) | 2 (16.7%) | 8 (12.5) | |
| ION | 3 (6.3%) | 1 (8.3%) | 5 (7.8) |
PLEX plasma exchange, F female, M male, AQP4 aquaporin 4, NMO neuromyelitis optica, MOGAD myelin oligodendrocyte glycoprotein antibody-associated disease, MS multiple sclerosis, ION idiopathic optic neuritis
Eighty-seven cases of severe ON were selected. Clinical and etiological characteristics are depicted in Table 2. Approximately 60% of patients with NMO had an ON as first disease manifestation. An optic disc swelling was present in 84.6% patients with MOGAD. The mean time to treatment, i.e., the mean time between symptom onset and treatment initiation, was 7.9 ± 11 days. Sixty-five (74.7%) eyes underwent therapeutic PLEX, and 22 (25.3%) received corticosteroid therapy alone.
Table 2.
Etiology characteristics and treatment performed
| AQP4+ NMO | AQP4− NMO | MOGAD | MS | ION | Total | |
|---|---|---|---|---|---|---|
| Number of cases | 36 (41%) | 21 (24%) | 13 (15%) | 8 (10%) | 9 (10%) | 87 (100%) |
| Inaugural ON | 22 (61.1%) | 12 (57.1%) | 11 (84.6%) | 4 (50%) | 8 (88.9%) | 57 (65.5%) |
| Papilledema | 9 (26.5%) | 11 (52.4%) | 11 (84.6%) | 3 (37.5%) | 6 (66.7%) | 40 (47.1%) |
| Time to treatment (days) | 11.1 ± 1.6 | 5.5 ± 4.4 | 3.8 ± 2.7 | 2.7 ± 1.4 | 10 ± 5.5 | 7.9 ± 11 |
| Corticosteroid therapy | 9 (40.9%) | 3 (13.6%) | 4 (18.2%) | 2 (9.1%) | 4 (18.2%) | 22 (25.3%) |
| PLEX | 27 (75%) | 18 (85.7%) | 9 (69.2%) | 6 (75%) | 5 (55.6%) | 65 (74.7%) |
| PLEX 2–7 days | 7 (25.9%) | 7 (38.9%) | 5 (55.6%) | 1 (16.7%) | 1 (20%) | 21 (32.3%) |
| PLEX > 7 days | 20 (74.1%) | 11 (61.1%) | 4 (44.4%) | 5 (83.3%) | 4 (60%) | 44 (66.2%) |
AQP4 aquaporin 4, NMO neuromyelitis optica, MOGAD myelin oligodendrocyte glycoprotein antibody-associated disease, MS multiple sclerosis, ION idiopathic optic neuritis, ON optic neuritis, Time to treatment time to ON treatment, Corticosteroid therapy corticosteroid therapy alone, PLEX plasma exchange, PLEX 2–7 days duration of plasmapheresis between 2 and 7 days, PLEX > 7 days duration of plasmapheresis greater than 7 days
Visual Function
The initial mean visual acuity was reduced to counting fingers at 50 cm in all patients. ON cases treated with PLEX fared better at 1 year than those treated with corticosteroid therapy alone. At 1 year, the mean visual acuity in the plasmapheresis group was 5/10, whereas that of the non-plasmapheresis group was 1.5/10. The difference between the two groups was significant (p = 0.008) (Table 3). When adjusted for visual acuity and etiological diagnosis (ANOVA), the gain in visual acuity was greater in patients managed with PLEX than with corticosteroids alone. Improvement in FT, MD, and PSD was most notable in PLEX-treated patients, but the difference was not significant. At 1 year, 26 (41.9%) eyes in the PLEX group and seven (31.8%) eyes in the corticosteroids alone group had a normal visual field; however, the difference was not significant (p = 0.49). At 1 year, five (8.1%) eyes treated with PLEX and seven (31.8%) eyes treated with corticosteroid therapy alone remained completely blind, and the difference was significant (p = 0.005). At 1 year, RNFL and GCL were thicker in the PLEX group than in the group treated with corticosteroids alone (74 ± 23.1 μm versus 59.7 ± 19.3 μm and 24.7 ± 4.3 μm versus 23.3 ± 5.4 μm, respectively), but the difference was not significant. AQP4+ and AQP4− NMO patients managed with plasmapheresis had initial visual acuity of 5/10 (1.51 ± 0.88 logMAR) and counting fingers (1.95 ± 0.58 logMAR), respectively (Table 4).
Table 3.
Outcomes of PLEX versus corticosteroid therapy alone
| PLEX | Corticosteroid therapy alone | p-value | |
|---|---|---|---|
| Number of cases | 65 | 22 | – |
| Initial VA | 1.7 ± 0.79 | 1.69 ± 0.73 | 1 |
| LP− cases (%) | 5 (8.1%) | 7 (31.8%) | 0.005 |
| VA at 1 year | 0.32 ± 0.68 | 0.92 ± 1.01 | 0.008 |
| VA gain | −1.38 ± 0.88 | −0.77 ± 1.03 | 0.0006 |
| Initial FT | 16.9 ± 14.9 | 10 ± 13.5 | 0.52 (Wilcoxon) |
| FT at 1 year | 29.1 ± 10.8 | 20.5 ± 16.4 | |
| FT gain | 12.4 ± 14.2 | 6.5 ± 20.4 | |
| Initial MD | −14.59 ± 10.21 | −17.14 ± 12.27 | 0.24 (Student) |
| MD at 1 year | −5.68 ± 6.31 | −12.95 ± 11.63 | |
| MD gain | 9.36 ± 10.42 | 2.14 ± 16.37 | |
| Initial PSD | 6.87 ± 3.84 | 5.29 ± 3.87 | 0.49 (Student) |
| PSD at 1 year | 3.98 ± 2.85 | 5.1 ± 3.81 | |
| PSD gain | −2.46 ± 4.39 | −0.81 ± 5.08 | |
| Initial RNFL (μm) | 136.1 ± 60.1 | 142.3 ± 94.8 | 0.5 (Wilcoxon) |
| RNFL at 1 year (μm) | 74 ± 23.1 | 59.7 ± 19.3 | |
| RNFL loss (μm) | 60 ± 64.7 | 82.2 ± 88.6 | |
| Initial GCL (μm) | 30.3 ± 5.2 | 29.6 ± 4.4 | 0.41 (Student) |
| GCL at 1 year (μm) | 24.7 ± 4.3 | 23.3 ± 5.4 | |
| GCL loss (μm) | 4.6 ± 5.5 | 6.4 ± 4.7 |
VA visual acuity, LP light perception, FT foveal threshold, PLEX plasma exchange, MD mean deviation, PSD pattern standard deviation, RNFL retinal nerve fiber layer thickness, GCL ganglion cell layer thickness
Table 4.
Outcomes of PLEX according to etiological diagnosis
| AQP4+ NMO | AQP4− NMO | MOGAD | MS | ION | Total | |
|---|---|---|---|---|---|---|
| Number of cases | 27 | 18 | 9 | 6 | 5 | 65 |
| Initial VA | 1.51 ± 0.88 | 1.95 ± 0.58 | 1.87 ± 0.88 | 1.65 ± 0.62 | 1.58 ± 0.89 |
0.24 (ANOVA) |
| VA at 1 year | 0.41 ± 0.74 | 0.3 ± 0.7 | 0.28 ± 0.83 | 0.03 ± 0.05 | 0.32 ± 0.29 | |
| VA gain | −1.1 ± 0.91 | −1.65 ± 0.77 | −1.59 ± 1.01 | −1.62 ± 0.59 | −1.26 ± 0.95 | |
| Initial RNFL (μm) | 108 ± 45 | 141 ± 55 | 179 ± 65 | 147 ± 70 | 182 ± 73 |
0.04 (Kruskal–Wallis) |
| RNFL at 1 year (μm) | 69 ± 25 | 70 ± 17 | 80 ± 27 | 88 ± 9 | 80 ± 25 | |
| RNFL loss (μm) | 36 ± 52 | 67 ± 58 | 103 ± 86 | 58 ± 76 | 91 ± 66 | |
| Initial GCL (μm) | 29.6 ± 4.1 | 30.3 ± 5.9 | 32 ± 8.1 | 29 ± 0.8 | 30.3 ± 2.2 |
0.81 (ANOVA) |
| GCL at 1 year (μm) | 23.3 ± 4.9 | 25.1 ± 3.5 | 26.4 ± 5 | 25.2 ± 2.9 | 25.4 ± 4.1 | |
| GCL loss (μm) | −3.5 ± 3.3 | −5.3 ± 7 | −6.5 ± 7.8 | −3.3 ± 3.8 | −3.3 ± 2.5 |
AQP4 aquaporin 4, NMO neuromyelitis optica, MOGAD myelin oligodendrocyte glycoprotein antibody-associated disease, MS multiple sclerosis, ION idiopathic optic neuritis, VA visual acuity (logMAR), RNFL retinal nerve fiber layer thickness, GCL ganglion cell layer thickness, ION idiopathic optic neuritis
At 1 year, mean visual acuity was 4/10 (0.41 ± 0.74 logMAR) in AQP4+ patients, and 5/10 (0.30 ± 0.70 logMAR) in AQP4− patients. Patients with MOGAD had a mean visual acuity of 0.02 (1.87 ± 0.88 logMAR) initially, and 6/10 (0.28 ± 0.83 logMAR) at 1 year (Table 4). Using the ANOVA model, patients with MOGAD and MS had the best final visual acuity, 6/10 and 10/10, respectively (p = 0.01). Before PLEX treatment, 15 eyes (23%) had complete vision loss (II4a according to ONTT classification) compared to only five eyes (7.7%) at 1 year (p < 0.01). Apart from usual side effects of high-dose intravenous corticosteroid therapy (namely, euphoria, irritability, insomnia, etc.), we did not witness any serious incidents. In addition to small hematoma at the puncture site in patients treated with PLEX, we also noted bacteremia without sepsis, vasovagal syncope, transient arterial hypotension, and hypofibrinogenemia.
Discussion
We report the outcomes of the largest series of severe ON in an Afro-descendant population treated concomitantly with PLEX and systemic corticosteroid therapy at the acute phase. In fact, in most studies, PLEX is not initiated until systemic corticosteroid therapy fails, as often evidenced by more than 2 weeks of delay in PLEX implementation. Time to PLEX initiation was 34 days in the French single-center study by Deschamps et al. and 2.6 weeks in the Chinese multicenter study by Chen et al. [12, 13, 23]. Several studies have demonstrated, for ON related to both NMO and MOGAD, that a delay in the start of treatment was correlated to poor functional and anatomical recovery [24].
Our choice to systematically combine PLEX with corticosteroid therapy was mainly dictated by the fact that our department is in an area with a high prevalence of NMO. Moreover, when patients present with a first ON episode, their serology status is not known. Despite poor documentation on the subject, we also know that the prognosis for ON in AD patients is worse than in White patients [25]. AD patients are usually underrepresented in the different series. In the study by Chen et al., among 317 patients, there were 69% White, 14% Black, 6.5% Asian, and 6% Hispanic patients [23]. In a UK cohort of NMO cases, Afro-Caribbean patients had earlier disease onset, a higher count of cerebral and ocular flare-ups, and a greater risk of visual impairment than Caucasian subjects [26]. In a study conducted in Colorado, USA, and including 115 seropositive NMO cases, the most serious attacks were observed in AD patients [27].
Therapeutic PLEX was shown effective from both a functional and anatomical perspective. Compared with corticosteroid therapy alone, it resulted in better visual acuity recovery (5/10 versus 1.5/10), reduced blindness (8.1% versus 31.8%), limited reduction in the thickness of the peripapillary retinal nerve fiber layer (74 ± 23.1 μm versus 59.7 ± 19.3 μm), and ganglion cell layer thickness (24.7 ± 4.3 μm versus 23.3 ± 5.4 μm). The greatest visual acuity gains were obtained in the MOGAD and MS groups. Our results are consistent with those of most studies, confirming the efficacy of therapeutic PLEX. The Chinese series by Fu et al. gathered 117 acute ON cases, encompassing 93 AQP4, six MOG, and 10 ION. In the AQP4 group, the initial mean visual acuity, visual acuity after the failure of corticosteroid therapy, and visual acuity 6 months after PLEX were 3.33 ± 1.51, 2.22 ± 1.21, and 1.85 ± 1.52, respectively. According to these authors, therapeutic PLEX contributed to improved visual acuity. It was even more effective when initiated early. Beyond 60 days, an improvement was unlikely [12]. As demonstrated by the ONTT, poor visual acuity at 1 month predicts poor visual acuity at 6 months [7]. The results obtained by Chen et al. are better than ours: the final visual acuity was 0.1 logMAR or approximately 8/10. This series included more patients with MS (27.3%) and MOG (23.3%) than ours, which included 10% patients with MS and 15% with MOG. The prognosis for ON related to MS or MOG is usually better than for NMO [23]. As in our series, the best results were reported in patients with MOG whose final visual acuity was 0 logMAR or 20/20. For Chen et al., there was a correlation between the time to PLEX implementation and the results obtained. The probability of complete visual acuity recovery decreased with the delay in PLEX implementation [23]. More than half of the patients in the series of Deschamps et al., which included 14 MS, 15 NMO, and 12 ION, achieved final visual acuity of more than 5/10. As in the study by Chen et al., patients with a history of ON in the same eye did not recover after PLEX [13, 23]. For Abboud et al., a background treatment at the time of the flare-up with an immunosuppressant such as rituximab, mycophenolate mofetil, azathioprine, or prednisone helped to improve the prognosis of a flare-up treated with PLEX [14]. In the series by Ruprecht et al., the worst outcomes were observed in patients treated the latest [28].
The study by Song et al. included 15 patients (23 eyes) with NMO and treated with PLEX. All patients were of Chinese origin. The time between corticosteroid therapy and PLEX implementation was 1.6 days. Therapeutic PLEX was more effective than corticosteroid therapy alone. Functional improvement was achieved in patients with initial absence of light perception. This study highlighted the decreasing efficacy of corticosteroid therapy alone with the number of flare-ups, as opposed to therapeutic PLEX, which still allowed visual improvement in these patients [29].
Therapeutic PLEX has also been proven effective in demyelinating inflammatory diseases of the central nervous system in children. The study by Savransky et al. included 35 ON cases treated with PLEX after failure of intravenous corticosteroid therapy. A significant increase in visual acuity was quickly obtained, as well as at 3 and 6 months. The proportion of side effects was 5.9% for PLEX in this study. As for most studies, it had no control group and was retrospective [30]. Side effects related to PLEX are infrequent in our series, as in most studies. Nonetheless, PLEX requires prolonged monitoring, an adapted infrastructure, and a staff trained in this technique. Yoshida et al. reported anaphylactic shock in a patient with NMO treated with PLEX for bilateral ON [31].
For severe spinal cord flare-ups, systemic corticosteroid therapy only allows partial functional recovery, and the best results are achieved with PLEX [8]. Similarly, our study confirms that better results are obtained when PLEX is immediately combined with corticosteroid therapy. PLEX is effective in all severe ON etiologies (AQP4+, AQP4−, MS, MOG, ION, etc.). Anti-NMO antibody positivity is not essential for the effectiveness of PLEX [32]. By eliminating agents responsible for inflammation, such as autoantibodies, complement fractions, and cytokines, PLEX is even more effective when started early. Associated with corticosteroid therapy, it may help limit demyelination and axonal damage. Usually used as background treatment, eculizumab, a monoclonal antibody directed against complement C5 fraction, has recently shown effectiveness in the management of acute ON that did not respond to corticosteroid therapy and PLEX [33, 34].
The limitations of our study are primarily related to the methodology. This is a single-center, retrospective study. There was no sample size calculation and no randomization for the choice of treatment. A prospective study would allow for the best assessment of the efficacy of PLEX. However, it would be difficult to implement given the proven benefit of plasmapheresis, both visually and generally, in patients with sometimes life-threatening prognosis.
Conclusion
Our study confirms the efficacy of therapeutic PLEX in the treatment of severe ON, as well as the merits of combining it, from the beginning, with corticosteroid therapy. Knowing the risk of permanent vision loss associated with severe ON, it is a matter of urgency to promptly initiate the treatment. These results support our decision to systematically provide corticosteroid–PLEX combination for the treatment of severe ON in regions of high prevalence of NMO and in patients at high risk of NMO, without waiting for the failure or lack of efficacy of corticosteroid therapy alone.
Acknowledgements
We would like to thank the participants of this study.
Author Contributions
Marie Jugnet: design, statistical analysis, drafting the manuscript. Thomas David: data collection. Mitta Pierre: drafting the manuscript. Ruddy Valentino: data collection. Hossein Mehdaoui: data collection. Harold Merle: concept, design, data collection, drafting the manuscript.
Funding
No funding or sponsorship was received for this study or publication of this article. The rapid service fee was funded by the authors: Delegation for Clinical Research and Innovation (DRCI), University Hospital of Martinique, French West Indies, France.
Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Conflict of Interest
The authors Marie Jugnet, Thomas David, Mitta Pierre, Ruddy Valentino, Hossein Mehdaoui, and Harold Merle have nothing to disclose.
Ethical approval
The authors received consent from each participant. The study protocol was reviewed and approved by the Institutional Review Board of the University Hospital of Martinique (CPP: Comité de Protection des Personnes), IRB number 2024/043. The primary mission of the CPP is to ensure the ethical implementation of research. They carry out their mission with a constant concern for the protection of individuals from both a legal and ethical perspective. The study procedures were fulfilled in agreement with the Declaration of Helsinki.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.