Fundus Changes in the Offspring of Mothers With Confirmed Zika Virus Infection During Pregnancy in French Guiana, Guadeloupe, and Martinique, French West Indies.

Importance: Most ocular lesions have been described for children with congenital Zika syndrome. The frequency of finding ocular abnormalities is unknown among children exposed to Zika virus (ZIKV) during pregnancy. This study was conducted on newborns whose mothers were positive for ZIKV, confirmed with reverse-transcription polymerase chain reaction (RT-PCR) testing. Objective: To report ocular fundus manifestations in newborns with congenital ZIKV exposure in French Guiana, Martinique, and Guadeloupe, French West Indies, to assess its prevalence. Risk factors, such as the presence of extraocular fetopathies and the gestational term at infection, were sought. Design, Setting, and Participants: This was a cross-sectional multicentric study, conducted from August 1, 2016, to April 30, 2019, for which data were collected prospectively. The study inception was at the beginning of 2016 from the onset of the ZIKV epidemic in the French West Indies. Newborns whose mothers tested positive (by RT-PCR) for ZIKV during pregnancy were included. Interventions: Fundus examination was performed using widefield retinal imaging after pupil dilation. Infection date, delivery mode, and newborn measurements were collected. Main Outcomes and Measures: Anomalies of the vitreous, choroid, retina, and optic disc. Results: A total of 330 children (mean [SD] age, 68 [IQR, 22-440] days; 170 girls [51.5%]) were included. Eleven children (3.3%) had perivascular retinal hemorrhages, and 3 (0.9%) had lesions compatible with congenital ZIKV infection: 1 child had torpedo maculopathy, 1 child had a chorioretinal scar with iris and lens coloboma, and 1 child had a chorioretinal scar. Retinal hemorrhages were found at childbirth during early screening. Lesions compatible with congenital ZIKV infection were not associated with the presence of extraocular fetopathy. Microcephaly was not associated with lesions compatible with congenital ZIKV infection (odds ratio [OR], 9.1; 95% CI, 0.8-105.3; P = .08), but severe microcephaly was associated with an OR of 81 (95% CI, 5.1-1297.8; P = .002). Conclusions and Relevance: Results of this cross-sectional study suggest that the ocular anomalies found may be associated with ZIKV in 0.9% of the exposed population. Ocular lesions were rare, affected mostly the choroid and retina, and seemed to be associated with choroiditis-related scarring that developed during fetal growth.

Class II Human Leukocyte Antigen (HLA) and Susceptibility to Polypoidal Choroidal Vasculopathy in Afro-Caribbean Descent.

Purpose: To evaluate how the HLA genotype is associated to the polypoidal choroidal vasculopathy (PCV) in a population of patients of Afro-Caribbean descent. Methods: Forty-seven patients were diagnosed with PCV. The number of control patients was 457. All affected patients and control patients were of Afro-Caribbean descent and natives to Martinique. HLA typing was based on blood sample, using the polymerase chain reaction technique. Comparison of HLA alleles between the 2 groups was done using chi-2 test, odds ratio (OR) and confidence interval using Woolf's method. The Bonferroni correction was considered significant when p-value ≤0.05. Alleles frequency was analyzed for DRB1 and DQB1 locus. Results: HLA-DRB1*13 allele was significantly associated to PCV (OR = 2.02, CI = [1.3; 3.13], p = 0.003). In group DRB1, the Bonferroni correction significance threshold was <0.004. HLA-DQB1*04 allele was significantly associated to PCV (OR = 3.5, CI = [1.48; 8.3], p = 0.006). In group DQB1, the Bonferroni correction significance threshold was <0.006. Conclusion: Two HLA alleles are positively associated to PCV. The possible association between PCV and certain alleles suggest HLA implication in PCV pathogeny, most likely by modeling the immune system response.

Bruch Membrane Opening Minimum Rim Width in Neuromyelitis Optica.

BACKGROUND: Optical coherence tomography (OCT) analyzes the neurodegeneration in neuromyelitis optica (NMO) and multiple sclerosis (MS) and quantifies optical atrophy. The retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness are decreased, and this structural change is correlated with visual function of patients, including contrast vision and visual field deviation. The main objective of this study was to evaluate the Bruch membrane opening minimum rim width (BMO) of the patients with NMO. METHODS: We studied the thickness of the BMO by OCT, in patients with NMO (n = 25; 34 eyes), MS (n = 50; 70 eyes), and a control group (n = 51; 100 eyes). The study evaluated the structure-function relationship with the correlation between OCT and visual function: Visual acuity, Pelli-Robson score, Sloan 2.5 and 1.25, color vision, standard automated perimetry (SAP), and frequency-doubling technology perimetry (FDT). RESULTS: The average thickness of BMO was significantly reduced in NMO and MS with or without a history of optic neuritis (ON). Significant thinning of the average, nasal, and inferonasal BMO in the absence of ON in NMO was found compared with controls (P = 0.022, 0.006, and 0.026, respectively). BMO was strongly correlated with Pelli-Robson score (P < 0.001), Sloan 2.5 (P < 0.001), and mean deviation of SAP and FDT (P = 0.004). The sectorial study found a high correlation between the BMO and the corresponding sector of the visual field. CONCLUSIONS: The BMO thickness is decreased after ON in NMO and MS. This study showed an improved ability of BMO over RNFL and GCL to detect infraclinical impairment in patients with NMO without a history of optic neuropathy. Like the RNFL and GCL, BMO is well correlated with visual function, including contrast vision and visual field deviation.

Case Report: Two Cases of Keratoconjunctivitis Tied to Sargassum Algae Emanations.

Since 2011, considerable amounts of Sargassum algae regularly end up on beaches in the Gulf of Mexico, the Caribbean, and in the French overseas departments. We report observations of two bilateral keratoconjunctivitis associated with important functional symptomatology. There was a conjunctival hyperemia and superficial punctate keratitis. The ocular impairment would repeat at every algae ashore landing. Clinical examination, history, and time line of symptomatology onset allowed us to eliminate the classic etiologies of bilateral keratoconjunctivitis and to suggest an irritant toxic origin tied to hydrogen sulfide. This is the first description of ocular impairment tied to Sargassum algae decomposition. Their decomposition, through H2S emission, can be at the origin of bilateral keratoconjunctivitis. Ocular impairment is often at the forefront of complaints made by individuals exposed to H2S.

Ocular manifestations in Congenital Zika syndrome: About a case of torpedo maculopathy.

PURPOSE: To describe pertinent imaging studies and clinical features of a torpedo maculopathy presumably associated with congenital Zika syndrome. OBSERVATION: A 23-month-old child, with no prematurity or microcephaly at birth, was examined in the Ophthalmology department of the University Hospital of Fort-de-France (Martinique, French West Indies), as part of a systematic screening of malformations in children suspected of maternal-fetal exposure to Zika virus. Zika infection was confirmed in the mother's serum by Reverse Transcriptase Polymerase Chain Reaction during the third trimester of pregnancy. Fundus examination found a unilateral hypopigmented retinal lesion, temporal to the macula, with an apex pointing to the fovea. Explorations in spectral-domain optical coherence tomography showed a subretinal cleft with broadening and attenuation of the interdigitation zone, elevation of the outer limiting membrane and the ellipsoid zone, without thinning of the outer retinal layers. CONCLUSION AND IMPORTANCE: There is a proven risk of congenital eye defects after Zika infection during pregnancy. We report here the first case of torpedo maculopathy without microcephaly, in a child suspected of maternal-fetal exposure to Zika.

Fovea Plana in a 9-Year-Old Boy Presenting with Decreased Vision in the Left Eye.

BACKGROUND Foveal hypoplasia (FH) is a congenital disorder, generally associated with other conditions. CASE REPORT A 9-year-old boy presented with moderately decreased vision in the left eye. Fundus examination showed an absence of macular reflection and no foveal pit was seen on optical coherence tomography. Fluorescein angiography demonstrated the absence of a foveal avascular zone. CONCLUSIONS This is a rare case of a unilateral fovea plana associated with a visual impairment.

Case Report: Orbital Tumor Revealing Adult T-Cell Leukemia/Lymphoma Associated with Human T-Cell Lymphotropic Virus Type-1.

Adult T-cell Leukemia/Lymphoma (ATLL) is a sight- and life-threatening complication of human T-cell lymphotropic virus type 1 (HTLV-1) infection. Ophthalmic manifestations include uveitis, optic nerve oedema, retinal vasculitis, and lymphomatous infiltration. Orbital lesions are rare. We report the case of an orbital tumor revealing systemic ATLL in a 45-year-old Dominican patient who died despite treatment. Apart from late-grade cutaneous T-cell lymphoma, ATLL is the only T-lymphoma to develop in the orbit. Diagnosis is based on serologic evidence of HTLV-1 infection, cytology, and blood sample analysis. Biopsy is deemed necessary. Given the poor prognosis of ATLL and the worldwide presentation of HTLV-1, physicians should consider ATLL in the differential diagnosis of orbital malignant tumor and look for HTLV-1 infection in populations at risk.

Temporal trends in Human T-Lymphotropic virus 1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP) incidence in Martinique over 25 years (1986-2010).

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) has been discovered in 1980 and has been linked to tropical spastic paraparesis (HAM/TSP) in 1985 in Martinique. There is no data on HAM/TSP incidence trends. We report, in the present work, the temporal trends incidence of HAM/TSP in Martinique over 25 years. METHODS: Martinique is a Caribbean French West Indies island deserved by a unique Neurology Department involved in HAM/TSP diagnosis and management. A registry has been set up since 1986 and patients diagnosed for a HAM/TSP were prospectively registered. Only patients with a definite HAM/TSP onset between 1986 and 2010 were included in the present study. The 25-year study time was stratified in five-year periods. Crude incidence rates with 95% confidence interval (95%CI) were calculated using Poisson distribution for each period. Age-standardized rates were calculated using the direct method and the Martinique population census of 1990 as reference. Standardized incidence rate ratios with 95% CIs and P trends were assessed from simple Poisson regression models. Number of HTLV-1 infection among first-time blood donors was retrospectively collected from the central computer data system of the Martinique blood bank. The HTLV-1 seroprevalence into this population has been calculated for four 5-year periods between 1996 and 2015. RESULTS: Overall, 153 patients were identified (mean age at onset, 53+/-13.1 years; female:male ratio, 4:1). Crude HAM/TSP incidence rates per 100,000 per 5 years (95%CI) in 1986-1990, 1991-1995, 1996-2000, 2001-2005 and 2006-2010 periods were 10.01 (6.78-13.28), 13.02 (9.34-16.70), 11.54 (8.13-14.95), 4.27 (2.24-6.28) and 2.03 (0.62-3.43). Age-standardized 5-year incidence rates significantly decreased by 69% and 87% in 2001-2005 and 2006-2010 study periods. Patients characteristics did not differ regarding 1986-2000 and 2001-2010 onset periods. Between 1996-2000 and 2011-2015 study periods, the HTLV-1 seroprevalence significantly decreased by 63%. CONCLUSION: Martinique faces a sudden and rapid decline of HAM/TSP incidence from 2001 in comparison to 1986-2000 periods. Reduction of HTLV-1 seroprevalence, that may result from transmission prevention strategy, could account for HAM/TSP incidence decrease.

Short delay to initiate plasma exchange is the strongest predictor of outcome in severe attacks of NMO spectrum disorders.

INTRODUCTION: Severe attacks of neuromyelitis optica spectrum disorder (NMO-SD) are improved by plasma exchange (PLEX) given as an adjunctive therapy. Initial studies failed to demonstrate a delay of PLEX treatment influenced clinical outcome; however PLEX was always used late. We examine the clinical consequences of delay in PLEX initiation on severe optic neuritis and spinal cord attacks in NMO-SD. METHODS: All of our patients who suffered attacks of NMO-SD, treated in our centre by PLEX, were retrospectively considered for inclusion. Primary outcome was defined as complete improvement. Secondary poor/good outcomes were respectively defined to be the higher/lower third of Delta-Expanded Disability Status Scale (EDSS) (late minus baseline EDSS). Delays from clinical onset to PLEX initiation were categorised for multivariate analysis. RESULTS: Of the 60 patients included, NMO-SD criteria (2015) were fulfilled in 92%. One hundred and fifteen attacks were included and received PLEX with a median of 7 days (0-54) after clinical onset. The probability to regain complete improvement continuously decreased from 50% for PLEX given at day 0 to 1%-5% after day 20. Through multivariate analysis, the baseline impairment and PLEX delay were associated with the probability to complete improvement (OR 5.3; 95% CI 1.8 to 15.9). Reducing the PLEX delay also influenced the good secondary outcome but not the poor secondary outcome. CONCLUSIONS: These results confirm an improved clinical benefit of early initiation of PLEX during severe attacks of NMO-SD. Perceiving PLEX as a rescue therapy only after steroid failure could be deleterious.

Retinal Nerve Fiber Layer Thickness in Human T-cell Lymphotropic Virus Type 1 Patients.

PURPOSE: To determine whether there is an optic neuropathy (ON) in patients with human T-cell lymphotropic virus type 1 (HTLV-1) infection. METHODS: We included HTLV-1 asymptomatic carriers (a.c.HTLV-1) and tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) patients between January 1st, 2014 and March 31st, 2015. All patients had complete eye examination. The visual acuity (VA) and retinal nerve fiber layer (RNFL) thickness were measured and compared to age- and sex-matched control groups including patients seen in our refraction clinic with no previous medical or surgical history. RESULTS: Thirty-one a.c.HTLV-1 (group 1) and 29 TSP/HAM patients (group 2) were included. The average RNFL thickness was 99.9 ± 14.3 µm in group 1 and 87.8 ± 19.2 µm in group 2. The average RFNL thicknesses were lower in both groups, when compared to controls. The difference was significant in patients with TSP/HAM (87.8 ± 19.2 µm vs. 97 ± 7.8 µm; p = 0.003) who also had significantly decreased VA. CONCLUSIONS: We report here the first study about the RNFL thickness in patients with TSP/HAM. In these patients, there is decrease of the RNFL thickness with subtle but definite decrease of VA. This suggests that subclinical ON occurs in the natural history of the disease. The diagnosis of TSP/HAM must be evoked as a differential of primary progressive multiple sclerosis in a population at risk. Moreover, RNFL thinning with no evidence of glaucoma should raise suspicion for HTLV-1 infection and TSP/HAM in a population at risk.

Endophthalmitis after cataract surgery despite intracameral antibiotic prophylaxis with licensed cefuroxime.

PURPOSE: To report a case series of post-phacoemulsification endophthalmitis despite antibiotic prophylaxis with an intracameral injection of a licensed cefuroxime formulation (Aprokam). SETTING: University Hospitals of Pointe-à-Pitre, Guadeloupe, and Fort-de-France, Martinique, French West Indies. DESIGN: Retrospective case series. METHODS: Patients who had cataract surgery with licensed cefuroxime prophylaxis between March 1, 2013, and July 31, 2015, and developed endophthalmitis were included. Bacteriologic findings and final corrected distance visual acuity 6 months after treatment were collected. RESULTS: Five patients developed endophthalmitis within 15 days after surgery, which was performed in different settings by different cataract surgeons. All patients had no-stich cataract surgery. Surgery was uneventful in 4 cases. One patient had a posterior capsule rupture. An anterior chamber paracentesis with analysis of the aqueous humor was performed to confirm endophthalmitis. Bacteriologic tests showed α-hemolytic streptococcus in 2 cases, Staphylococcus epidermidis in 1 case, and Serratia marcescens in 1 case. Two strains of bacteria showed cefuroxime resistance on the antibiogram. Despite parenteral and intravitreal injections of antibiotics, 4 of 5 cases had a poor outcome, with a visual acuity of less than 20/200. Retinal detachment (RD) was the most frequent complication observed in the following months. CONCLUSIONS: Although licensed cefuroxime has proven to be efficient in reducing the incidence of endophthalmitis, it has not eradicated this potentially severe complication of cataract surgery. Endophthalmitis occurring after the use of licensed cefuroxime can still result in very poor visual outcomes related to the infection itself or to its delayed complications such as RD. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Martinique Crinkled Retinal Pigment Epitheliopathy: Clinical Stages and Pathophysiologic Insights.

PURPOSE: To reappraise the autosomal dominant Martinique crinkled retinal pigment epitheliopathy (MCRPE) in light of the knowledge of its associated mutated gene mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3), an actor in the p38 mitogen-activated protein kinase pathway. DESIGN: Clinical and molecular study. PARTICIPANTS: A total of 45 patients from 3 generations belonging to a family originating from Martinique with an autosomal dominant MCRPE were examined. METHODS: Best-corrected visual acuity, fundus photographs, and spectral-domain optical coherence tomography (SD OCT) of all clinically affected patients and carriers for the causal mutation were reviewed at the initial visit and 4 years later for 10 of them. Histologic retinal lesions of Mapkapk3(-/-) mice were compared with those of the human disease. MAIN OUTCOME MEASURES: The MCRPE natural history in view of MAPKAPK3 function and Mapkapk3(-/-) mouse retinal lesions. RESULTS: Eighteen patients had the c.518T>C mutation. One heterozygous woman aged 20 years was asymptomatic with normal fundus and SD OCT (stage 0). All c.518T>C heterozygous patients older than 30 years of age had the characteristic dried-out soil fundus pattern (stages 1 and 2). Complications (stage 3) were observed in 7 cases, including polypoidal choroidal vasculopathy (PCV) and macular fibrosis or atrophy. One patient was homozygous and had a form with severe Bruch's membrane (BM) thickening and macular exudation with a dried-out soil pattern in the peripheral retina. The oldest heterozygous patient, who was legally blind, had peripheral nummular pigmentary changes (stage 4). After 4 years, visual acuity was unchanged in 6 of 10 patients. The dried-out soil elementary lesions radically enlarged in patients with a preferential macular extension and confluence. These findings are in line with the progressive thickening of BM noted with age in the mouse model. During follow-up, there was no occurrence of PCV. CONCLUSIONS: MCRPE is an autosomal dominant, fully penetrant retinal dystrophy with a preclinical stage, an onset after the age of 30 years, and a preserved visual acuity until occurrence of macular complications. The natural history of MCRPE is in relation to the role of MAPKAPK3 in BM modeling, vascular endothelial growth factor activity, retinal pigment epithelial responses to aging, and oxidative stress.

Third Cranial Nerve Palsy in the Setting of Chikungunya Virus Infection.

We report the case of a 62-year-old patient who developed an acute painless isolated left third cranial nerve palsy sparing the pupil in the setting of an acute chikungunya infection. The patient had no significant medical history. Specifically, he had no vascular risk factors. Ocular involvement in chikungunya fever is uncommon. The potential virus- and infection-related mechanisms of this third cranial nerve palsy are discussed.

A dominant mutation in MAPKAPK3, an actor of p38 signaling pathway, causes a new retinal dystrophy involving Bruch's membrane and retinal pigment epithelium.

Inherited retinal dystrophies are clinically and genetically heterogeneous with significant number of cases remaining genetically unresolved. We studied a large family from the West Indies islands with a peculiar retinal disease, the Martinique crinkled retinal pigment epitheliopathy that begins around the age of 30 with retinal pigment epithelium (RPE) and Bruch's membrane changes resembling a dry desert land and ends with a retinitis pigmentosa. Whole-exome sequencing identified a heterozygous c.518T>C (p.Leu173Pro) mutation in MAPKAPK3 that segregates with the disease in 14 affected and 28 unaffected siblings from three generations. This unknown variant is predicted to be damaging by bioinformatic predictive tools and the mutated protein to be non-functional by crystal structure analysis. MAPKAPK3 is a serine/threonine protein kinase of the p38 signaling pathway that is activated by a variety of stress stimuli and is implicated in cellular responses and gene regulation. In contrast to other tissues, MAPKAPK3 is highly expressed in the RPE, suggesting a crucial role for retinal physiology. Expression of the mutated allele in HEK cells revealed a mislocalization of the protein in the cytoplasm, leading to cytoskeleton alteration and cytodieresis inhibition. In Mapkapk3-/- mice, Bruch's membrane is irregular with both abnormal thickened and thinned portions. In conclusion, we identified the first pathogenic mutation in MAPKAPK3 associated with a retinal disease. These findings shed new lights on Bruch's membrane/RPE pathophysiology and will open studies of this signaling pathway in diseases with RPE and Bruch's membrane alterations, such as age-related macular degeneration.

RETINAL MANIFESTATIONS IN ADULT T-CELL LEUKEMIA/LYMPHOMA RELATED TO INFECTION BY THE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-1.

PURPOSE: To describe the retinal manifestations in adult T-cell leukemia (ATL) related to an infection by the human T-cell lymphotropic virus type-1 (HTLV-1). METHODS: Retrospective case series of patients with ATL with retinal findings. RESULTS: A total of 175 patients were diagnosed with ATL in Martinique between 1983 and 2013. Three of them showed intraocular findings related to ATL. They were bilateral deep retinal infiltrates associated with intermediate uveitis. In two cases, the ATL diagnosis was known. In the third, fluorescein angiography was remarkable for deep retinal infiltrates although fundus examination was unremarkable. The ATL cells were found in the blood of this patient. Despite chemotherapy, infiltrates progressed from the retinal periphery to the posterior pole in two patients, thus reducing visual acuity to light perception. They were associated with vasculitis. CONCLUSION: Retinal involvement in ATL is very rare. It can occur at any point during the natural course of the disease. Human T-cell lymphotropic virus type-1 carriers should benefit from a regular ophthalmic examination, and a fluorescein angiography must be performed in all patients with human T-cell lymphotropic virus type-1 with vitreous cells. The presence of deep retinal infiltrates must raise suspicion for ATL in a patient with human T-cell lymphotropic virus type-1.

Visual field characteristics in neuromyelitis optica in absence of and after one episode of optic neuritis.

PURPOSE: Optic neuritis (ON) observed during neuromyelitis optica (NMO) is in most cases very severe and with poor prognosis. This study's objective was to analyze visual field (VF) abnormalities observed in the absence of ON and post-ON episode. METHODS: Twenty-seven cases of both NMO and multiple sclerosis (MS) were selected. Thorough ophthalmologic exam was performed at least 6 months post-ON attack. The VF was collected using the Humphrey 750 perimeter. We used the central threshold tests 24-2 with FASTPAC strategy. The abnormalities were categorized based on the Optic Neuritis Treatment Trial classification. RESULTS: After one ON, 40% of the NMO group's eyes showed total VF loss (P = 0.01), 21% showed abnormalities of neurologic aspect, and 27% showed fascicular abnormalities of which 12% were altitudinal. Given the total VF loss, the positive predictive value in favor of an NMO was 92.8% and the negative predictive value was 47.3%. CONCLUSION: Alterations of the VF during the NMO differ from those observed in the course of the MS. One ON, blinding from the first attack, must call to mind an NMO. The altitudinal deficits point to a vascular mechanism.

Martinique (West Indies) crinkled retinal pigment epitheliopathy: clinical description.

PURPOSE: To report a previously undescribed pattern of crinkled retinal pigment epithelium (RPE), observed in a family of black patients originating from Martinique, an island in the French West Indies. METHODS: Three generations were examined by visual acuity measurement and fundus photography. Autofluorescence photography, fluorescein and indocyanine green angiography, visual field testing, electrophysiology, and spectral domain optical coherence tomography were performed in certain patients. RESULTS: One 86-year-old grandmother, her 7 children, her nephew, and 18 of her 22 grandchildren were examined. Nine patients were affected: five children, one nephew, and three grandchildren. An unrelated patient originating from the same area was also affected. In the third generation, fundus findings were whitish deep lines located in the posterior pole. Optical coherence tomography showed a crinkled pattern of a slightly elevated RPE. In the second generation, a scalloped crinkled RPE was observed in the posterior pole and midperiphery, giving an image of dry desert land in fluorescein and indocyanine green angiography. Optical coherence tomography showed that the RPE formed ripples, giving it a crinkled appearance. Complications were observed in six cases: they included RPE atrophy (one case), subretinal and sub-RPE hemorrhages because of polypoidal choroidal vasculopathy (four cases), and fibrovascular scarring (one case). The grandmother's fundi were characterized by peripheral pigmentary changes, with severe visual loss. CONCLUSION: The observed pattern appeared different from previously described dystrophies and could be referred to as Martinique crinkled retinal pigment epitheliopathy.

Efficacy of mitoxantrone in neuromyelitis optica spectrum: clinical and neuroradiological study.

OBJECTIVE: To evaluate the efficacy of mitoxantrone (MTX) on clinical and neuroradiological parameters of patients who had a relapse of neuromyelitis optica spectrum (NMOS) within the 12 previous months. METHODS: MTX (12 mg/m(2)) combined with methylprednisolone 1 g as three monthly courses followed by three quarterly courses was administered during an observational multicentre open study including 51 consecutive patients (28 NMO, 23 limited forms of NMO) of the French Caribbean and Guyana. The main outcome measure was the reduction of the annualised relapse rate (ARR), and the secondary outcome measures were alteration of disability measured by expanded disability status scale (EDSS) score, the time to onset of the first relapse, and the progression of neuroradiological lesions at 1 year of treatment. RESULTS: At 1 year of treatment, the ARR dropped from 1.82 to 0.37 (p<0.0001). The mean EDSS score improved by 1.3 points, going from 5.8 at baseline to 4.5 at 1 year (p<0.0001). The number of patients showing gadolinium (Gad)+ spinal cord lesions at baseline, that is, 46.9%, dropped to 10.6% (a 77.4% reduction; p=0.02). The median time to onset of the first relapse was 18 months. IgG-NMO seropositivity was a predictive factor of relapse (p=0.006). A case of acute myeloid leukaemia was observed after a mean time span of 4.8 years. CONCLUSIONS: In this observational NMO study, MTX decreased dramatically the frequency of relapses, which is directly related to progression of disability or even death in this disorder.

Treatment of optic neuritis by plasma exchange (add-on) in neuromyelitis optica.

OBJECTIVE: To assess the contribution of plasma exchange (PE) in association (add-on) with pulsed intravenous corticosteroids in acute optic neuritis of neuromyelitis optica (NMO) and limited forms of NMO. METHODS: Thirty-six patients with optic neuritis were treated from January 1, 1995, through December 31, 2010, with pulsed intravenous corticosteroids and 16 with pulsed intravenous corticosteroids plus PE. The ophthalmologic examination was performed at least 6 months after optic neuritis treatment. Visual acuity and visual field assessed with the Snellen scale and the logarithmic scale of the Early Treatment Diabetic Retinopathy Study were measured using standard automated perimetry and frequency doubling technology perimetry. Retinal peripapillary fiber thickness was measured using optical coherence tomography. RESULTS: Final visual acuity was 20/400 in the corticosteroid group and 20/50 in the PE group (P=.04). The gain in visual acuity was 20/200 in the corticosteroid group and 20/30 in the PE group (P=.01). A poor final visual acuity outcome (≤20/200) was found in 19 of 36 patients (53%) in the corticosteroid group and 2 of 16 patients (13%) in the PE group (P=.008). Mean (SD) thickness of peripapillary retinal nervous fibers was 63.1 (20.4) µm in the corticosteroid group and 70.3 (20.3) µm in the PE group (P=.16). The mean (SD) thickness in the temporal quadrant was 38.5 (14.1) µm in the corticosteroid group and 44.5 (12.7) µm in the PE group (P=.02). In multivariate analysis, PE treatment was the only independent factor associated with a visual acuity greater than 20/200. CONCLUSION: In optic neuritis associated with NMO, sequential treatment with pulsed intravenous corticosteroids and PE is more effective than standard monotherapy with corticosteroids on visual acuity outcome.