Low-level red-light therapy for myopia control in children: A systematic review and meta-analysis.

INTRODUCTION: Low-Level Red-Light (LLRL) Therapy is a safe and natural way to promote healing and reduce inflammation in the body. When it comes to treating myopia in children, LLRL therapy is recent, and its efficacy and safety still are not clear. METHODS: A systematic review and meta-analysis of the literature for LLRL was conducted in accordance with the PRISMA guidelines on November 5, 2022. Databases, including PUBMED, Cochrane Library, Web of Science, and Embase were queried. A meta-analysis of random effects was conducted. Inclusion criteria included Randomized Controlled Trials (RCTs) or observational studies where LLRL therapy was used in children (3‒15 years old) with myopia. Exclusion criteria were studies with other ocular abnormalities. Efficacy was evaluated through the mean change in Axial Length (AL) and cycloplegic Spherical Equivalent Error (SER), while safety was evaluated by monitoring adverse effects. RESULTS: A total of 5 final studies were included (4 RCTs, and 1 observational), in which 685 total patients were analyzed. The mean age was 9.7 ± 0.66 years, with 48,2% female patients. The number of eyes in the LRLL arm is 714 and, in the control, arm is 656. LLRL showed better results in SER and AL mean change (OR = 0.58; 95% CI 0.33 to 0.83; p < 0.00001, and MD -0.33; 95% CI -0.52 to -0.13; p = 0.001, respectively), in comparison to the control group. There was no significant difference in adverse effects between groups (MD = 5.76; 95% CI 0.66 to 50.14; p = 0.11). CONCLUSION: LLRL therapy is a non-invasive, effective, and safe short-term treatment option; however, long-term evaluation, particularly in comparison to other therapies, requires additional investigation.

Combined Endoscopic Cyclophotocoagulation and Phacoemulsification Versus Phacoemulsification Alone in the Glaucoma Treatment: A Systematic Review and Meta-Analysis.

The complete safety and efficacy of endoscopic cyclophotocoagulation (ECP) remain unclear in the literature and, to our knowledge, there are no current meta-analyses on phaco-ECP versus phacoemulsification alone to date. Thus, we conducted a systematic review and meta-analysis comparing these two strategies through studies, assessing the effectiveness and safety of outcomes in a population with glaucoma. The protocol for this systematic review was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42023482376). We systematically searched PubMed, Embase, and Web of Science from inception to December 2023. A random-effects model was used for all analyses due to heterogeneity. Review Manager 5.3 (Cochrane Centre, The Cochrane Collaboration, Denmark) was used for statistical analysis. Finally, nine studies were included in this comprehensive review and a total of 5389 eyes were analyzed in our study. In comparison to the ECP and phacoemulsification group, those receiving phacoemulsification alone showed better results in best-corrected visual acuity (MD 0.09; CI 95% 0.03 to 0.16; I²=0%), but worse outcomes in intraocular pressure (IOP) (MD -1.49; 95% CI -2.29 to -0.68; I²=29%) and use medications (MD -0.75; 95% CI -0.94 to -0.56; I²=0%) in the last visit. Complication rates, both general and serious, were significantly different between the groups, indicating the potential impact of combined procedures on patient outcomes. Thus, combining ECP with phacoemulsification for glaucoma treatment showed sustained IOP reduction and decreased medication dependence. However, higher complication rates suggest careful consideration of risks. More extensive research with larger trials and longer follow-ups is needed to validate findings and address limitations, providing valuable insights into this treatment approach.

Effects of aflibercept and bevacizumab on cell viability, cell metabolism and inflammation in hypoxic human Müller cells.

Anti-VEGF (vascular endothelial growth factor) drugs such as aflibercept (AFL) and bevacizumab (BVZ) inhibit pathological neo-angiogenesis and vascular permeability in retinal vascular diseases. As cytokines and growth factors are produced by Müller glial cells under stressful and pathological conditions, we evaluated the in vitro effect of AFL (Eylea®, 0.5 mg/mL) and BVZ (Avastin®, 0.5 mg/mL) on cell viability/metabolism, and cytokine/growth factor production by Müller cells (MIO-M1) under cobalt chloride (CoCl2)-induced hypoxia after 24h, 48h and 72h. Cell viability/metabolism were analyzed by Trypan Blue and MTT assays and cytokine/growth factors in supernatants by Luminex xMAP-based multiplex bead-based immunoassay. Cell viability increased with AFL at 48h and 72h and decreased with BVZ or hypoxia at 24h. BVZ-treated cells showed lower cell viability than AFL at all exposure times. Cell metabolism increased with AFL but decreased with BVZ (72h) and hypoxia (48h and72h). As expected, AFL and BVZ decreased VEGF levels. AFL increased PDGF-BB, IL-6 and TNF-α (24h) and BVZ increased PDGF-BB (72h). Hypoxia reduced IL-1ß, -6, -8, TNF-α and PDGF-BB at 24h, and its suppressive effect was more prominent than AFL (EGF, PDGF-BB, IL-1ß, IL-6, IL-8, and TNF-α) and BVZ (PDGF-BB and IL-6) effects. Hypoxia increased bFGF levels at 48h and 72h, even when combined with anti-VEGFs. However, the stimulatory effect of BVZ predominated over hypoxia for IL-8 and TNF-α (24h), as well as for IL-1ß (72h). Thus, AFL and BVZ exhibit distinct exposure times effects on MIO-M1 cells viability, metabolism, and cytokines/growth factors. Hypoxia and BVZ decreased MIO-M1 cell viability/metabolism, whereas AFL likely induced gliosis. Hypoxia resulted in immunosuppression, and BVZ stimulated inflammation in hypoxic MIO-M1 cells. These findings highlight the complexity of the cellular response as well as the interplay between anti-VEGF treatments and the hypoxic microenvironment.

Relationship between automated choroidal thickness measurements and retinal sensitivity using microperimetry in patients with myopia and different stages of myopic maculopathy.

PURPOSE: To assess the relationship between macular choroidal thickness (CT) measurements and retinal sensitivity (RS) in eyes with myopia and different stages of myopic maculopathy. METHODS: A masked, cross-sectional, and consecutive study involving patients with emmetropia/myopia (control group) and high myopia (HM) eyes. Automated choroidal thickness (CT) and manual outer retinal layer (ORL) thickness were acquired using swept-source optical coherence tomography, while retinal sensitivity (RS) assessed by microperimetry (MP3) in all regions of the macular Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Comparisons were made between groups, and correlations were performed among these measurements, demographic and ocular parameters and myopic maculopathy classification. RESULTS: A total of 37 (74 eyes) patients were included in the study. The mean age was 39 ± 13 years, and 28 patients (76%) were female. HM eyes exhibited inferior best-corrected visual acuity and a more advanced myopic maculopathy classification compared to the control group. The mean macular CT were 255 and 179 µm in the control and HM eyes (P < 0.001), respectively. In the HM eyes, superior ETDRS region presented the greatest values. Mean RS in control and HM groups was 28 and 24 dB (P = 0.001), respectively. Inner temporal followed by superior, were the regions of higher RS. Mean ORL thickness was 83 and 79 µm (P < 0.001), in the control and HM groups, respectively. The inner temporal ETDRS region presented the thickest measure. CT correlated significantly with RS (r = 0.41, P < 0.001) and ORL thickness, (r = 0.58, P < 0.001), which also correlated with RS (r = 0.40, P < 0.001). Spherical equivalent, axial length and myopic maculopathy stage were the parameters that most correlated with CT, RS and ORL thickness. For every 100 µm increase in thickening of CT there was an average increase of 3.4 µm in ORL thickness and 2.7 dB in RS. Myopic maculopathy classification demonstrated influence only with CT. CONCLUSION: Myopia degree is related to ORL and choroidal thinning and deterioration of retinal sensitivity in some ETDRS regions of the macula. Choroidal thinning is associated to with a decline of retinal sensitivity, thinning of ORL, and worsening of myopic maculopathy classification, so new treatments are necessary to prevent myopia progression.

Discrimination ability of central visual field testing using stimulus size I, II, and III and relationship between VF findings and macular ganglion cell thickness in chiasmal compression.

PURPOSE: To compare the relationship between macular ganglion cell layer (mGCL) thickness and 10-2 visual field (VF) sensitivity using different stimulus sizes in patients with temporal hemianopia from chiasmal compression. METHODS: A cross-sectional study was conducted involving 30 eyes from 25 patients with temporal VF loss on 24-2 SITA standard automated perimetry due to previous chiasmal compression and 30 healthy eyes (23 controls). Optical coherence tomography (OCT) of the macular area and 10-2 VF testing using Goldmann stimulus size I (GI), II (GII), and III (GIII) were performed in the Octopus 900 perimeter. For the sake of analysis, mGCL thickness and VF data were segregated into four quadrants (two temporal and two nasal) and two halves (temporal and nasal) centered on the fovea, in order to evaluate separately both the severely affected nasal hemi-retina corresponding to the temporal VF sectors and the subclinically affected temporal hemi-retina corresponding to the nasal VF sectors. Data from patients and controls were compared using generalized estimated equations. The discrimination ability of GI, GII, and GIII was evaluated, as was the correlation between mGCL and 10-2 VF sensitivity using GI, GII, and GIII. RESULTS: All mGCL parameters in the nasal and temporal halves of the retina were significantly reduced in patients compared to controls. 10-2 VF test sensitivity using GI, GII, and GIII was significantly lower in patients than in controls (p≤0.008) for all parameters, except the three nasal divisions when using GI (p = 0.41, 0.07 and 0.18) Significant correlations were found between temporal VF sectors (all stimulus sizes) and the corresponding nasal mGCL measurements, with similar discrimination ability. Significant correlations were also observed between all three nasal VF divisions and the corresponding temporal mGCL thickness when using stimulus sizes I and II, but not stimulus size III. CONCLUSIONS: On 10-2 VF testing, GII outperformed GI and GIII with regard to discrimination ability and structure-function correlation with mGCL thickness in the subclinically affected nasal part of the VF in patients with chiasmal compression. Our findings suggest that the use of GII can enhance the diagnostic power of 10-2 VF testing in early cases of chiasmal compression, although further studies are necessary to support this conclusion.

Correlation between retinal sensitivity assessed by microperimetry and structural abnormalities on optical coherence tomography after successful epiretinal membrane surgery.

BACKGROUND: To verify the correlation between retinal sensitivity (RS) assessed by the microperimetry (MP) and optical coherence tomography (OCT) parameters measured in eyes submitted to pars-plana vitrectomy (PPV) for idiopathic epiretinal membrane (ERM) treatment. METHODS: 43 patients underwent PPV. Best-corrected visual acuity (BCVA) and OCT imaging were acquired preoperatively and 6 months after surgery. The RS values were recorded 6 months after the surgery. Total macular thickness (TMT) measurements and OCT-evaluated structural findings were also analyzed. The MP examination tested 44 points, with direct topographic correspondence with the OCT-ETDRS map. Correlations between BCVA, RS, and OCT parameters were assessed. RESULTS: TMT measurements in patients were significantly thicker preoperatively and reduced after surgery. All patients demonstrated BCVA improvements after surgery. The RS parameters after surgery were significantly lower in patients. For OCT structural analyses, patients with lower RS at the fovea correlated with the preexisting disorganization of retinal inner layers (DRIL). In addition, lower RS values were associated with DRIL, outer retinal changes (ORC), and intraretinal microcysts after surgery. CONCLUSIONS: The RS values after surgery were significantly lower when compared to controls. The DRIL presence before and after surgery, and microcysts and ORC after surgery were related to worse visual outcomes.

Surgical management of retinal detachment and macular holes secondary to ocular toxoplasmosis: a systematic review and meta-analysis.

BACKGROUND: Toxoplasma gondii causes ocular toxoplasmosis (OT), involving inflammation, scarring, and retinal complications. The OT complications were retinal detachment (RD), and retinal breakage (RB). Surgical interventions like scleral buckling (SB) and vitrectomy are common. Limited understanding exists of the safety and efficacy of surgical management of RD/RB secondary to OT. Another complication is toxoplasmosis-related macular holes (tMH), with sparse evidence on surgical outcomes. This meta-analysis aims to clarify clinical characteristics, and surgical results, and enhance understanding of RD, RB, and MH secondary to OT. METHODS: PubMed, Cochrane, Embase and Web of Science database were queried for retrospective studies, case series and case reports that provided information on RD, RB and MH associated with OT and reported the outcomes of: (1) Retinal reattachment of RD/RB and tMH closure; (2) Best-corrected visual acuity (BCVA) improvement; and (3) Complications. Heterogeneity was examined with I2 statistics. A random-effects model was used for outcomes with high heterogeneity. Statistical analysis was performed using the software R (version 4.2.3, R Foundation for Statistical Computing, Vienna, Austria). RESULTS: Fourteen final studies, comprising a total of 96 patients were analyzed, 81 with RD or RB and 15 with tMH. Overall, surgical management was associated with several advantages: a high rate of retinal reattachment of RD/RB of 97% (95% Confidence Interval [CI] 92-100%; I2 = 0%), retinal reattachment of just RD of 96% (95% CI 89-100%; I2 = 30%) and tMH closure 97% (95% CI 87-100; I2 = 12%). There were significant differences in BCVA after surgeries in studies of RD/RB (MD 0.60; 95% CI 0.35-0.65; I2 = 20%) and MH (MD 0.67; 95% CI 0.50-0.84; I2 = 0%). The overall complication rate associated with surgical procedures in RD/RB secondary to OT was confirmed to be 25%. CONCLUSIONS: The systematic review and meta-analysis showed that the treatment approaches currently in use are effective, with a remarkable rate of retinal reattachment of RD/RB, tMH closure, and substantial improvements in visual acuity. More randomized, long-term studies on disease and surgical factors can provide valuable insights into their impact on anatomical and visual outcomes.

Optical coherence tomography detection of retinal neural loss in patients with tuberous sclerosis.

PURPOSE: Tuberous Sclerosis (TS) is a rare, multisystem genetic disease caused by mutations in the TSC1 and TSC2 genes, leading to abnormalities in cell differentiation and proliferation. This study aimed to evaluate the neural integrity of individuals with TS by using Optical Coherence Tomography (OCT) to examine the peripapillary retinal nerve fiber layer (RNFL) thickness and the macular thickness in patients with TS and to compare with healthy controls. METHODS: Peripapillary and macular OCT scans (Optopol Revo NX SD OCT) were performed on 41 eyes from 22 TS patients, divided into two groups based on the presence of retinal hamartomas, and compared to 20 eyes from a control group. The average peripapillary RNFL thickness was measured for each quadrant. The macular total thickness and ganglion cell layer (GCL) + inner plexiform layer (IPL) thickness were measured based on the Early Treatment Diabetic Retinopathy Study (ETDRS) map. All measurements were then compared between the groups and controls. RESULTS: The TS group showed significantly reduced RNFL thickness and macular thickness when compared to the control group. Specifically, patients with retinal hamartomas exhibited an even more pronounced thinning of both RNFL and macular thickness. CONCLUSIONS: These findings suggest that TS patients undergo significant changes in retinal neurodevelopment and experience axonal loss. This finding may have significant prognostic utility regarding central nervous system degeneration in TS, particularly among patients with retinal hamartomas. OCT may serve as a valuable tool for assessing axonal structural abnormalities in TS patients. TRIAL REGISTRATION NUMBER: Not applicable.

Retinoblastoma treatment in a Brazilian population. Presentation and long-term results.

INTRODUCTION: Retinoblastoma is a malignant tumor with a high cure potential when proper therapy is used. The purpose of this paper is to report the clinical features and outcomes of patients with retinoblastoma who were treated with a combination of local and systemic chemotherapy-based protocols. METHOD: We retrospectively studied patients treated with systemic chemotherapy plus local treatment between 2003 and 2015 with a follow-up ≥2 years. We correlated clinical and pathological characteristics with decimal visual acuity (VA) and death. RESULTS: Among 119 patients, 60% had unilateral disease (UNI), and 52% were male. The median presentation age was 19.5 months, 10% had a positive family history, and the most frequent sign was leukocoria (68.8%). Advanced disease was more frequent in eyes with UNI (98.4%) than in eyes with bilateral retinoblastoma (BIL: 55.3%). Enucleation was performed in 97% of UNI eyes and in 55.8% of BIL eyes. The overall globe salvage was 26.6%, 44.25% of BIL eyes. Bilateral enucleation was required in 5%. High-risk pathologic features occurred in 50% and 37% of eyes enucleated without and with neoadjuvant chemotherapy, respectively. High-risk features were related to the presence of goniosynechiae in the pathologic specimen and were more frequent in children younger than 10 months or older than 40 months. Extraocular disease was present in 5% of patients, and the death rate related to metastasis of the tumor was 8%. The final VA was ≥ 0.7 in 72.8% and ≥0.1 in 91% of BIL patients. CONCLUSIONS: Treatment of retinoblastoma with conservative systemic-based chemotherapy was associated with an excellent survival rate (92%). Albeit the low overall globe salvage rate, in BIL patients, approximately half the eyes were conserved, and a satisfactory functional visual result was achieved The evaluated protocol is an important treatment option, especially in developing countries.

Methodology and Experimental Protocol for Studying Learning and Motor Control in Neuromuscular Structures in Pilates.

The benefits of Pilates have been extensively researched for their impact on muscular, psychological, and cardiac health, as well as body composition, among other aspects. This study aims to investigate the influence of the Pilates method on the learning process, motor control, and neuromuscular trunk stabilization, specifically in both experienced and inexperienced practitioners. This semi-randomized controlled trial compares the level of experience among 36 Pilates practitioners in terms of motor control and learning of two Pilates-based skills: standing plank and side crisscross. Data will be collected using various assessment methods, including abdominal wall muscle ultrasound (AWMUS), shear wave elastography (SWE), gaze behavior (GA) assessment, electroencephalography (EEG), and video motion. Significant intra- and inter-individual variations are expected, due to the diverse morphological and psychomotor profiles in the sample. The adoption of both linear and non-linear analyses will provide a comprehensive evaluation of how neuromuscular structures evolve over time and space, offering both quantitative and qualitative insights. Non-linear analysis is expected to reveal higher entropy in the expert group compared to non-experts, signifying greater complexity in their motor control. In terms of stability, experts are likely to exhibit higher Lyapunov exponent values, indicating enhanced stability and coordination, along with lower Hurst exponent values. In elastography, experienced practitioners are expected to display higher transversus abdominis (TrA) muscle elasticity, due to their proficiency. Concerning GA, non-experts are expected to demonstrate more saccades, focus on more Areas of Interest (AOIs), and shorter fixation times, as experts are presumed to have more efficient gaze control. In EEG, we anticipate higher theta wave values in the non-expert group compared to the expert group. These expectations draw from similar studies in elastography and correlated research in eye tracking and EEG. They are consistent with the principles of the Pilates Method and other scientific knowledge in related techniques.

Morphofunctional evaluation of peripapillary retinoschisis associated with myopic posterior staphyloma and hyaloid traction: does it cause peripapillary vitreoretinal traction? / Avaliação morfofuncional da retinosquise peripapilar associada ao estafloma posterior miópico e à tração hialoidea: isso causa tração vitreo-retiniana peripapilar?

ABSTRACT This case report presents the details of a 33-year-old female patient who was referred to a specialized retina service because of mild vision loss in her right eye). The patient's visual acuity was 20/25 in right eye and 20/50 in the left eye (; amblyopic); the spherical equivalent was -12.75 diopters (right eye) and -14.75 diopters (left eye). Multimodal retinal imaging showed peripapillary schisis in both the inner and outer retinal layers, grade II posterior vitreous detachment, and a tessellated fundus. Using Humphrey perimetry and MP-3 microperimetry, the functional evaluation indicated macular sensitivity within normal limits and decreased sensitivity in the peripapillary region, especially in right eye. The pattern-re versal visual evoked potential was measured. The N75 and P100 latency and amplitude in right eye were within normal values for checks of 1º. However, the amplitude was low for checks of 15′. Highly myopic patients who have posterior staphyloma that involves the optic nerve are susceptible to posterior hyaloid traction, and the resulting peripapillary vitreous traction may compromise vision.

RESUMO Este relato de caso apresenta um paciente feminino de 33 anos encaminhado para um serviço especializado de retina devido à leve perda de visão em olho direito. A acuidade visual foi de 20/25 no olho direito e 20/50 no olho esquerdo, o equivalente esférico foi de -12,75 dioptrias e -14,75 dioptrias, respectivamente. Avaliações multimodais revelaram isquese peripapilar nas camadas internas e externas da retina, descolamento vítreo posterior grau II e fundo tesselado. Avaliação funcional com perimetria Humphrey e microperimetria MP-3 revelaram sensibilidade macular normais e diminuição da sensibilidade na região peripapilar, especialmente no olho direito. Potencial visual evocado de padrão reverso apresentou no olho direito latência e amplitude N75 e P100 dentro dos valores normais para verificação de 1º. Entretanto, a amplitude foi baixa para a de 15′. Pacientes alto míopes com esfiloma posterior envolvendo o nervo óptico são suscetíveis à tração da hialoide posterior. Portanto a tração vitreopapilar resultante pode causar comprometimento da visão.

Normative data for macular perimetry using the MP-3 microperimeter in healthy individuals / Dados normativos para perimetria macular usando o microperímetro MP-3 em indivíduos normais

ABSTRACT Purpose: Microperimetry has been used for several years as a form of visual function testing in patients with retinal diseases. Normal microperimetry values obtained with microperimeter MP-3 have not yet been fully published, and baseline values for topographic macular sensitivity and correlations with age and sex are needed to establish degrees of impairment. This study aimed to determine values for light sensitivity thresholds and fixation stability using the MP-3 in healthy individuals. Methods: Thirty-seven healthy volunteers (age, 28-68 years), underwent full-threshold microperimetry using a 4-2 (fast) staircase strategy with the standard Goldmann III stimulus size and 68 test points positioned identically to those in the Humphrey Field Analyzer 10-2 test grid. The fixation stability was simultaneously recorded during the microperimetry test. The relationship between global sensitivity and age was calculated using linear regression analysis. Results: Microperimetry was performed on 37 participants (74 eyes). The global mean sensitivity was 29.01 ± 1.44 (range, 26-31) dB. The mean central sensitivity at 2° measured by the MP-3 was 28.5 ± 1.77 dB in the right eye (OD) and 28.75 ± 1.98 dB in the left eye (OS). The total median fixation stability values within 2° and 4° were 80% and 96%, respectively. The linear regression analysis also revealed an age-related global sensitivity decline per year of -0.051 dB ± 0.018 (OD) and -0.078 dB ± 0.021 (OS). Conclusions: Microperimetry performed with the MP-3 allows for an automatic, accurate, and topography-specific examination of retinal sensitivity thresholds. The results of this study provide a normal and age-matched database of MP-3 microperimetry.

RESUMO Objetivos: A microperimetria tem sido usada há vários anos como uma forma de teste de função visual em pacientes com doenças da retina. Os valores normais de microperimetria obtidos com MP-3 ainda não foram totalmente publicados e os valores basais para sensibilidade macular topográfica e correlações com idade e sexo são necessários para estabelecer graus de comprometimento. O objetivo do trabalho é determinar valores para limiares de sensibilidade à luz e estabilidade de fixação usando o MP-3 em indivíduos normais. Métodos: Trinta e sete voluntários saudáveis (idade: 28-68 anos), submetidos à microperimetria de limiar total usando uma estratégia de escada 4-2 (rápida) com o tamanho de estímulo padrão Goldmann III e 68 pontos de teste posicionados de forma idêntica aos do Humphrey Field Analyzer 10-2 grade de teste. A estabilidade da fixação foi registrada simultaneamente durante o teste de microperimetria. A relação entre a sensibilidade global e a idade foi calculada por meio de análise de regressão linear. Resultados: A microperimetria foi realizada em 37 indivíduos (74 olhos). A sensibilidade média global foi de 29,01 ± 1,44 dB, intervalo: 26-31 dB. A mediana da sensibilidade central a 2° medida pelo MP-3 foi de 28,5 ± 1,77 dB (ER) e 28,75 ± 1,98 dB (OE). Os valores médios totais de estabilidade da fixação em 2° e 4° foram 80% e 96%, respectivamente. A análise de regressão linear também revelou um declínio de sensibilidade global relacionado à idade por ano de -0,051 dB ± 0,018 (ER) e -0,078 dB ± 0,021 (LE). Conclusões: A microperimetria realizada com o MP-3 permite um exame automático, preciso e específico da topografia dos limiares de sensibilidade da retina. Os resultados deste estudo fornecem um banco de dados normal e de idade correspondente da microperimetria MP-3.

Immunoglobulin A Antibodies Against Myelin Oligodendrocyte Glycoprotein in a Subgroup of Patients With Central Nervous System Demyelination.

Importance: Differential diagnosis of patients with seronegative demyelinating central nervous system (CNS) disease is challenging. In this regard, evidence suggests that immunoglobulin (Ig) A plays a role in the pathogenesis of different autoimmune diseases. Yet little is known about the presence and clinical relevance of IgA antibodies against myelin oligodendrocyte glycoprotein (MOG) in CNS demyelination. Objective: To investigate the frequency of MOG-IgA and associated clinical features in patients with demyelinating CNS disease and healthy controls. Design, Setting, and Participants: This longitudinal study comprised 1 discovery and 1 confirmation cohort derived from 5 centers. Participants included patients with suspected or confirmed demyelinating diseases and healthy controls. MOG-IgA, MOG-IgG, and MOG-IgM were measured in serum samples and cerebrospinal fluid (CSF) of patients, who were assessed from September 2012 to April 2022. Main Outcomes and Measures: Frequency and clinical features of patients who were seropositive for MOG-IgA and double-seronegative for aquaporin 4 (AQP4) IgG and MOG-IgG. Results: After the exclusion of 5 participants with coexisting AQP4-IgG and MOG-IgA, MOG-IgG, and/or MOG-IgM, 1339 patients and 110 healthy controls were included; the median follow-up time was 39 months (range, 0-227 months). Of included patients with isolated MOG-IgA, 11 of 18 were female (61%), and the median age was 31.5 years (range, 3-76 years). Among patients double-seronegative for AQP4-IgG and MOG-IgG (1126/1339; 84%), isolated MOG-IgA was identified in 3 of 50 patients (6%) with neuromyelitis optica spectrum disorder, 5 of 228 patients (2%) with other CNS demyelinating diseases, and 10 of 848 patients (1%) with multiple sclerosis but in none of the healthy controls (0/110). The most common disease manifestation in patients seropositive for isolated MOG-IgA was myelitis (11/17 [65%]), followed by more frequent brainstem syndrome (7/16 [44%] vs 14/75 [19%], respectively; P = .048), and infrequent manifestation of optic neuritis (4/15 [27%] vs 46/73 [63%], respectively; P = .02) vs patients with MOG-IgG. Among patients fulfilling 2017 McDonald criteria for multiple sclerosis, MOG-IgA was associated with less frequent CSF-specific oligoclonal bands (4/9 [44%] vs 325/351 [93%], respectively; P < .001) vs patients with multiple sclerosis who were MOG-IgG/IgA seronegative. Further, most patients with isolated MOG-IgA presented clinical attacks after recent infection or vaccination (7/11 [64%]). Conclusion and Relevance: In this study, MOG-specific IgA was identified in a subgroup of patients who were double-seronegative for AQP4-/MOG-IgG, suggesting that MOG-IgA may be a novel diagnostic biomarker for patients with CNS demyelination.

Paracentral Acute Middle Maculopathy Associated with Severe Anti-Mog (Myelin Oligodendrocyte Glycoprotein)-Positive Optic Neuritis.

Retinal complications in patients with inflammatory optic neuritis (ON) are generally related to post-infectious neuroretinitis and are considered uncommon in autoimmune/demyelinating ON, whether isolated or caused by multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). More recently, however, cases with retinal complications have been reported in subjects positive for myelin oligodendrocyte glycoprotein (MOG) antibodies. We report a 53-year-old woman presenting with severe bilateral ON associated with a focal area of paracentral acute middle maculopathy (PAMM) in one eye. Visual loss recovered remarkably after high-dose intravenous corticosteroid treatment and plasmapheresis, but the PAMM lesion remained visible on both optical coherence tomography and angiography as an ischaemic lesion affecting the middle layers of the retina. The report emphasises the possible occurrence of retinal vascular complications in MOG-related optic neuritis, an important addition to the diagnosis of, and possible differentiation from, MS-related or NMOSD-related ON.

Optic Nerve Sheath Fenestration as Adjuvant Treatment for Severe Pseudotumor Cerebri Syndrome Induced by All-Trans Retinoic Acid.

All-trans retinoic acid (ATRA) is a vitamin A derivative which can increase intracranial pressure, causing visual loss and papilledema. Those patients should be treated similarly to others patients with idiopathic intracranial hypertension. We described a case of a 32-year-old woman presenting with severe visual loss and intracranial hypertension induced by ATRA for acute promyelocytic leukemia, which was treated clinically and with optic nerve sheath fenestration. Patients receiving ATRA therapy should be monitored to neurological and ophthalmic signs and symptoms of intracranial hypertension.

Real-world application of the 2022 diagnostic criteria for first-ever episode of optic neuritis.

Optic neuritis (ON) admits diverse differential diagnoses. Petzold proposed diagnostic criteria for ON in 2022, although real-world application of these criteria is missing. We conducted a retrospective review of patients with ON. We classified patients into definite or possible ON, and into groups A (typical neuritis), B (painless), or C (binocular) and estimated the frequency of etiologies for each group. We included 77 patients, with 62% definite and 38% possible ON. CRION and NMOSD-AQP4 negative-ON were less commonly seen in definite ON. Application of the 2022 criteria revealed a lower-than-expected frequency of definite ON, particularly for seronegative non-MS causes.

A comparative study of visual outcome in patients with optic neuritis treated with five or seven days of intravenous corticosteroid treatment.

BACKGROUND: Optic neuritis (ON), a major cause of visual impairment in young adults, is generally associated with rapid visual recovery when treated with intravenous methylprednisolone treatment (IVMPT). However, the optimal duration of such treatment is unknown, ranging from three to seven days in clinical practice. We aimed to compare the visual recovery in patients treated with 5-day or 7-day duration IVMPT. METHODS: We performed a retrospective cohort study of consecutive patients with ON in São Paulo, Brazil, from 2016 to 2021. We compared the proportion of participants with visual impairment in 5-day and 7-day treatment schedules at discharge, at 1 month and between 6 and 12 months after the diagnosis of ON. The findings were adjusted to age, severity of the visual impairment, co-intervention with plasma exchange, time from symptom onset to IVMPT and the etiology of the ON to mitigate indication bias. RESULTS: We included 73 patients with ON treated with 5 or 7-day duration of 1 g/d intravenous methylprednisolone therapy. Visual impairment at 6-12 months in the 5-day or the 7-day treatment groups was similar (57% x 59%, p > 0.9, Odds Ratio 1.03 [95% CI 0.59-1.84]). The results were similar after adjusting for prognostic variables and when observed at different time points. CONCLUSION: Visual recovery is similar in patients treated with 5-day and 7-day duration treatments of 1 g/day intravenous methylprednisolone, suggesting a ceiling effect. Limiting the duration of the treatment can reduce hospital stay and costs, without interfering with clinical benefit.

Ocular retinal findings in asymptomatic patients with antiphospholipid syndrome secondary to systemic lupus erythematosus.

The objective is to perform a multimodal ophthalmological evaluation, including optical coherence angiography (OCTA), asymptomatic APS secondary to SLE (APS/SLE), and compare to SLE patients and control group (CG). We performed a complete structural/functional ophthalmological evaluation using OCTA/microperimetry exam in all participants. One hundred fifty eyes/75 asymptomatic subjects [APS/SLE (n = 25), SLE (n = 25), and CG (n = 25)] were included. Ophthalmologic abnormalities occurred in 9 (36%) APS/SLE, 11 (44%) SLE, and none of CG (p < 0.001). The most common retinal finding was Drusen-like deposits (DLDs) exclusively in APS/SLE and SLE (16% vs. 24%, p = 0.75) whereas severe changes occurred solely in APS/SLE [2 paracentral acute middle maculopathy (PAMM) and 1 homonymous quadrantanopsia]. A trend of higher frequency of antiphospholipid antibody (aPL) triple positivity (100% vs. 16%, p = 0.05) and higher mean values of adjusted Global Antiphospholipid Syndrome Score (aGAPSS) (14 ± 0 vs. 9.69 ± 3.44, p = 0.09) was observed in APS/SLE with PAMM vs. those without this complication. We identified that ophthalmologic retinal abnormalities occurred in more than 1/4 of asymptomatic APS/SLE and SLE. DLDs are the most frequent with similar frequencies in both conditions whereas PAMM occurred exclusively in APS/SLE patients. The possible association of the latter condition with aPL triple positivity and high aGAPSS suggests these two conditions may underlie the retinal maculopathy. Our findings in asymptomatic patients reinforce the need for early surveillance in these patients. Key Points • Retinal abnormalities occur in more than 1/4 of asymptomatic APS/SLE and SLE patients. • The occurrence of PAMM is possibly associated with APS and DLDs with SLE. • Presence of aPL triple positivity and high aGAPSS seem to be risk factors for PAMM.

Normative data for macular perimetry using the MP-3 microperimeter in healthy individuals.

PURPOSE: Microperimetry has been used for several years as a form of visual function testing in patients with retinal diseases. Normal microperimetry values obtained with microperimeter MP-3 have not yet been fully published, and baseline values for topographic macular sensitivity and correlations with age and sex are needed to establish degrees of impairment. This study aimed to determine values for light sensitivity thresholds and fixation stability using the MP-3 in healthy individuals. METHODS: Thirty-seven healthy volunteers (age, 28-68 years), underwent full-threshold microperimetry using a 4-2 (fast) staircase strategy with the standard Goldmann III stimulus size and 68 test points positioned identically to those in the Humphrey Field Analyzer 10-2 test grid. The fixation stability was simultaneously recorded during the microperimetry test. The relationship between global sensitivity and age was calculated using linear regression analysis. RESULTS: Microperimetry was performed on 37 participants (74 eyes). The global mean sensitivity was 29.01 ± 1.44 (range, 26-31) dB. The mean central sensitivity at 2° measured by the MP-3 was 28.5 ± 1.77 dB in the right eye (OD) and 28.75 ± 1.98 dB in the left eye (OS). The total median fixation stability values within 2° and 4° were 80% and 96%, respectively. The linear regression analysis also revealed an age-related global sensitivity decline per year of -0.051 dB ± 0.018 (OD) and -0.078 dB ± 0.021 (OS). CONCLUSIONS: Microperimetry performed with the MP-3 allows for an automatic, accurate, and topography-specific examination of retinal sensitivity thresholds. The results of this study provide a normal and age-matched database of MP-3 microperimetry.

Structure and synthesis of a vaccine and diagnostic target for Enterocloster bolteae, an autism-associated gut pathogen - Part II.

Enterocloster bolteae (formerly known as Clostridium bolteae) is a gastro-intestinal pathogenic bacterium often detected in the fecal microbiome of children in the autism spectrum. E. bolteae excretes metabolites that are thought to act as neurotoxins. This study is an update of our first E. bolteae investigation that discovered an immunogenic polysaccharide. Through a combination of chemical derivatizations/degradations, spectrometry and spectroscopy techniques, a polysaccharide composed of disaccharide repeating blocks comprised of 3-linked ß-d-ribofuranose and 4-linked α-l-rhamnopyranose, [→3)-ß-D-Ribf-(1 â†’ 4)-α-L-Rhap-(1→]n, was identified. To confirm the structure, and to provide material for subsequent investigations, the chemical synthesis of a corresponding linker-equipped tetrasaccharide, ß-D-Ribf-(1 â†’ 4)-α-L-Rhap-(1 â†’ 3)-ß-D-Ribf-(1 â†’ 4)-α-L-Rhap-(1→O(CH2)8N3, is also described. Research tools based on this immunogenic glycan structure can form the foundation for serotype classification, diagnostic/vaccine targets and clinical studies into the hypothesized role of E. bolteae in the onset/augmentation of autism related conditions in children.