Prevalence and Risk Factors for Metamorphopsia after Successful Retinal Detachment Surgery.

INTRODUCTION: The aim of the study was to determine the prevalence of metamorphopsia following rhegmatogenous retinal detachment (RRD) surgery, as well as associated predictive factors. METHODS: A total of 107 eyes successfully operated for RRD underwent metamorphopsia severity assessment using M-CHARTS, and foveal microstructure analysis by spectral domain optical coherence tomography, at 1 and 6 months postoperatively. Univariate and multivariate logistic regression rendered evaluation of preoperative risk factors. The correlation between metamorphopsia score and outer retinal layer (ORL) integrity was investigated and preoperative risk factors evaluated. RESULTS: The prevalence of postoperative metamorphopsia decreased from 51.4 to 29.9% and the median metamorphopsia score significantly improved (0.5, 95% CI: 0.3; 0.9, to 0.2, 95% CI: 0; 0.5, p < 0.001) from 1 to 6 months, respectively. Preoperative macular detachment was the only predictor found (OR 11.0, 95% CI: 3.1; 39.4, p < 0.001). Metamorphopsia severity was significantly associated with outer nuclear layer thickness and the status of the ellipsoid and cone interdigitation zones. One-month M-CHARTS had 81% sensitivity and 87% specificity in predicting full metamorphopsia recovery at 6 months (0.45 cut-off score). CONCLUSION: The prevalence of metamorphopsia decreased in parallel to ORL restoration, thus demonstrating the etiological role of photoreceptor-level morphological changes. M-CHARTS allowed for monitoring and predicting metamorphopsia recovery after RRD.

Intravitreal Injection of Bevacizumab for the Prevention of Postoperative Proliferative Vitreoretinopathy in High-Risk Patients Selected by Laser Flare Photometry.

INTRODUCTION: To evaluate the effect of an intravitreal injection of bevacizumab at the time of rhegmatogenous retinal detachment (RRD) surgery, on postoperative proliferative vitreoretinopathy (PVR) in high-risk patients selected by laser flare photometry. METHODS: This single-center observational retrospective cohort study included 137 consecutive patients who underwent pars plana vitrectomy and gas tamponade for primary RRD with increased aqueous flare between July 2016 and June 2021. From June 2019, an intravitreal injection of bevacizumab was administered as an adjunct to RRD repair. Patients who underwent surgery before this time and who did not receive intravitreal bevacizumab served as controls. The main outcome was the rate of retinal redetachment due to PVR. RESULTS: The median flare value was 22.0 (16.5-36.5) pc/ms in the control group and 28.2 (19.7-41.0) pc/ms in the bevacizumab group (p = 0.063). Eyes treated with bevacizumab were more likely to have macula-off RRD (p = 0.003), grade B PVR (p = 0.038), and worse visual acuity (p = 0.004) than controls. The rate of PVR redetachment was significantly lower in the bevacizumab group (11.1%) than in the control (30.1%) (p = 0.012). This difference was more pronounced after adjusting for potential confounding factors (p = 0.005); the risk of developing PVR was 4.5-fold higher in controls (95% CI, 1.6-12.8). After adjustment, the final median visual acuity was also significantly higher in eyes treated with bevacizumab (p = 0.025). CONCLUSION: This pilot study provides preliminary evidence that bevacizumab may reduce the risk of PVR-related recurrent RRD and improve visual outcomes in high-risk patients selected by laser flare photometry.

Effect of Duration of Silicone Oil Tamponade on Retinal Structure after Rhegmatogenous Retinal Detachment Surgery.

PURPOSE: The aim of the study was to investigate the effect of tamponade duration on retinal changes induced by silicone oil (SO) in patients who underwent successful rhegmatogenous retinal detachment (RRD) surgery. METHODS: Retrospective comparative case series of 68 patients who underwent SO tamponade for RRD. Patients were divided into 2 groups based on timing of SO removal: <6 months (group 1, n = 34) versus ≥6 months (group 2, n = 34). The main outcome measure was the change in central macular, inner, and outer retinal layer thickness (CMT, IRLT, and ORLT) before and after SO removal (SOR). RESULTS: The median tamponade duration was 4 [Clin Ophthalmol. 2016;10:471-6, Zhonghua Yan Ke Za Zhi. 1997 Jan;33(1):39-41] months in group 1 and 8 [Arch Ophthalmol. 1994 Jun;112(6):778-85, Retina. 2004 Dec;24(6):871-7] months in group 2 (p < 0.001). The mean CMT significantly increased from 245.3 ± 22.2 µm and 238.8 ± 41.6 µm under SO to 281.3 ± 60.2 µm and 259.0 ± 43.5 µm after SOR in group 1 (p = 0.009) and in group 2 (p = 0.007), respectively. Automated segmentation measurement revealed a significant increase in mean IRLT (p = 0.014 and p = 0.013) but no change in mean ORLT (p = 0.080 and p = 0.257) in both groups. After adjustment, there was no difference between the 2 groups in terms of mean final CMT, IRLT, and ORLT and mean retinal thickness changes after SOR. There was also no correlation between the tamponade duration and macular microstructural changes or visual recovery. CONCLUSION: SO tamponade causes a thinning of all retinal layers, mainly affecting the inner retinal layer. However, these changes resolved following SO extraction and were not affected by longer tamponade duration.

Intravenous high-dose methotrexate based systemic therapy in the treatment of isolated primary vitreoretinal lymphoma: An LOC network study.

The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011 and 2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 42/59 (71%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10.

OUTCOMES OF COMBINED PHACOEMULSIFICATION AND PARS PLANA VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT: A Comparative Study.

PURPOSE: To evaluate and to compare the anatomical and functional results of phacovitrectomy and pars plana vitrectomy (PPV) alone for phakic rhegmatogenous retinal detachment. METHODS: Retrospective, comparative case series of 266 phakic eyes that underwent either combined phacovitrectomy or PPV alone for primary retinal detachment. The primary anatomical success rate, the final best-corrected visual acuity, and the refractive outcomes were analyzed. RESULTS: One hundred and twenty-seven eyes were included in the combined group and 139 in the PPV group. The primary anatomical success rate was 84.3% in the combined group and 89.2% in the PPV group (P = 0.311). One hundred and nine (78.4%) eyes of the PPV group required cataract removal for visual rehabilitation during the follow-up period. There was no significant difference between the two groups in terms of the mean final best-corrected visual acuity (P = 0.185) and mean visual changes (P = 0.470). Overall, combined cataract extraction resulted in a significant myopic shift compared with delayed cataract surgery (P = 0.047). CONCLUSION: Combined phacoemulsification and PPV is a safe and effective procedure to treat retinal detachment. The anatomical and functional results were comparable with those obtained with PPV and delayed cataract surgery. However, the refractive outcomes were less favorable and shifted toward myopia, especially in macula-off cases.

Transient Retinal Dysfunctions after Acute Cannabis Use.

Although cannabis is very widespread worldwide, the impact of cannabis on visual function remains poorly understood. This is partly due to numerous difficulties met in developing clinical studies in cannabis users. Here, we report the first documented case of neuroretinal dysfunction after acute cannabis smoking. This observation was favored by the need of an annual ophthalmic evaluation in the context of a chloroquine intake for a systemic lupus erythematosus in a 47-year-old heavy cannabis user. A complete ophthalmic evaluation including visual acuity tests, intraocular pressure, fundoscopic examination, automated 10° central visual field, full-field electroretinogram (ERG) and multifocal ERG was performed twice - 30 min and 5 h after cannabis smoking. A strong decrease (up to 48%) in the a-wave amplitude of the full-field ERG was measured 30 min after cannabis smoking for all scotopic responses compared with the responses 5 h after smoking. Other tests showed reproducible results between the 2 series of measurements. This clinical case suggests that acute inhalation of cannabis affects the photoreceptors functioning. This rare situation suggests further investigations are required on the impact of cannabis on retinal processing, especially since cannabis has been incriminated in car injuries.

The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications.

Cannabis is one of the most prevalent drugs used in industrialized countries. The main effects of Cannabis are mediated by two major exogenous cannabinoids: ∆9-tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2. Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes. This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system. As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology. This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection. Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases. Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing.

Dissociated Optic Nerve Fiber Layer Appearance after Macular Hole Surgery: A Randomized Controlled Trial Comparing the Temporal Inverted Internal Limiting Membrane Flap Technique with Conventional Peeling.

PURPOSE: To evaluate the effect of the temporal inverted internal limiting membrane (ILM) flap technique compared with that of conventional ILM peeling on the extent of the dissociated optic nerve fiber layer (DONFL) and retinal sensitivity in patients undergoing macular hole (MH) surgery. DESIGN: Single-center, prospective, open-label, randomized controlled clinical trial. PARTICIPANTS: Patients requiring vitrectomy for MHs sized > 250 µm. METHODS: Patients were randomly assigned (1:1) to 1 of the following 2 groups: (1) the control group undergoing standard ILM peeling and (2) the experimental group (flap group) undergoing the temporal inverted ILM flap technique. MAIN OUTCOME MEASURES: The primary outcome measure was the total DONFL score at 3 months after surgery. Important secondary outcomes were microperimetry results, primary MH closure rate, external limiting membrane (ELM) and ellipsoid zone (EZ) recovery rates, and best-corrected visual acuity (BCVA). RESULTS: Sixty-five patients were recruited between February 2018 and July 2020; primary outcome data were available for 60 patients. The median DONFL score was 7.0 (3.0-12.5) in the control group and 5.0 (1.5-8.5) in the flap group at 3 months after surgery (P = 0.145). The focal depressions characteristic of the DONFL were limited to the temporal side of the fovea in the flap group, whereas they were found all around the fovea in the control group on spectral-domain OCT images. The MH closure rate (P = 1), EZ and ELM recovery rates (P = 0.252), and BCVA (P = 0.450) were similar between the 2 groups. The 3-month overall median retinal sensitivity (MRS) (P = 0.142) and MRS improvement (P = 0.916) in the control group were comparable with those observed in the flap group. In addition, there was no significant difference between the 2 techniques when considering the temporal area (P = 0.105) or the nasal area (P = 0.468). CONCLUSIONS: The temporal inverted ILM flap technique reduced the extent of the DONFL by preserving the nasal part of the fovea. However, the overall DONFL score was similar between the 2 techniques. In addition, the MRS and BCVA did not differ from those obtained after complete ILM peeling. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Efficacy of the DRL orthokeratology lens in slowing axial elongation in French children.

Background: This study aims to assess and compare the impact of Orthokeratology Double Reservoir Lens (DRL) versus Single Vision Lenses (SVL) on axial elongation and anterior chamber biometric parameters in myopic children over a 6- and 12-month treatment period in France. Methods: A retrospective study involving 48 patients aged 7 to 17 years, who underwent either orthokeratology treatment or single-vision spectacle correction, was conducted. Changes in refractive error, axial length, and anterior chamber depth were examined. Results: Twenty-five patients comprised the Orthokeratology (OK) group, while twenty-three were in the control group (single-vision spectacle group). Significant increases in mean axial length were observed over time in both the control (0.12 ± 0.13 mm and 0.20 ± 0.17 mm after 6 and 12 months, respectively; F (2,28.9) = 27.68, p < 0.001) and OK groups (0.02 ± 0.07 mm and 0.06 ± 0.13 mm after 6 and 12 months, respectively; F (2,29.1) = 5.30, p = 0.023). No statistically significant differences in axial length were found between male and female children (p > 0.620). Age-specific analysis revealed no significant axial elongation after 12 months in the 14-17 years group in the OK group. Anterior biometric data analysis at 6 and 12 months showed statistical significance only for the DRL group. Conclusion: Orthokeratology resulted in an 86 and 70% reduction in axial elongation after 6 and 12 months of lens wear, respectively, compared to the single-vision spectacles group. Myopia progression was more pronounced in younger children, underscoring the importance of initiating myopia control strategies at early ages.

Prevalence and predictive factors for posterior vitreous attachment in eyes undergoing epiretinal membrane surgery.

BACKGROUND: To report the prevalence of posterior vitreous attachment (PVA) in patients with idiopathic epiretinal membrane (iERM) and to determine associated preoperative predictive factors. METHODS: Retrospective observational case series of 408 eyes who underwent surgery for iERM without vitreomacular traction. The status of the posterior hyaloid was assessed intraoperatively. Predictive factors were analysed using univariate and multivariate logistic regression. We also evaluated the effect of PVA on the anatomical and functional outcomes of surgery. RESULTS: Eighty-two (20.1%) eyes were found to have an undetached posterior hyaloid during vitrectomy. In multivariate analysis, axial length (AL) and lens status were strongly associated with the posterior vitreous status (p = 0.031 and p = 0.048). The odds of having a PVA decreased by a factor 0.81 per mm of AL (95% CI, 0.66-1.00). Phakic eyes had a 2.88-fold increased risk of exhibiting PVA compared to those with previous cataract extraction (95% CI, 1.10-7.52). The presence of PVA did not have any effect on postoperative anatomical and functional outcomes. In contrast, we found that eyes with shorter axial length, low preoperative visual acuity and disruption of the ellipsoid zone exhibited worse visual recovery (p = 0.006, p < 0.001 and p = 0.037). CONCLUSION: PVA was observed in 20.1% of eyes undergoing vitrectomy for iERM. Shorter AL and phakic status were strong predictive factors of PVA in those eyes. However, the morphological features and the surgical prognosis of iERMs with PVA did not differ from those with posterior vitreous detachment.

Variations of retinal dysfunctions with the level of cannabis use in regular users: Toward a better understanding of cannabis use pathophysiology.

The impact of regular cannabis use on retinal function has already been studied using flash (fERG) and pattern (PERG) electroretinogram. Delayed ganglion and bipolar cells responses were observed as showed by increased peak time of PERG N95 and fERG b-wave recorded in photopic condition. Hypoactivity of amacrine cells was also showed by decreased amplitudes of oscillatory potentials (OPs). However, it is unknown how these retinal anomalies evolve according to the level of cannabis use in cannabis users. The aim of this study was to longitudinally assess the retinal function during a treatment aiming to reduce cannabis use. We recorded PERG and fERG in 40 regular cannabis users receiving either an 8 weeks mindfulness-based relapse prevention program or an 8 weeks treatment-as-usual therapy. ERGs were recorded before treatment, at the end of it, and 4 weeks afterward. We found reduced peak times in PERG N95 and fERG b-wave (p = 0.032 and p = 0.024: Dunn's post-hoc test) recorded at week 8 and increased amplitudes in OP2 and OP3 (p = 0.012 and p = 0.030: Dunn's post-hoc test) recorded at week 12 in users with decreased cannabis use. These results support variations of retinal anomalies with the level of cannabis use, implying that reduction of cannabis use could restore retinal function in regular users.

Retinal markers of therapeutic responses in major depressive disorder: Effects of antidepressants on retinal function.

BACKGROUND: One goal of research into major depressive disorder (MDD) is to develop markers to predict and monitor the response to psychotropic treatments. The retina is endowed with a complex neurotransmission system, composed of the main neurotransmitters involved in the pathophysiology of MDD. The retina is therefore a relevant site of investigation for the identification of reliable and robust markers. However, the effects of antidepressants on the human retina are poorly studied. Here, we seek to study the potential specific effects of various antidepressants on retinal function in MDD patients. METHODS: We assessed retinal function using flash (fERG), pattern (PERG) and multifocal (mfERG) electroretinogram in 19 MDD patients treated using antidepressants at baseline and at weeks 4, 8 and 12. RESULTS: We observed reduced b-wave amplitude of photopic fERG 3.0 in patients treated with Selective Serotonin Reuptake Inhibitor (SSRI) in comparison with patients treated with Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) or Tricyclic Antidepressant (TCAD). We also showed that SNRIs were associated both with a decrease in PERG P50 implicit time and an increase in fERG 3.0 b-wave amplitude. TCADs were associated with an increase in fERG flicker 3.0 a- and b-wave amplitude. CONCLUSIONS: This is the first study in real-life conditions to show a specific effect of various antidepressants on retinal function evaluated by electroretinogram. Further investigations should be led to specify the effects of antidepressants on ERG in order to isolate reliable and reproducible markers for predicting and monitoring the response to antidepressants.

Association of Microvasculature Changes with Visual Outcomes after Successful Retinal Detachment Surgery.

PURPOSE: To evaluate macular microvascular changes and their correlation with visual outcomes after rhegmatogenous retinal detachment (RRD) surgery. DESIGN: Retrospective case series. PARTICIPANTS: The study included 74 eyes successfully operated for RRD. METHODS: The foveal avascular zone area in the superficial capillary plexus, the vessel density (VD) in the superficial capillary plexus, vessel density deep capillary plexus (VD DCP), and choriocapillary plexus were evaluated using octangiography at 1 and 6 months postoperatively. The fellow eyes were used as controls for comparison. MAIN OUTCOME MEASURES: The correlation between octangiography parameters and postoperative best-corrected visual acuity (BCVA) was assessed using a hybrid linear mixed model. We also analyzed the relationship between octangiography parameters and the integrity of the external limiting membrane (ELM) and ellipsoid zone (EZ) of photoreceptors. RESULTS: The median VD DCP was significantly decreased in RRD eyes at 1 month (P = 0.019), but gradually improved over time to reach the value of the fellow eyes at 6 months (P = 1). There was no significant difference between the 2 groups in median foveal avascular zone area, superficial capillary plexus, and choriocapillary plexus (P = 0.579, P = 0.618, P = 0.068 and P = 0.819, P = 1, and P = 1, respectively) at both 1 and 6 months postoperatively. Postoperative BCVA was positively correlated with VD DCP (P = 0.009) in multivariate analysis. Eyes with low 1-month VD DCP tended to have worse final BCVA (P = 0.067). There was no correlation between VD DCP and ELM and/or EZ integrity at both 1 (P = 0.156) and 6 months postoperatively (P = 0.161). Eyes with intact ELM and EZ at 6 months, however, had significantly higher 1-month VD DCP than those with disrupted ELM and/or EZ (P = 0.027). CONCLUSION: The VD DCP was affected in RRD eyes as well as strongly associated with postoperative BCVA and the restoration of photoreceptor layers. It might thus serve as a predictor for visual recovery following successful RRD surgery.

Retinal electroretinogram features can detect depression state and treatment response in adults: A machine learning approach.

BACKGROUND: Major depressive disorder (MDD) is a major public health problem. The retina is a relevant site to indirectly study brain functioning. Alterations in retinal processing were demonstrated in MDD with the pattern electroretinogram (PERG). Here, the relevance of signal processing and machine learning tools applied on PERG was studied. METHODS: PERG - whose stimulation is reversible checkerboards - was performed according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standards in 24 MDD patients and 29 controls at the inclusion. PERG was recorded every 4 weeks for 3 months in patients. Amplitude and implicit time of P50 and N95 were evaluated. Then, time/frequency features were extracted from the PERG time series based on wavelet analysis. A statistical model has been learned in this feature space and a metric aiming at quantifying the state of the MDD patient has been derived, based on minimum covariance determinant (MCD) mahalanobis distance. RESULTS: MDD patients showed significant increase in P50 and N95 implicit time (p = 0,006 and p = 0,0004, respectively, Mann-Whitney U test) at the inclusion. The proposed metric extracted from the raw PERG provided discrimination between patients and controls at the inclusion (p = 0,0001). At the end of the follow-up at week 12, the difference between the metrics extracted on controls and patients was not significant (p = 0,07), reflecting the efficacy of the treatment. CONCLUSIONS: Signal processing and machine learning tools applied on PERG could help clinical decision in the diagnosis and the follow-up of MDD in measuring treatment response.

Altered central vision and amacrine cells dysfunction as marker of hypodopaminergic activity in treated patients with schizophrenia.

BACKGROUND: Retinal dysfunction is widely documented in schizophrenia using flash (fERG) and pattern electroretinograms (PERG), but the role of dopamine transmission has seldom been explored. METHODS: We explored the role of dopamine transmission by evaluating the spatial location of retinal anomalies using multifocal ERG (mfERG) in photopic condition and the oscillatory potentials (OPs) extracted from fERG measured in scotopic condition in 29 patients with schizophrenia and 29 healthy controls. RESULTS: With the mfERG, our main results revealed reduced amplitudes in the center of the retina: P1 (p < .005) and N2 amplitudes (p < .01) in the <2° region, N1 (p < .0005) and P1 amplitudes (p < .001) in the 2-5° region and P1 amplitude (p < .05) in the 5-10° region. For OPs, our results showed a decrease in the O1 (p < .005), O2 (p < .005), O3 (p < .05) and overall O1, O2, O3 index amplitudes (p < .005) in patients with schizophrenia. CONCLUSIONS: Both the central location of retinal dysfunctions of the mfERG and OPs results could reflect a hypodopaminergic effect in patients with schizophrenia. In future studies, OPs should be considered as a measure to evaluate the hypodopaminergy in patients.

Bipolar disorders and retinal electrophysiological markers (BiMAR): Study protocol for a comparison of electroretinogram measurements between subjects with bipolar disorder and a healthy control group.

Background: Bipolar disorders (BD) is a common, chronic and disabling psychiatric condition. In addition to being characterized by significant clinical heterogeneity, notable disturbances of sleep and cognitive function are frequently observed in all phases of the disease. Currently, there is no readily available biomarker in current clinical practice to help diagnose or predict the disease course. Thus, identification of biomarkers in BD is today a major challenge. In this context, the study of electrophysiological biomarkers based on electroretinogram (ERG) measurements in BD seems highly promising. The BiMAR study aims to compare electrophysiological data measured with ERG between a group of euthymic patients with BD and a group of healthy control subjects. Secondarily, we will also describe the existing potential relationship between clinical, sleep and neuropsychological phenotypes of patients and electrophysiological data. Methods: The BiMAR study is a comparative and monocentric study carried out at the Expert Center for BD in Nancy, France. In total, 70 euthymic adult patients with BD and 70 healthy control subjects will be recruited. Electrophysiological recordings with ERG and electroencephalogram (EEG) will be performed with a virtual reality headset after a standardized clinical evaluation to all participants. Then, an actigraphic monitoring of 21 consecutive days will be carried out. At the end of this period a neuropsychological evaluation will be performed during a second visit. The primary outcome will be electrophysiological measurements with ERG flash and pattern. Secondary outcomes will be EEG data, sleep settings, clinical and neuropsychological assessments. For patients only, a complementary ancillary study, carried out at the University Hospital of Nancy, will be proposed to assess the retinal structure and microvascularization using Optical Coherence Tomography. Recruitment started in January 2022 and will continue until the end of July 2023. Discussion: The BiMAR study will contribute to identifying candidate ERG electrophysiological markers for helping the diagnosis of BD and identify subgroups of patients with different clinical profiles. Eventually, this would allow earlier diagnosis and personalized therapeutic interventions. Clinical trial registration: The study is registered at Clinicaltrials.gov, NCT05161546, on 17 December 2021 (https://clinicaltrials.gov/ct2/show/NCT05161546).

Visual electrophysiology and neuropsychology in bipolar disorders: A review on current state and perspectives.

Bipolar disorder is a lifelong condition. Today, there is a urgent need to find indicators of the disease. Specifically, they could be useful to improve the diagnosis and the early detection, the prognosis, to estimate the treatment response and to create homogeneous subgroups of patients based on similar pathophysiological mechanisms. Here, we assume that visual electrophysiology in combination with a neuropsychological assessment can give additional data to routine practice, especially to precise specific damages and pathophysiological characteristics of these patients. Visual electrophysiology is characterized by an electroretinogram and the delivery of visual evoked potentials, which measure retinal and visual cortical neuronal functioning in response to visual stimulations. This review highlights the interest of visual electrophysiology and neuropsychology performed in isolation and to present the benefits of combining these measures. We will review the results based on these measures in patients with bipolar disorders. Finally, we argue for the use of innovative techniques such as signal processing and artificial intelligence techniques for routine care and precision medicine in bipolar disorders.

Retinal structural changes in mood disorders: The optical coherence tomography to better understand physiopathology?

BACKGROUND: Mood disorders are particularly common, disabling conditions. Diagnosis can be difficult as it may involve different pathophysiological assumptions. This could explain why such disorders are resistant to treatment. The retina is part of the central nervous system and shares a common embryonic origin with the brain. Optical coherence tomography (OCT) is an imaging technique for analysing the different layers of the retina. We reviewed studies that examined the retina with OCT in mood disorders. METHODS: We conducted Pubmed search and additional manual research based on the bibliography in each of selected articles. We found and analysed 11 articles relevant to our subject. RESULTS: This literature review confirms that it is possible to use OCT to detect neurodegeneration and neuroinflammation in mood disorders. Their impact is thought to depend on the duration and severity of the disease, and whether it is in acute or chronic stage. The differences seen in studies dealing with depression and those looking at bipolar disorder may reflect the particular characteristics of each disorder. A number of OCT parameters can be proposed as biomarkers of active or chronic inflammation and neurodegeneration. Markers of predisposition to an at-risk mental state are also suggested. LIMITATIONS: The main limitation is selection bias, studies including more varied population would help to confirm and precise these results. CONCLUSION: OCT is thus a particularly promising tool for evaluating some of the etiopathogenetic mechanisms involved in mood disorders. The combination with other approaches could help to find more specific biomarkers.

Oscillatory potentials abnormalities in regular cannabis users: Amacrine cells dysfunction as a marker of central dopaminergic modulation.

BACKGROUND: Cannabis is a neuromodulating substance that acts on central synaptic transmission. Regular cannabis use induces a decreased capacity for dopamine synthesis in the brain. The retina is considered an easy means of investigating dysfunctions of synaptic transmission in the brain. We have previously studied the impact of regular cannabis use on retinal function. Using the N95 wave of the pattern electroretinogram, we found a 6 ms-delayed ganglion cells response. Using the b-wave of the photopic flash electroretinogram, we found a 1 ms-delayed bipolar cells response. Here, we investigated amacrine cells function because these cells are located between the bipolar cells and the ganglion cells and contribute to amplifying the signal between these two layers of the retina. We tested the effect of regular cannabis use on these retinal dopaminergic cells. We assessed the role of these cells in amplifying the delay observed previously. METHODS: We recorded dark-adapted 3.0 flash ERG oscillatory potentials in 56 regular cannabis users and 29 healthy controls. The amplitude and implicit time of OP1, OP2, OP3 and OP4 were evaluated. RESULTS: Cannabis users showed a significant decrease in OP2 amplitude (p = 0.029, Mann-Whitney test) and OP3 amplitude (p = 0.024, Mann-Whitney test). No significant difference was found between the groups for OP1 and OP4 amplitude or for the implicit time of oscillatory potentials. CONCLUSIONS: These results reflect the impact of regular cannabis use on amacrine cells function. They highlight abnormalities in dopaminergic transmission and are similar to those found in Parkinson's disease. Oscillatory potentials could be used as markers of central dopaminergic modulation.

Retinal dysfunctions in regular tobacco users: The retina as a window to the reward circuit in addictive disorders.

The nicotine contained in tobacco is a neuromodulator which affects neurotransmission within the brain. The retina is an easy way to study central synaptic transmission dysfunctions in neuropsychiatric disorders. The purpose of this study is to assess the impact of regular tobacco use on retinal function using pattern (PERG), flash (fERG) and multifocal (mfERG) electroretinogram (ERG). We recorded PERG, fERG and mfERG for 24 regular tobacco users and 30 healthy non-smoking subjects. The protocol was compliant with International Society for Clinical Electrophysiology of Vision standards. The amplitudes and peak times (PT) of P50, N95 waves (PERG), a-, b- and oscillatory potentials (fERG), and N1, P1, N2 (mfERG) were evaluated. Compared to non-smokers, the results (Mann-Whitney U test, Bonferroni correction) for tobacco users suggested a significant increase of ~ 1 ms in the PT of light-adapted 3.0 fERG b-wave (p = 0.002). Using mfERG, we observed the following increases in tobacco users: in ring 3 for P1 PT of ~1,5 ms and in ring 5 for P1 PT of ~ 1 ms and for N2 PT of ~ 1 ms (p = 0.002, p = 0.002 and p = 0.006). It is our hypothesis that these results reflect the consequences of regular tobacco use on retinal synaptic transmission, and more specifically on dopaminergic and cholinergic transmission. We deduce that the retina may provide a crucial site of investigation for neurotransmission modulation of the reward circuit in regular tobacco users.