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In 2021, Ocular Therapeutix expanded the indications for dexamethasone ophthalmic insert 0.4 mg (Dextenza) upon its FDA approval to treat ocular itching associated with allergic conjunctivitis (AC). It is the [...]

Introduction: Abnormal findings on optical coherence tomography (OCT) and electroretinography (ERG) have been reported in participants with schizophrenia spectrum disorders (SSDs). This study aims to reveal the pooled standard mean difference (SMD) in retinal parameters on OCT and ERG among participants with SSDs and healthy controls and their association with demographic characteristics, clinical symptoms, smoking, diabetes mellitus, and hypertension. Methods: Using PubMed, Scopus, Web of Science, and PSYNDEX, we searched the literature from inception to March 31, 2023, using specific search terms. This study was registered with PROSPERO (CRD4202235795) and conducted according to PRISMA 2020. Results: We included 65 studies in the systematic review and 44 in the meta-analysis. Participants with SSDs showed thinning of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer- inner plexiform cell layer, and retinal thickness in all other segments of the macula. A meta-analysis of studies that excluded SSD participants with diabetes and hypertension showed no change in results, except for pRNFL inferior and nasal thickness. Furthermore, a significant difference was found in the pooled SMD of pRNFL temporal thickness between the left and right eyes. Meta-regression analysis revealed an association between retinal thinning and duration of illness, positive and negative symptoms. In OCT angiography, no differences were found in the foveal avascular zone and superficial layer foveal vessel density between SSD participants and controls. In flash ERG, the meta-analysis showed reduced amplitude of both a- and b-waves under photopic and scotopic conditions in SSD participants. Furthermore, the latency of photopic a-wave was significantly shorter in SSD participants in comparison with HCs. Discussion: Considering the prior report of retinal thinning in unaffected first-degree relatives and the results of the meta-analysis, the findings suggest that retinal changes in SSDs have both trait and state aspects. Future longitudinal multimodal retinal imaging studies are needed to clarify the pathophysiological mechanisms of these changes and to clarify their utility in individual patient monitoring efforts.

LIGHT INDUCED visual (LIV) -response (the use of light to stimulate electrical responses from cells within the eye) has recently emerged as a better way to describe visual electrophysiology testing. [...]

A subset of individuals with schizophrenia (SZ) are thought to have a microvascular component to their illness with studies demonstrating alterations in retinal superficial, deep, and choroidal microvasculature networks. However, the direction and location of these alterations have differed across studies. In a recent study, we reported that individuals with SZ demonstrated lower superficial layer perfusion density than a healthy control (HC) group. The current study investigated characteristics of the deep vascular layer in SZ. We included 28 individuals with a diagnosis of SZ or schizoaffective disorder, and 37 HCs. Optical coherence tomography angiography (OCTA) data was collected to measure deep retinal layer perfusion density, skeletonized vessel density, vessel diameter index, and fractal dimension. We conducted between-group comparisons to examine differences in these OCTA variables between SZ and HC groups. A trend analysis was conducted to determine if differences reflected a linear trend according to age and illness length, and Spearman correlations were conducted to determine associations between deep and superficial layer density. Individuals with SZ demonstrated significantly lower bilateral perfusion density and vessel diameter index, as well as lower left eye skeletonized vessel density and fractal dimension. There was a significant linear trend in the data indicating that individuals with chronic SZ demonstrated the lowest OCTA values, followed by individuals within two years of their first episode of psychosis who did not differ from older controls, followed by younger controls, who demonstrated the highest values in at least one eye. Lower density values in the deep retinal layer were also significantly associated with lower density values in the superficial layer. Overall, results suggest that microvascular alterations are present in multiple retinal layers in SZ and that they may be useful visual system biomarkers of neurovascular changes in the disorder.

Subconcussive head hits (SHH) are common in contact sport athletes and are predictive of the later development of cognitive and brain changes, including chronic traumatic encephalopathy. In this pilot study we determined whether a history of concussion, and SHH acquired during a single season of college football, were associated with changes on retinal biomarkers of central nervous system (CNS) structure and function. College football players with a history of concussion (FB+C; n=9) or without a concussion history (FB-C; n=11), and non-contact sport collegiate athletes (Track/Swim; n=12) underwent visual and cognitive testing, retinal imaging (optical coherence tomography (OCT) and OCT angiography (OCTA)), and electroretinography (ERG) at three time points: pre-season, post-season and 4-month follow-up. The FB+C group demonstrated thicker maculae and exaggerated ERG waveforms (from all retinal neural cell types) compared to the other groups. These changes were generally observed at all timepoints, suggesting long-term changes associated with concussions, rather than effects of recent football activity. However, we also observed significant relationships between the number of head impacts during the season and stronger ERG responses, degree of macula thickening, enlargement of optic disc parameters, and increases in the density of retinal microvasculature relative to controls. These data suggest that retinal biomarkers are sensitive to both long- and short-term CNS changes related to participation in football, even in young athletes.

People with psychosis and mood disorders experience disruptions in working memory; however, the underlying mechanism remains unknown. We focused on 2 potential mechanisms: first, poor attentional engagement should be associated with elevated levels of prestimulus alpha-band activity within the electroencephalogram (EEG), whereas impaired working memory encoding should be associated with reduced poststimulus alpha suppression.

Parkinson’s disease (PD) is known to affect retinal structure and activity. As such, retinal evaluations may be used to develop objective and possibly early PD diagnostic tools. The aim of this study was to investigate the effects of Parkinson’s disease (PD) manifestation and treatment on retinal activity. Data were collected on 21 participants diagnosed with PD, including the number of medications taken, clinical scales and flash electroretinography (fERG) measurements, under light-adapted and dark-adapted conditions. The fERG parameters measured included a-wave and b-wave amplitude and implicit time (i.e., latency). First, we investigated correlations between symptom measure scores and the fERG parameters. Next, we divided participants into two groups based on their antiparkinsonian medication load and analyzed differences between these groups’ fERG parameters. fERG parameters were strongly correlated with a number of clinical variables, including motor and non-motor symptoms and age at PD onset. Photoreceptor cell implicit time was longer among participants taking one or less antiparkinsonian medication as compared to those taking two or more. However, overall there was not strong evidence of a relationship between the number of antiparkinsonian medications taken and the fERG parameters. Findings suggest that fERG may be a useful, non-intrusive measure of retinal, and, perhaps overall CNS function, in PD. However, additional studies in larger samples are needed to clarify this association.

Published findings on the relationship between schizophrenia and violence have been mixed, due to differences in study design and quality. In this review, we address the issue with an emphasis on characterizing who is most likely to be violent and when. We conclude that: (1) individuals with schizophrenia are at an increased risk for violence due to specific psychotic symptoms; (2) this risk is increased by brain abnormalities, psychiatric comorbidities, and demographic factors that are not specific to schizophrenia; (3) the majority of violent offenses committed by people with schizophrenia are indistinguishable from offenses committed by others; and (4) despite our knowledge of factors related to increased violence risk and the existence of effective treatments to mitigate this risk, valid risk assessment instruments for this population are lacking, and treatment strategies are rarely employed at any level of psychiatric care. In short, while most people with schizophrenia are not violent and violence committed by people with this condition accounts for only a small percentage of overall violent crime, there is nevertheless a significantly increased risk for violence among subgroups in this population. This has implications for people living with people with schizophrenia, mental health professionals, administrators of psychiatric care facilities, law enforcement personnel, the court system, and policymakers.

The predictive coding theory of psychosis posits that individuals with schizophrenia demonstrate abnormalities in the strength of top-down modulation (based on prior experience) of sensory signals. Evidence suggests that difficulty perceiving depth inversion illusions (DIIs) (i.e., more accurate perception of stimuli under conditions in which control subjects perceive these illusions) may reflect this abnormality in people with schizophrenia. This review synthesizes findings from all studies that have investigated DII perception in schizophrenia, high-risk syndromes, and conditions associated with risk for psychosis outside of a psychotic disorder such as those involving cannabis use, alcohol intoxication and withdrawal, and sleep deprivation. Cognitive and biological mechanisms contributing to DII resistance, and strengths and confounds of using the DII task as a measure of predictive coding are also discussed. The available evidence indicates that psychosis is associated with resistance to DIIs, whereas schizophrenia in the absence of active psychosis is less strongly associated with this effect. This may be due to psychosis-related deficiencies in top-down signaling and a compensatory overreliance on bottom-up signaling. Overall, the evidence reviewed suggests that the DII task is a sensitive measure of predictive coding in schizophrenia that could be used as a visual biomarker to predict risk and impending changes in clinical state within the disorder. Additional studies that measure changes longitudinally are necessary to further explore the possibility of using the DII task as a visual biomarker for psychosis in clinical settings.

AbstractPerceptual organization (PO) impairments have been repeatedly demonstrated in schizophrenia. The extent to which these impairments can be reduced or eliminated, however, has received less attention, and evidence on this issue has not been previously reviewed. The literature suggests that whether normal experience-dependent change in perceptual organization occurs in schizophrenia depends on factors such as: stimulus grouping strength, extent of practice, type of cues upon which top-down feedback can be generated, and patient characteristics (trait and state). Therefore, the purpose of this paper is to review and synthesize the available evidence on plasticity and other forms of change in PO in schizophrenia, and to relate it to current data and theories on plasticity, including perceptual learning (PL) in healthy people. This can clarify the computational and neural mechanisms involved in experience-dependent and state-related aspects of PO in schizophrenia, and also contribute to a greater understanding of the mechanisms involved in normal PL. A major finding that emerges from a review of the data is that the conditions under which PL of PO does notoccur in schizophrenia closely parallel the conditions under which PO is reduced in a single test administration. That is, when stimulus-driven cues to grouping are strong, PL of PO occurs in patients; in contrast, when top-down feedback is required to organize novel or weakly grouped stimuli, PL of PO tends notto occur in patients. Moreover, even with strongly grouping stimuli, change tends to occur only via repetition; when processing of more abstract cues is required to generate top-down feedback, change tends not to occur. In addition, within-session PL in people with schizophrenia appears to be more impaired than learning over multiple days, supporting the separability of fast and slow plasticity mechanisms; however, more research with a larger class of stimuli is needed on this issue.

ABSTRACTObjective:To compare the intraocular pressurelowering efficacy and safety of topical bimatoprost 0.03% with that of travoprost 0.004% for the reatment of black patients with open-angle glaucoma (OAG) and ocular hypertension (OHT).Research design and methods:Multicenter, prospective, randomized, investigator-masked trial of 94 black patients previously diagnosed with OAG or OHT. All patients completed washout of ocular hypotensive medications before study participation. Patients were assigned to either once-daily bimatoprost 0.03% or once-daily travoprost 0.004% for 3 months.Main outcome measures:The primary outcome measures were mean intraocular pressure (IOP), mean change from baseline IOP, and percentage of patients who reached a target IOP reduction. Secondary measures included ophthalmologic examination and adverse events.Results:Both bimatoprost and travoprost significantly lowered IOP at all study visits ( p< 0.001). Bimatoprost provided mean IOP reductions from baseline that ranged from 6.8 mmHg to 7.8 mmHg (27% to 31%). Travoprost provided mean IOP reductions from baseline that ranged from 6.2 mmHg to 6.9 mmHg (25% to 28%). By month 3, 85% of participants in the bimatoprost group had a mean IOP reduction of at least 20%, compared with 68% of those in the travoprost group. Furthermore, 31.9% of those in the bimatoprost group had a mean IOP reduction of more than 40% at month 3 compared with 20.9% of those in the travoprost group. There were no significant differences in biomicroscopy, ophthalmoscopy, or visual acuity. Ocular redness was the most commonly reported adverse event in both treatment groups. No serious adverse events were reported.Conclusions:Bimatoprost and travoprost each effectively lowered IOP in this population of black patients. More patients achieved clinically relevant IOP reductions with bimatoprost.

Psychiatric rehabilitation refers to a treatment philosophy and to a set of assessment and treatment techniques designed to reduce disability and maximize environmental adaptation. The field of psychiatric rehabilitation of schizophrenia is now well developed, and successful interventions exist for teaching many essential community-living skills and for promoting maintenance and generalization of these gains. Recent developments include the creation of new skills-training interventions and cognitive rehabilitation techniques and improvements in the delivery of vocational and substance abuse treatments. As a field, psychiatric rehabilitation is continuing to develop in a manner that is responsive to perceived treatment needs, shortcomings of existing interventions, and developments in related fields (e.g., social psychology, neuroscience of schizophrenia). Some of these developments in theory and research point to areas of conceptual/theoretical weaknesses in existing treatments and assessment measures and suggest directions for further development. This article reviews the current status of a number of areas within the psychiatric rehabilitation of schizophrenia, highlighting future needs.

Psychiatric diagnosis and treatment have historically taken a symptom-based approach, with less attention on identifying underlying symptom-producing mechanisms. Recent efforts have illuminated the extent to which different underlying circuitry can produce phenotypically similar symptomatology (e.g. psychosis in bipolar disorder vs schizophrenia). Computational modelling makes it possible to identify and mathematically differentiate behaviorally-unobservable, specific reinforcement-learning (RL) differences in schizophrenia (SZ) patients versus other disorders, likely due to a higher reliance on prediction-error(PE)-driven learning associated with basal ganglia, and under-reliance on explicit value representations associated with OFC.

Recent studies have found evidence of retinal thinning in schizophrenia spectrum disorder patients; however, it is not known whether retinal thinning is present at the first episode of psychosis or whether it is a result of the progression of the disease or related factors (e.g., emergence of medical comorbidities). We hypothesized that first episode patients (FEP) would not differ on any retinal variables when compared to age matched controls, while chronically ill patients would show evidence of retinal thinning compared to age matched controls.

•Severe mental illnesses and many neurodegenerative disorders are characterized by thinning of retinal structures as indicated by optical coherence tomography (OCT) and by retinal dysfunction as indicated by electroretinography (ERG).•In many cases, studies indicate significant correlations between retinal changes and clinical and neuropathological features such as cognitive decline, brain volume loss, overall illness severity, and progression of illness.•Retinal indices have the potential to serve as biomarkers of disease onset and progression, relapse, course, and treatment response.•Recent advances in imaging of retinal activity in vivo, and in data analysis techniques, have the potential to significantly improve the predictive validity of retinal measures.