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Vision, more than any other sense, dominates our mental life. Our conscious visual experience of the world is so rich and detailed that we can hardly distinguish it from the real thing. But as Goodale and Milner make clear in their prize-winning book, Sight Unseen, our visual experience of the world is not all there is to vision. Some of the most important things that vision does for us never reach our consciousness at all. In this updated and extended new edition, Goodale and Milner explore one of the most extraordinary neurological cases of recent years--one that profoundly changed scientific views on the visual brain. It is the story of Dee Fletcher--a young woman who became blind to shape and form as a result of brain damage. Dee was left unable to recognize objects or even tell one simple geometric shape from another. As events unfolded, however, Goodale and Milner found that Dee wasn't in fact blind -- she just didn't know that she could see. They showed, for example, that Dee could reach out and grasp objects with amazing dexterity, despite being unable to perceive their shape, size, or orientation. Taking us on a journey into the unconscious brain, the two scientists who made this incredible discovery tell the amazing story of their work, and the surprising conclusion they were forced to reach. Written to be accessible to students and popular science readers, this book is a fascinating illustration of the power of the 'unconscious' mind.

To describe CONCUSS, a randomized clinical trial (RCT) designed to compare the following: the effectiveness of immediate office-based vergence/accommodative therapy with movement (OBVAM) to delayed OBVAM as treatments for concussion-related convergence insufficiency (CONC-CI) to understand the impact of time (watchful waiting), the effect of OBVAM dosage (12 versus 16 therapy sessions), and to investigate the underlying neuro-mechanisms of OBVAM on CONC-CI participants. CONCUSS is an RCT indexed on https://clinicaltrials.gov/study/NCT05262361 enrolling 100 participants aged 11-25 years with medically diagnosed concussion, persistent post-concussive symptoms 4-24 weeks post-injury, and symptomatic convergence insufficiency. Participants will receive standard concussion care and will be randomized to either immediate OBVAM or delayed (by six weeks) OBVAM. At the Outcome 1 examination (week 7), clinical assessments of success as determined by changes in the near point of convergence (NPC), positive fusional vergence (PFV), and symptoms will be compared between the two treatment groups. After the Outcome 1 visit, those in the delayed group receive 16 visits of OBVAM, while those in the immediate OBVAM group receive four more therapy visits. Outcome 2 assessment will be used to compare both groups after participants receive 16 sessions of OBVAM. The primary measure is the between-group differences of the composite change in the NPC and PFV at the Outcome 1 visit. Secondary outcome measures include individual clinical measures, objective eye-tracking parameters, and functional brain imaging. Major features of the study design include formal definitions of conditions and outcomes, standardized diagnostic and treatment protocols, a delayed treatment arm, masked outcome examinations, and the incorporation of objective eye movement recording and brain imaging as outcome measures. CONCUSS will establish best practices in the clinical care of CONC-CI. The objective eye movement and brain imaging, correlated with the clinical signs and symptoms, will determine the neuro-mechanisms of OBVAM on CONC-CI.

Introduction Convergence Insufficiency (CI) is the most prevalent oculomotor dysfunction of binocular vision that negatively impacts quality of life when performing visual near tasks. Decreased resting‐state functional connectivity (RSFC) is reported in the CI participants compared to binocularly normal control participants. Studies report that therapeutic interventions such as office‐based vergence and accommodative therapy (OBVAT) can improve CI participants' clinical signs, visual symptoms, and task‐related functional activity. However, longitudinal studies investigating the RSFC changes after such treatments in participants with CI have not been conducted. This study aimed to investigate the neural basis of OBVAT using RSFC in CI participants compared to the placebo treatment to understand how OBVAT improves visual function and symptoms. Methods A total of 51 CI participants between 18 and 35 years of age were included in the study and randomly allocated to receive either 12 one‐hour sessions of OBVAT or placebo treatment for 6 to 8 weeks (1 to 2 sessions per week). Resting‐state functional magnetic resonance imaging and clinical assessments were evaluated at baseline and outcome for each treatment group. Region of interest (ROI) analysis was conducted in nine ROIs of the oculomotor vergence network, including the following: cerebellar vermis (CV), frontal eye fields (FEF), supplementary eye fields (SEF), parietal eye fields (PEF), and primary visual cortices (V1). Paired t‐tests assessed RSFC changes in each group. A linear regression analysis was conducted for significant ROI pairs in the group‐level analysis for correlations with clinical measures. Results Paired t‐test results showed increased RSFC in 10 ROI pairs after the OBVAT but not placebo treatment (p < 0.05, false discovery rate corrected). These ROI pairs included the following: Left (L)‐SEF–Right (R)‐V1, L‐SEF–CV, R‐SEF–R‐PEF, R‐SEF–L‐V1, R‐SEF–R‐V1, R‐SEF–CV, R‐PEF–CV, L‐V1–CV, R‐V1–CV, and L‐V1–R‐V1. Significant correlations were observed between the RSFC strength of the R‐SEF–R‐PEF ROI pair and the following clinical visual function parameters: positive fusional vergence and near point of convergence (p < 0.05). Conclusion OBVAT, but not placebo treatment, increased the RSFC in the ROIs of the oculomotor vergence network, which was correlated with the improvements in the clinical measures of the CI participants. Office‐based Vergence and Accommodative Therapy, but not placebo therapy, improves the resting‐state functional connectivity in the regions of the oculomotor vergence network which is correlated with the improvements in the clinical measures using in the assessment and diagnosis of CI.

Endosomes have emerged as a central hub and pathogenic driver of Alzheimer’s disease (AD). The earliest brain cytopathology in neurodegeneration, occurring decades before amyloid plaques and cognitive decline, is an expansion in the size and number of endosomal compartments. The strongest genetic risk factor for sporadic AD is the ε4 allele of Apolipoprotein E (ApoE4). Previous studies have shown that ApoE4 potentiates presymptomatic endosomal dysfunction and defective endocytic clearance of amyloid beta (Aβ), although how these two pathways are linked at a cellular and mechanistic level has been unclear. Here, we show that aberrant endosomal acidification in ApoE4 astrocytes traps the low-density lipoprotein receptor-related protein (LRP1) within intracellular compartments, leading to loss of surface expression and Aβ clearance. Pathological endosome acidification is caused by ε4 risk allele-selective down-regulation of the Na⁺/H⁺ exchanger isoform NHE6, which functions as a critical leak pathway for endosomal protons. In vivo, the NHE6 knockout (NHE6KO) mouse model showed elevated Aβ in the brain, consistent with a causal effect. Increased nuclear translocation of histone deacetylase 4 (HDAC4) in ApoE4 astrocytes, compared with the nonpathogenic ApoE3 allele, suggested a mechanistic basis for transcriptional down-regulation of NHE6. HDAC inhibitors that restored NHE6 expression normalized ApoE4-specific defects in endosomal pH, LRP1 trafficking, and amyloid clearance. Thus, NHE6 is a downstream effector of ApoE4 and emerges as a promising therapeutic target in AD. These observations have prognostic implications for patients who have Christianson syndrome with loss of function mutations in NHE6 and exhibit prominent glial pathology and progressive hallmarks of neurodegeneration.

Accommodative dysfunction is a common oculomotor sequelae of mild traumatic brain injury (mTBI). This study evaluated a range of dynamic (objective) and static (subjective) measures of accommodation in 12 nonstrabismic individuals with mTBI and near vision-related symptoms before and after oculomotor training (OMT) and placebo (P) training (6 wk, two sessions per week, 3 h of training each). Following OMT, the dynamics of accommodation improved markedly. Clinically, there was a significant increase in the maximum accommodative amplitude both monocularly and binocularly. In addition, the near vision symptoms reduced along with improved visual attention. None of the measures were found to change significantly following P training. These results provide evidence for a significant positive effect of the accommodatively based OMT on accommodative responsivity. Such improvement is suggestive of oculomotor learning, demonstrating considerable residual brain-visual system plasticity in the adult compromised brain.

PurposeTo determine the outcomes of three different techniques of strabismus surgery in patients with convergence insufficiency intermittent exotropia (CI-X(T)).Patients and methodsSixty-seven patients with CI-X(T) with near-distance disparity (NDD) ≥10 prism diopter (PD) were included in this 1-year follow-up prospective study and were randomly divided into three groups: slanted bilateral LR recession (S-BLR) group in which 22 patients underwent bilateral slanting recession of the lateral rectus (LR) muscle, the I-RR group with 23 patients who underwent improved unilateral medial rectus (MR) resection and LR recession with the amounts of resection and recession biased to near and distance deviation, respectively, and the A-BLR group with 22 patients who underwent bilateral augmented LR recession based on the near deviation. A successful outcome at distant and near was defined as exodeviation between 10 PD of exophoria/tropia and 5 PD of esophoria/tropia. Cumulative probabilities of success, preoperative and postoperative distant, near deviations, and NDD among groups were analyzed and compared.ResultsThe success rate of distant exodeviation, near exodeviation, and NDD in the three groups after 1 year was statistically insignificant (P=0.054, 0.233, and 0.142, respectively). At the 1 year follow-up, vertical pattern strabismus (V and A patterns) was a feature of the S-BLR group, whereas the rate of postoperative overcorrection and undercorrection was significant in the A-BLR and I-RR groups, respectively.ConclusionThe success rate of correction of distant exodeviation, near exodeviation, and NDD was statistically indifferent among the three groups. However, each procedure has its specific postoperative concerns, which should be considered before implementing in patients with CI-X(T).

Purpose To compare the efficacy and safety of combination therapy with orbital irradiation and systemic steroids versus steroid monotherapy in the management of active Graves’ orbitopathy (GO). Methods The clinical charts of 127 patients with active inflammation due to GO who received intravenous steroid pulse therapy as a first-line treatment with or without orbital radiotherapy between 2010 and 2014 were reviewed. Patients were divided into two treatment groups: 1) combined orbital radiotherapy and steroid pulse therapy (SRT group) and 2) steroid pulse therapy only (ST group). Primary outcome measures included clinical activity score (CAS); NOSPECS classification; ocular motility impairment; and exophthalmos at 1, 3, 6, and 12 months after treatment. The secondary outcome measure was the change in orbital, extraocular muscle (EOM), and fat volume after treatment measured by orbit computed tomography. Results Sixty-eight patients were included in the SRT group, and 59 patients were in the ST group. In both treatments, CAS and NOSPECS were significantly reduced. In the comparison of the degree of change from baseline between the groups, the SRT group demonstrated more improvement in NOSPECS and scores of ocular motility. Orbital, EOM, and fat volume significantly decreased in the SRT group; however, only fat volume was reduced in the ST group. Compressive optic neuropathy after treatment developed in 0 % of the SRT group and 3.4 % (2/59) of the ST group. Reactivation of inflammation occurred in 11.8 % (8/68) of the SRT group and 28.8 % (17/59) of the ST group. Conclusions Orbital radiotherapy in combination with steroid treatment significantly improved ocular motility by reducing EOM volume in patients with active GO.

Background Eye movement dysfunction has been widely observed in several neurodegenerative diseases. Normal pressure hydrocephalus (NPH) is a treatable condition showing marked clinical and radiological overlap with neurodegenerative parkinsonism and dementia syndromes, often posing diagnostic challenges. The current study employed video-oculography (VOG) aiming to comprehensively explore possible ocular dysfunction in NPH patients. Methods Forty-two consecutive NPH patients and seventy-six healthy controls (HC) were enrolled in the study. Participants underwent a video-oculographic assessment including reflexive saccades and fixation tasks. Amplitude, peak velocity and latency of upward, downward, and vertical saccades were calculated, together with square wave jerks (SWJ) number and amplitude during fixation. Correlations between VOG data and clinico-radiological features were investigated. Results NPH patients showed a significant (33.8%) increase in saccadic latency compared to HC, with no differences in saccadic amplitude and peak velocity. The number and amplitude of SWJ were also similar between NPH and HC groups. Saccadic latency was specifically associated with cognitive deficits, especially phonemic fluency and executive functions, in the NPH group. Conclusion This study characterized ocular dysfunction in NPH patients, demonstrating an increase of saccadic latency in comparison with HC, strongly associated with cognitive impairment. These results identified saccadic latency as a rapid and quantitative VOG biomarker of cognitive deficits in NPH, holding potential for repeated assessment of cognitive status over time. On the other hand, saccadic amplitude and velocity were not affected in NPH, thus suggesting their possible role in the differential diagnosis between NPH and neurodegenerative parkinsonian syndromes.

Oculomotor deficits are common in hereditary ataxia, but disproportionally neglected in clinical ataxia scales and as outcome measures for interventional trials. Quantitative assessment of oculomotor function has become increasingly available and thus applicable in multicenter trials and offers the opportunity to capture severity and progression of oculomotor impairment in a sensitive and reliable manner. In this consensus paper of the Ataxia Global Initiative Working Group On Digital Oculomotor Biomarkers, based on a systematic literature review, we propose harmonized methodology and measurement parameters for the quantitative assessment of oculomotor function in natural-history studies and clinical trials in hereditary ataxia. MEDLINE was searched for articles reporting on oculomotor/vestibular properties in ataxia patients and a study-tailored quality-assessment was performed. One-hundred-and-seventeen articles reporting on subjects with genetically confirmed ( n =1134) or suspected hereditary ataxia ( n =198), and degenerative ataxias with sporadic presentation ( n =480) were included and subject to data extraction. Based on robust discrimination from controls, correlation with disease-severity, sensitivity to change, and feasibility in international multicenter settings as prerequisite for clinical trials, we prioritize a core-set of five eye-movement types: (i) pursuit eye movements, (ii) saccadic eye movements, (iii) fixation, (iv) eccentric gaze holding, and (v) rotational vestibulo-ocular reflex. We provide detailed guidelines for their acquisition, and recommendations on the quantitative parameters to extract. Limitations include low study quality, heterogeneity in patient populations, and lack of longitudinal studies. Standardization of quantitative oculomotor assessments will facilitate their implementation, interpretation, and validation in clinical trials, and ultimately advance our understanding of the evolution of oculomotor network dysfunction in hereditary ataxias.

Purpose To observe and analyze the effects of orthokeratology in patients with convergence insufficiency, exophoria, and myopia. Methods Thirty patients (60 eyes) between 8 and 15 years old with myopia and convergence insufficiency exophoria treated with orthokeratology at the First Affiliated Hospital of the Baotou Medical College from December 2022 to December 2023 were prospectively enrolled. General information was gathered and examinations were performed at baseline and at 2 weeks and 1, 3, and 6 months after switching to orthokeratology lenses. Examinations included assessments of distance/near visual acuity, near point of convergence, distance and near horizontal phoria, near positive fusional vergence, and monocular amplitude of accommodation. Results The median age of the participants was 10 years (range: 8 to 15 years), and 40% were female. The baseline refractive error was −2.00 diopters (D) (range: −4.00 and −1.00 D). After 6 months of treatment, we found statistically significant differences in near point of convergence (95% confidence interval: −13.99 to −8.67), positive fusional vergence (95% confidence interval: 15.32 to 11.42), and monocular amplitude of accommodation (95% confidence interval: 6.62 to 4.51) compared with baseline. In addition, the mean pretreatment near horizontal phoria decreased from 6.83 ± 1.44 to −4.90 ± 1.29 prism diopters after the 6 months of treatment (95% confidence interval: −2.92 to −0.94). Conclusions This study showed that the use of orthokeratology lenses with an increased compression factor of 1.75 D may improve near point of convergence, positive fusional vergence, and monocular amplitude of accommodation for the treatment of convergence insufficiency with myopia. [J Pediatr Ophthalmol Strabismus. 2025;62(4):252–257.]