Usher syndrome Type 1-associated gene, pcdh15b, is required for photoreceptor structural integrity in zebrafish

Blindness associated with Usher Syndrome Type 1 (USH1) is typically characterized as rod photoreceptor degeneration, followed by secondary loss of cones. The mechanisms leading to blindness are unknown since most genetic mouse models only recapitulate auditory defects. We generated zebrafish mutants for one of the USH1 proteins, protocadherin-15b (pcdh15b), a putative cell adhesion molecule. Zebrafish pcdh15 is expressed exclusively in photoreceptors within calyceal processes (CPs), at the base of the outer segment (OS), and within the synapse. In our mutants, rod and cone photoreceptor integrity is compromised with early and progressively worsening abnormal OS disc growth and detachment, in part due to weakening CP contacts. These effects were attenuated or exacerbated by growth in dark and bright light conditions, respectively. We also describe novel evidence for structural defects in synapses of pcdh15 mutant photoreceptors. Cell death does not accompany these defects at early stages, suggesting that photoreceptor structural defects, rather than overt cell loss, may underlie vision deficits. Thus, we present the first genetic animal model of a pcdh15-associated retinopathy that can be used to understand the etiology of blindness in USH1.

Temporal Characteristics of Visual Processing in Amblyopia

PurposeAmblyopia affects not only spatial vision but also temporal vision. In this study, we aim to investigate temporal processing deficits in amblyopia.MethodsTwenty amblyopic patients (age: 27.0 ± 5.53 years, 15 males), and 25 normal observers (age: 25.6 ± 4.03 years, 15 males) were recruited in this study. Contrast thresholds in an orientation discrimination task in five target-mask stimulus onset asynchronies (SOA) conditions (16.7 ms, 33.4 ms, 50.0 ms, 83.4 ms, and ∞/no noise) were measured. An elaborated perceptual template model (ePTM) was fit to the behavioral data to derive the temporal profile of visual processing for each participant.ResultsThere were significant threshold differences between the amblyopic and normal eyes [F(1,43) = 10.6, p = 0.002] and a significant group × SOA interaction [F(2.75,118) = 4.98, p = 0.004], suggesting different temporal processing between the two groups. The ePTM fitted the data well (χ2 test, all ps > 0.50). Compared to the normal eye, the amblyopic eye had a lower template gain (p = 0.046), and a temporal window with lower peak and broader width (all ps < 0.05). No significant correlation was found between the observed temporal deficits and visual acuity in amblyopia (ps > 0.50). Similar results were found in the anisometropic amblyopia subgroup. No significant difference was found between the fellow eyes of the monocular amblyopia and the normal eyes.ConclusionAmblyopia is less efficient in processing dynamic visual stimuli. The temporal deficits in amblyopia, represented by a flattened temporal window, are likely independent of spatial vision deficits.

A Worthwhile Collaboration: Integrating Optometry and Occupational Therapy in the Treatment of Children

Background: Vision deficits are highly prevalent in children with neurodevelopmental disorders including those with motor delays, learning and reading difficulties, and maladaptive behaviors. These deficits can interfere with their participation and performance in everyday life activities and therefore, require a comprehensive approach to therapy. As such, optometrists and occupational therapists are an optimal team to provide interprofessional collaborative care, reported in research as best practice, in the treatment of these children. However, little is known about the long-called-for collaboration between these professions. The purpose of this study was to explore factors and implications associated with a collaborative practice between optometrists and occupational therapists in the co-management of vision deficits in the pediatric population. Methods: A qualitative, descriptive design was employed to explore perceptions of collaborative practice among teams of optometrists and occupational therapists in the remedial care of children with visual deficits. Following IRB approval, co-located optometrists and occupational therapists were recruited for this study. Semistructured interviews served as the primary data collection tool to investigate the factors and implications of collaborative practice. Results: Eleven professionals provided informed consent and took part in this study, including five occupational therapists and six optometrists. Following thematic analysis, four overarching themes emerged including 1) professional boundaries, 2) co-located, integrated practice, 3) professional growth, and 4) improved patient care. Participants indicated that although barriers exist, exercising humility, upholding patient-centered focus, maintaining mutual respect, communicating frequently, and co-location were factors that enable collaboration. Positive outcomes related to both the provider and the patient were further highlighted supporting the interprofessional collaboration between these professionals. Conclusions: The findings of this qualitative study add to the body of evidence underpinning interprofessional collaborative practice. Furthermore, this study supports the coordination of care, through optometry and occupational therapy collaboration, in the treatment of visual deficits in children with special needs.

Col11a1a Expression Is Required for Zebrafish Development

The autosomal dominant chondrodystrophies, the Stickler type 2 and Marshall syndromes, are characterized by facial abnormalities, vision deficits, hearing loss, and articular joint issues resulting from mutations in COL11A1. Zebrafish carry two copies of the Col11a1 gene, designated Col11a1a and Col11a1b. Col11a1a is located on zebrafish chromosome 24 and Col11a1b is located on zebrafish chromosome 2. Expression patterns are distinct for Col11a1a and Col11a1b and Col11a1a is most similar to COL11A1 that is responsible for human autosomal chondrodystrophies and the gene responsible for changes in the chondrodystrophic mouse model cho/cho. We investigated the function of Col11a1a in craniofacial and axial skeletal development in zebrafish using a knockdown approach. Knockdown revealed abnormalities in Meckel’s cartilage, the otoliths, and overall body length. Similar phenotypes were observed using a CRISPR/Cas9 gene-editing approach, although the CRISPR/Cas9 effect was more severe compared to the transient effect of the antisense morpholino oligonucleotide treatment. The results of this study provide evidence that the zebrafish gene for Col11a1a is required for normal development and has similar functions to the mammalian COL11A1 gene. Due to its transparency, external fertilization, the Col11a1a knockdown, and knockout zebrafish model systems can, therefore, contribute to filling the gap in knowledge about early events during vertebrate skeletal development that are not as tenable in mammalian model systems and help us understand Col11a1-related early developmental events.

Acute presentation of idiopathic intracranial hypertension with severe vision deficits

Fulminant idiopathic intracranial hypertension is a rare presentation of idiopathic intracranial hypertension in which visual decline occurs within 4 weeks of initial symptom presentation. Idiopathic intracranial hypertension usually presents with headaches, visual disturbances, and in women who are overweight. We present a case of idiopathic intracranial hypertension in which a female patient presented with rapid, severe vision loss within 8 days of symptom presentation and no other idiopathic intracranial hypertension symptoms. This case highlights a rare presentation of Fulminant idiopathic intracranial hypertension and the need for a quick diagnosis and treatment to preserve vision.

Disseminated blastomycosis presenting as a retro-orbital mass

A 43-year-old man with history of non-Hodgkins’ lymphoma presented with unilateral eye swelling, pain and vision deficits which had been progressive over 2 months. Symptoms followed a presumed bacterial pneumonia 4 months prior. Imaging demonstrated retro-orbital soft tissue swelling with bony erosion concerning for a mass; surgical decompression was performed with histology confirming disseminated Blastomyces dermatitidis. Symptoms responded rapidly to antifungal therapy with amphotericin followed by itraconazole. Orbital dissemination of blastomycosis is extremely rare; accurate diagnosis requires tissue biopsy to facilitate timely targeted therapy and minimise morbidity.

060 Impaired color discrimination is associated with hallucinations in dementia with lewy bodies

IntroductionEmerging evidence indicates that color discrimination impairments can predict the development of dementia across a range of prodromal Lewy body conditions. However, color vision deficits are not seen uniformly in patients with Dementia with Lewy Bodies (DLB), suggesting a more nuanced association. Visual hallucinations(VH) represent a discriminating feature of DLB, and recent evidence implicates visual pathway dysfunction as a significant contributor to this phenomenon. We therefore hypothesized that color impairment will more closely associate with VH in DLB rather than general cognition.MethodsIn this study, we examined the relationship between color vision impairment and VH, along with other clinical and neuropsychological features in 24 patients with DLB alongside 25 age-matched controls. Color discrimination was assessed using the Farnsworth-Munsell-100 Hue (FM-100) test.ResultsColor discrimination impairment was seen in 16/24 DLB participants (67%) with a higher error score relative to controls(p=0.001). We demonstrate for the first time a strong association between color discrimination errors and both the presence and severity of VH in DLB based on clinician-derived(p=0.008) and questionnaire-derived(p=0.03) measures. Correlation with clinical and neuropsychological variables revealed that color discrimination is significantly related to visuospatial impairment(p=0.02) but not to global measures of cognition, motor severity, age or disease duration. Factor analysis confirmed a unique relationship between color discrimination, visual hallucinations and visuospatial function.ConclusionOur results suggest that color impairments may be a specific biomarker of visual hallucinations and associated visuoperceptual deficits in evolving Lewy body disorders rather than dementia per se and thus providing insight into a shared pathophysiological substrate.