SLC38A8 mutations result in arrested retinal development with loss of cone photoreceptor specialization

Foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis is an autosomal recessive disorder arising from SLC38A8 mutations. SLC38A8 is a putative glutamine transporter with strong expression within the photoreceptor layer in the retina. Previous studies have been limited due to lack of quantitative data on retinal development and nystagmus characteristics. In this multi-centre study, a custom-targeted next generation sequencing (NGS) gene panel was used to identify SLC38A8 mutations from a cohort of 511 nystagmus patients. We report 16 novel SLC38A8 mutations. The sixth transmembrane domain is most frequently disrupted by missense SLC38A8 mutations. Ninety percent of our cases were initially misdiagnosed as PAX6-related phenotype or ocular albinism prior to NGS. We characterized the retinal development in vivo in patients with SLC38A8 mutations using high-resolution optical coherence tomography. All patients had severe grades of arrested retinal development with lack of a foveal pit and no cone photoreceptor outer segment lengthening. Loss of foveal specialization features such as outer segment lengthening implies reduced foveal cone density, which contributes to reduced visual acuity. Unlike other disorders (such as albinism or PAX6 mutations) which exhibit a spectrum of foveal hypoplasia, SLC38A8 mutations have arrest of retinal development at an earlier stage resulting in a more under-developed retina and severe phenotype

Coincident PAMM and AMN and Insights Into a Common Pathophysiology

Purpose: To analyze imaging characteristics and the clinical course of patients demonstrating coincident lesions of paracentral acute middle maculopathy (PAMM) and acute macular neuroretinopathy (AMN) in the same eye. Design: Retrospective, observational case series. Methods: Lesions from patients presenting with coincident PAMM and AMN in the same eye were evaluated with multimodal imaging including optical coherence tomography (OCT). The association with ocular and systemic findings was also investigated. Results: Fifteen subjects (17 eyes) were included in the study. The mean age was 44.4 ± 15.3 years and the follow-up period ranged from 1 to 32 weeks (mean, 11.9 ± 11.4 weeks). The mean visual acuity was 0.8 ± 0.6 logarithm of minimal angle of resolution (Snellen equivalent 20/126) at baseline and 0.3 ± 0.4 logarithm of minimal angle of resolution (Snellen equivalent 20/40) at the last follow-up. PAMM and AMN lesions occurred in the setting of Purtscher's retinopathy (4 eyes, 3 patients), retinal vein occlusion (7 eyes, 7 patients), central retinal artery occlusion (1 eye, 1 patient), and idiopathic retinal vasculitis (1 eye, 1 patient). In 4 eyes (3 patients), an association with other ocular disorders was not identified as evaluated with multimodal imaging. Of the total cohort, 11 eyes (64.7%) showed extension of the AMN hyperreflective bands in Henle's fiber layer with a Z-shaped morphology on OCT B-scan. Conclusions: The presence of coincident PAMM and AMN suggests a common pathophysiologic etiology. This may be the result of retinal vein impairment and hypoperfusion at the level of the deep retinal capillary plexus possibly leading to injury to the Müller glia or photoreceptors in Henle's fiber layer

Coincident PAMM and AMN and insights into a common pathophysiology

Purpose: To analyze imaging characteristics and the clinical course of patients demonstrating coincident lesions of paracentral acute middle maculopathy (PAMM) and acute macular neuroretinopathy (AMN) in the same eye. Design: Retrospective, observational case series. Methods: Lesions from patients presenting with coincident PAMM and AMN in the same eye were evaluated with multimodal imaging including optical coherence tomography (OCT). The association with ocular and systemic findings was also investigated. Results: Fifteen subjects (17 eyes) were included in the study. The mean age was 44.4 ± 15.3 years and the follow-up period ranged from 1 to 32 weeks (mean, 11.9 ± 11.4 weeks). The mean visual acuity was 0.8 ± 0.6 logarithm of minimal angle of resolution (Snellen equivalent 20/126) at baseline and 0.3 ± 0.4 logarithm of minimal angle of resolution (Snellen equivalent 20/40) at the last follow-up. PAMM and AMN lesions occurred in the setting of Purtscher's retinopathy (4 eyes, 3 patients), retinal vein occlusion (7 eyes, 7 patients), central retinal artery occlusion (1 eye, 1 patient), and idiopathic retinal vasculitis (1 eye, 1 patient). In 4 eyes (3 patients), an association with other ocular disorders was not identified as evaluated with multimodal imaging. Of the total cohort, 11 eyes (64.7%) showed extension of the AMN hyperreflective bands in Henle's fiber layer with a Z-shaped morphology on OCT B-scan. Conclusions: The presence of coincident PAMM and AMN suggests a common pathophysiologic etiology. This may be the result of retinal vein impairment and hypoperfusion at the level of the deep retinal capillary plexus possibly leading to injury to the Müller glia or photoreceptors in Henle's fiber layer. © 2021 Elsevier Inc

Clinical and Morphologic Characteristics of Perivenular Fernlike Leakage on Ultrawide-field Fluorescein Angiography

Purpose: To analyze the spectrum of the perivenular fernlike leakage on ultrawide-field fluorescein angiography (UWFA) and discuss its potential implications in the current understanding of the retinal venous outflow. Design: Retrospective, observational case series. Participants: Eyes presenting with fernlike patterns of dye leakage on UWFA were included in this study. Methods: Analysis of the clinical characteristics and multimodal imaging findings using UWFA and wide-angle swept-source OCT-angiography (SS-OCTA). Main Outcome Measures: The disease spectrum, anatomic origin, and clinical implications of this fernlike leakage. Results: Multimodal retinal images from 40 eyes of 29 patients with fernlike leakage on UWFA were studied. The underlying etiologies included a wide range of inflammatory disorders, including pars planitis (18 eyes) and central retinal vein occlusion (2 eyes). On UWFA, the fernlike leakage originated from the retinal capillaries and venules directly adjacent to the veins and spared the periarterial zone. This perivenular fernlike leakage involved the far periphery in all cases and progressed more diffusely and centripetally in cases with more severe intraocular inflammation. On wide-angle SS-OCTA, the impairment of deep capillary plexus (DCP) flow signals precisely colocalized with the perivenular fernlike leakages identified on UWFA. Conclusions: The fernlike leakage on UWFA refers to the distinctive perivenular dye leakage that originates from the retinal capillaries and venules. Multimodal imaging correlation suggests that the predominant impairment is at the level of the DCP. The axial symmetry of the fernlike leakage with the veins and sparing of the periarterial zone may support the dominant venous role of the DCP

BACILLARY LAYER DETACHMENT

To clarify the histologic basis of bacillary layer detachment (BALAD) through a review of current literature and an analysis of retinal imaging. Methods: We reviewed the literature for previous reports of BALAD. An analysis of retinal images was performed to support anatomic conclusions. Results: A total of 164 unique patients with BALAD on optical coherence tomography (OCT) were identified from the published literature. Twenty-two underlying etiologies, all associated with subretinal exudation, were identified. Forty-one different OCT terminologies were found. The defining OCT feature of BALAD was a split at the level of the photoreceptor inner segment myoid creating a distinctive intraretinal cavity. Resolution of BALAD was followed by a rapid restoration of the ellipsoid zone. Histology of age-related macular degeneration eyes suggests that individual photoreceptors can shed inner segments. Further, detachment of the entire layer of inner segments is a common postmortem artefact. We propose that BALAD occurs when outwardly directed forces promoting attachment of photoreceptor outer segments to the retinal pigment epithelium exceed the tensile strength of the photoreceptor inner segment myoid. Conclusion: Our review serves to strengthen the OCT nomenclature “bacillary layer detachment”, based on specific reflectance information obtained by OCT and previously published histologic observations

Quantitative CT Extent of Lung Damage in COVID-19 Pneumonia Is an Independent Risk Factor for Inpatient Mortality in a Population of Cancer Patients: A Prospective Study

International audienceBackground: CT lung extent has emerged as a potential risk factor of COVID-19 pneumonia severity with mainly semiquantitative assessment, and outcome was not assessed in the specific oncology setting. The main goal was to evaluate the prognostic role of quantitative assessment of the extent of lung damage for early mortality of patients with COVID-19 pneumonia in cancer patients. Methods: We prospectively included consecutive cancer patients with recent onset of COVID-19 pneumonia assessed by chest CT between March 15, 2020, and April 20, 2020, and followed until May 1, 2020. Demographic, clinical, laboratory test data and imaging findings were recorded. Quantitative chest CT assessment of COVID-19 pneumonia was based on the density distribution of lung lesions using a freely available software recently released (Myrian XP-Lung). The association between extent of lung damage and overall survival was studied by univariate and multivariate Cox analysis. The Uno C-index was used to assess the discriminatory value of the quantitative CT extent of lung damage. Results: Seventy cancer patients with chest CT evidence of COVID-19 were included. After a median follow-up of 25 days, 17 patients (24%) had died. The median quantitative chest CT extent of COVID-19 was 20% (IQR = 14–35, range = 3–59) for non-survivors vs. 10% (IQR = 6–15, range = 2–55) for survivors (p = 0.002). The extent of COVID-19 pneumonia was correlated with inpatient management (p = 0.003) and oxygen therapy requirements (p < 0.001). Independent factors associated with death were performance status (PS) ≥2 (HR = 3.9, 95% CI = [1.1–13.8] p = 0.04) and extent of COVID-19 pneumonia ≥30% (HR = 12.0, 95% CI = [2.2–64.4] p = 0.004). No differences were found regarding the histology of cancer, cancer stage, metastases sites, or type of oncologic treatment between the survivor and non-survivor groups. The cross-validated Uno C-index of the model including PS and extent of COVID-19 pneumonia was 0.83, 95% CI = [0.73–0.93]. Conclusions: The quantitative chest CT extent of COVID-19 pneumonia was a strong independent prognostic factor of early inpatient mortality in a population of cancer patients

Surface guided radiation therapy: An international survey on current clinical practice.

Introduction Surface Guided Radiation Therapy (SGRT) is being increasingly implemented into clinical practice across a number of techniques and irradiation-sites. This technology, which is provided by different vendors, can be used with most simulation- and delivery-systems. However, limited guidelines and the complexity of clinical settings have led to diverse patterns of operation. With the aim to understand current clinical practice a survey was designed focusing on specifics of the clinical implementation and usage. Materials and methods A 32-question survey covered: type and number of systems, quality assurance (QA), clinical workflows, and identification of strengths/limitations. Respondents from different professional groups and countries were invited to participate. The survey was distributed internationally via ESTRO-membership, social media and vendors. Results Of the 278 institutions responding, 172 had at least one SGRT-system and 136 use SGRT clinically. Implementation and QA were primarily based on the vendors' recommendations and phantoms. SGRT was mainly implemented in breast RT (116/136), with strong but diverse representation of other sites. Many (58/135) reported at least partial elimination of skin-marks and a third (43/126) used open-masks. The most common imaging protocol reported included the combination of radiographic imaging with SGRT. Patient positioning (115/136), motion management (104/136) and DIBH (99/136) were the main applications.Main barriers to broader application were cost, system integration issues and lack of demonstrated clinical value. A lack of guidelines in terms of QA of the system was highlighted. Conclusions This overview of the SGRT status has the potential to support users, vendors and organisations in the development of practices, products and guidelines