SILICONE FINE-NEEDLE ASPIRATION RETINAL BIOPSY: A Novel Surgical Technique for Vitreoretinal Lymphoma.

PURPOSE: To describe a 41-gauge silicone fine-needle aspiration biopsy (S-FNAB) technique and assess its value in diagnosing primary vitreoretinal lymphoma (PVRL). METHODS: Retrospective review of seven consecutive patients who underwent vitreous biopsy (VB) and 41-gauge S-FNAB of retinal/subretinal lesions in a single tertiary center between January 2012 and March 2023. RESULTS: Of seven patients, S-FNAB confirmed the diagnosis of PVRL in six patients. In five of those patients, both VB and retinal/subretinal S-FNAB (performed at the same procedure) yielded positive results, with the retinal thickness at the biopsy site as small as 231 µm. Four of these five patients had one or more previous negative VB. In one patient, S-FNAB yielded positive results despite a negative VB. Silicone fine-needle aspiration biopsy failed to confirm positive VB for PVRL in the remaining patient. The time from symptom onset to diagnosis of PVRL ranged from 18 days to 26 months. There were no severe complications associated with the procedure. CONCLUSION: Silicone fine-needle aspiration biopsy might be a valuable method for obtaining a sufficient sample of viable cells to diagnose PVRL. It can be performed as a primary procedure along with VB. Further studies are warranted to determine where this technique could be most advantageous.

Disease Progression in CNGA3 and CNGB3 Retinopathy; Characteristics of Slovenian Cohort and Proposed OCT Staging Based on Pooled Data from 126 Patients from 7 Studies.

Achromatopsia has been proposed to be a morphologically predominately stable retinopathy with rare reports of progression of structural changes in the macula. A five-grade system of optical coherence tomography (OCT) features has been used for the classification of structural macular changes. However, their association with age remains questionable. We characterized the Slovenian cohort of 12 patients with pathogenic variants in CNGA3 or CNGB3 who had been followed up with OCT for up to 9 years. Based on observed structural changes in association with age, the following four-stage classification of retinal morphological changes was proposed: (I) preserved inner segment ellipsoid band (Ise), (II) disrupted ISe, (III) ISe loss and (IV) ISe and RPE loss. Data from six previously published studies reporting OCT morphology in CNGA3 and CNGB3 patients were additionally collected, forming the largest CNGA3/CNGB3 cohort to date, comprising 126 patients aged 1-71 years. Multiple regression analysis showed a significant correlation of OCT stage with age (p < 0.001) and no correlation with gene (p > 0.05). The median ages of patients with stages I-IV were 12 years, 23 years, 27 years and 48 years, respectively, and no patient older than 50 years had continuous ISe. Our findings suggest that achromatopsia presents with slowly but steadily progressive structural changes of the macular outer retinal layers. However, whether morphological changes in time follow the proposed four-stage linear pattern needs to be confirmed in a long-term study.

Automated Visual Acuity Evaluation Based on Preferential Looking Technique and Controlled with Remote Eye Tracking.

OBJECTIVE: To establish an automated visual acuity test (AVAT) for infants, based on preferential looking technique and controlled with remote eye tracking. To validate the AVAT in a group of healthy children. To compare AVAT visual acuity (VA) values with corresponding VA values acquired with standard tests (ST). METHODS: ST, adapted for age (Keeler Acuity Cards in preverbal children and LEA symbols in verbal children), was performed to obtain monocular VA in a group of 36 healthy children. During AVAT, 9 different stimuli with grating circles that matched spatial frequencies of 9 Keeler Acuity Cards (ranging between 0.29 and 14.5 cycles per degree) were projected on a screen. Three repetitions of each stimulus were shown during 9-s intervals, interchanging with an attention grabber. The remote eye tracker was used to evaluate the proportion of time a child spent looking at each grating circle compared to a homogeneous gray background that matched the grating stimuli in average luminance. From this proportion of time, child's binocular VA was evaluated. RESULTS: Ninety-seven percent (35/36) of healthy children successfully completed ST and AVAT. There was an agreement between the results of an ST and AVAT, with Lin's concordance coefficient being 0.53 (95% CI = 0.31-0.72). A tendency was observed toward VA overestimation on AVAT for children with VA >0.4 logMAR on ST and toward VA underestimation on AVAT for children with VA ≤0.4 logMAR on ST. CONCLUSIONS: AVAT requires a minimally skilled investigator. The evaluation of better eye monocular VA on ST and binocular VA on AVAT was comparable for healthy children.

Morphological and functional parameters in X-linked retinoschisis patients-A multicentre retrospective cohort study.

Introduction: X-linked retinoschisis (XLRS) is a potential target for gene supplementation approaches. To establish potential structural and functional endpoints for clinical trials, a comprehensive understanding of the inter-eye symmetry, relationship between structural and functional parameters, and disease progression is vital. Methods: In this retrospective multicentre study, 118 eyes of 59 XLRS patients with RS1 mutations were assessed. Information from center databases included: RS1 variant; age at presentation; best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular volume (MV) at presentation and at the last follow up; full-field electroretinogram (ERG) findings; presence of peripheral retinoschisis and complications (vitreous hemorrhage, retinal detachment); treatment with systemic or topical carbonic anhydrase inhibitors (CAI). Results: Inter-eye symmetry revealed strong correlation in CRT (r = 0.77; p < 0.0001) and moderate correlations in MV (r = 0.51, p < 0.0001) and BCVA (r = 0.49; p < 0.0001). Weak or no correlations were observed between BCVA and structural parameters (CRT, MV). Peripheral retinoschisis was observed in 40 (68%), retinal detachment in 9 (15%), and vitreous hemorrhage in 5 (8%) patients, respectively. Longitudinal examinations (mean, 4.3 years) showed no BCVA changes; however, a reduction of the CRT (p = 0.02), and MV (p = 0.01) was observed. Oral and/or topical CAI treatment did not significantly alter the CRT (p = 0.34). Discussion: The XLRS phenotype demonstrates a strong CRT symmetry between the eyes within individual patients and stable BCVA over several years. BCVA exhibits a weak correlation with the morphological parameters of retinal thickness (CRT MV). In our cohort, longitudinal functional changes were not significant, likely attributed to the short average follow-up period. Furthermore, CAI treatment didn't influence both morphological and functional outcomes.

Various clinical presentations of uveitis associated with durvalumab treatment.

BACKGROUND: Immune checkpoint inhibitors (ICI) are becoming increasingly common in treating several cancer types. Durvalumab is a human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80 and has recently been approved for the treatment of extensive-stage small-cell lung cancer (ES-SCLC) and locally advanced unresectable (NSCLC). The present review aimed to analyse immune-mediated uveitis, secondary to durvalumab treatment, through a review of the literature and a presentation of two clinical cases. PATIENTS AND METHODS: A literature review using PubMed search was conducted to identify cases of uveitis secondary to durvalumab and cases of uveitis with optic disc oedema secondary to ICI use that were reported prior to November 14, 2021. Additionally, we report two cases of uveitis consequent on durvalumab treatment. RESULTS: Five cases of uveitis secondary to durvalumab use were identified in the literature. Anterior, posterior uveitis and vasculitis were reported. Additionally, we present a case of bilateral intermediate uveitis with bilateral optic disc oedema and a case of bilateral posterior uveitis. Our further search revealed 12 cases of uveitis with optic disc oedema secondary to ICI use, with the majority of cases reported secondary to PD-1 inhibitors. CONCLUSIONS: Rarely reported, uveitis secondary to durvalumab can present various clinical pictures and requires a thorough diagnostic workup. Once the diagnosis is established, treatment, commonly with a local or systemic corticosteroid, should be adapted to the severity of the inflammation.

Repurposing beta-3 adrenergic receptor agonists for Alzheimer's disease: beneficial effects in a mouse model.

BACKGROUND: Old age, the most important risk factor for Alzheimer's disease (AD), is associated with thermoregulatory deficits. Brown adipose tissue (BAT) is the main thermogenic driver in mammals and its stimulation, through ß3 adrenergic receptor (ß3AR) agonists or cold acclimation, counteracts metabolic deficits in rodents and humans. Studies in animal models show that AD neuropathology leads to thermoregulatory deficits, and cold-induced tau hyperphosphorylation is prevented by BAT stimulation through cold acclimation. Since metabolic disorders and AD share strong pathogenic links, we hypothesized that BAT stimulation through a ß3AR agonist could exert benefits in AD as well. METHODS: CL-316,243, a specific ß3AR agonist, was administered to the triple transgenic mouse model of AD (3xTg-AD) and non-transgenic controls from 15 to 16 months of age at a dose of 1 mg/kg/day i.p. RESULTS: Here, we show that ß3AR agonist administration decreased body weight and improved peripheral glucose metabolism and BAT thermogenesis in both non-transgenic and 3xTg-AD mice. One-month treatment with a ß3AR agonist increased recognition index by 19% in 16-month-old 3xTg-AD mice compared to pre-treatment (14-month-old). Locomotion, anxiety, and tau pathology were not modified. Finally, insoluble Aß42/Aß40 ratio was decreased by 27% in the hippocampus of CL-316,243-injected 3xTg-AD mice. CONCLUSIONS: Overall, our results indicate that ß3AR stimulation reverses memory deficits and shifts downward the insoluble Aß42/Aß40 ratio in 16-month-old 3xTg-AD mice. As ß3AR agonists are being clinically developed for metabolic disorders, repurposing them in AD could be a valuable therapeutic strategy.