Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol.

Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions. In this pilot study protocol, we aim to investigate the effects of dipyridamole (a well-known enhancer of adenosinergic transmission) and caffeine (an adenosine receptor antagonist) on measures of cortical excitation and inhibition in response to TMS in patients with primary RLS. Initially, we will assess cortical excitability using both single- and paired-pulse TMS in patients with RLS. Then, based on the measures obtained, we will explore the effects of dipyridamole and caffeine, in comparison to placebo, on various TMS parameters related to cortical excitation and inhibition. Finally, we will evaluate the psycho-cognitive performance of RLS patients to screen them for cognitive impairment and/or mood-behavioral dysfunction, thus aiming to correlate psycho-cognitive findings with TMS data. Overall, this study protocol will be the first to shed lights on the neurophysiological mechanisms of RLS involving the modulation of the adenosine system, thus potentially providing a foundation for innovative "pharmaco-TMS"-based treatments. The distinctive TMS profile observed in RLS holds indeed the potential utility for both diagnosis and treatment, as well as for patient monitoring. As such, it can be considered a target for both novel pharmacological (i.e., drug) and non-pharmacological (e.g., neuromodulatory), "TMS-guided", interventions.

Exploring the Associated Genetic Causes of Diabetic Retinopathy as a Model of Inflammation in Retinal Diseases.

To investigate potential biomarkers and biological processes associated with diabetic retinopathy (DR) using transcriptomic and proteomic data. The OmicsPred PheWAS application was interrogated to identify genes and proteins associated with DR and diabetes mellitus (DM) at a false discovery rate (FDR)-adjusted p-value of <0.05 and also <0.005. Gene Ontology PANTHER analysis and STRING database analysis were conducted to explore the biological processes and protein interactions related to the identified biomarkers. The interrogation identified 49 genes and 22 proteins associated with DR and/or DM; these were divided into those uniquely associated with diabetic retinopathy, uniquely associated with diabetes mellitus, and the ones seen in both conditions. The Gene Ontology PANTHER and STRING database analyses highlighted associations of several genes and proteins associated with diabetic retinopathy with adaptive immune response, valyl-TRNA aminoacylation, complement activation, and immune system processes. Our analyses highlight potential transcriptomic and proteomic biomarkers for DR and emphasize the association of known aspects of immune response, the complement system, advanced glycosylation end-product formation, and specific receptor and mitochondrial function with DR pathophysiology. These findings may suggest pathways for future research into novel diagnostic and therapeutic strategies for DR.

Design of a new 3D printed all-in-one magnetic smartphone adapter for fundus and anterior segment imaging.

PURPOSE: To describe and validate a 3D-printed adapter tool which could be used with either a slit lamp or a condensing lens, interchangeable between devices through magnetic fastening, in order to provide physicians a quick, easy and effective method of obtaining clinical photos. MATERIALS AND METHODS: Three specialists, with at least 4-year experience in ophthalmology, gave a rate of image quality obtained by our device and the diagnostic confidence grade. The 3 specialists conducted each 13 or 14 examinations with the smartphone and magnetic adapter. At the end of evaluation, they rated with the Likert scale the ease of use of the device in obtaining clinical images of the anterior segment and ocular fundus respectively. RESULTS: Data of quality perception and confidence demonstrated high values not dissimilar to the "de visu" eye examination. Moreover the instrument we designed turned out to be very user friendly. CONCLUSION: Our adapter coupled with a modern smartphone was able to obtain 4k images and videos of anterior segment, central and peripheral fundus, in an easy and inexpensive way.

COVID-19-related retinal microvasculopathy and systemic implications in patients with severe disease: results from the Methuselah study.

Objectives: To assess the reversibility of retinal microvascular changes in the long term and to investigate the potential links with other vascular diseases of COVID-19. Methods: We designed a prospective multicenter observational study. Patients were enrolled from the Methuselah study cohort. Retinal vascular function was studied in these patients using optical coherence tomography angiography (OCTA); aortic stiffness was measured using aortic pulse wave velocity. These examinations were performed 1 (Visit 1) and 12 (Visit 2) months after the hospital discharge for severe COVID-19. A control subject group matched for age and sex was included to define normal values. Results: A total of 28 control subjects (56 eyes) and 25 patients (50 eyes) completed the scheduled OCTA assessment; 18 patients (36 eyes) also completed the macrovascular examination. Compared to controls, the vessel density of the superficial capillary plexus (SCP) was reduced, whereas the foveal avascular zone area was enlarged at Visit 1 (p = 0.016 and < 0.001, respectively) and was not modified after the 12-month follow-up in COVID-19 patients (p = 0.011 and 0.001, respectively). Higher inflammation and lower renal function during hospitalization were linked to higher aortic stiffness and reduced vessel density of the SCP 1 month after the acute phase of COVID-19. A slower recovery of aortic dysfunction was linked to worse retinal vascular outcomes at Visit 2. Conclusion: Retinal vascular alterations were not reversible 12 months after COVID-19 and were linked to inflammation and renal dysfunction during hospitalization as well as to aortic stiffness measured during follow-up.

Efficacy and Safety of Artificial Tears Containing Lipidure and Hypromellose for the Treatment of Moderate Dry Eye Disease in Contact Lens Wearers.

Background and Objectives: Dry eye disease (DED) affects 5-50% of the global population and deeply influences everyday life activities. This study compared the efficacy, tolerability, and safety of novel Respilac artificial tears containing lipidure and hypromellose (HPMC) with the widely used Nextal artificial tears, which are also HPMC-based, for the treatment of moderate DED in contact lenses (CL) wearers. Materials and Methods: In a prospective, single-center, randomized investigation, 30 patients aged ≥18 years, diagnosed with moderate DED, and wearing CL were randomly assigned to the Respilac (n = 15) or Nextal group (n = 15). Patients self-administrated one drop of Respilac or Nextal in both eyes three times daily for 21 days. Changes in the endpoint (visual analogue scale (VAS) score for ocular tolerability, symptom assessment in dry eye (SANDE) score, non-invasive first break-up time (NIF-BUT) results, tear analysis value, meibography results, and CL tolerability results were assessed, comparing treatment groups and time-point evaluations. Adverse events (AEs) were also recorded and evaluated. Results: VAS scores decreased with time (p < 0.001) in both groups, showing no statistically significant difference among them (p = 0.13). Improvements were also detected from screening to end-of-treatment, which were indicated by the SANDE scores for severity and frequency (p < 0.001) and by tear analysis results (p < 0.001) with no observed difference between the Nextal and Respilac arms. NIF-BUT, meibography, and CL tolerability values were shown to be non-significantly affected by treatment and time. There were no AEs detected in this study cohort. Conclusions: Respilac was confirmed to be effective, safe, and well-tolerated. Lipidure-based ophthalmic solution was shown not to be inferior to the currently used Nextal, however, showing improvements in DED symptoms. Within the existing literature, our study is one of the first to report that MPC plus HPMC-containing eye drops are an effective option for the treatment of moderate dry eye disease and desiccation damage prevention in contact lens wearers.

Reliability and accuracy of artificial intelligence ChatGPT in providing information on ophthalmic diseases and management to patients.

PURPOSE: To assess the accuracy of ophthalmic information provided by an artificial intelligence chatbot (ChatGPT). METHODS: Five diseases from 8 subspecialties of Ophthalmology were assessed by ChatGPT version 3.5. Three questions were asked to ChatGPT for each disease: what is x?; how is x diagnosed?; how is x treated? (x = name of the disease). Responses were graded by comparing them to the American Academy of Ophthalmology (AAO) guidelines for patients, with scores ranging from -3 (unvalidated and potentially harmful to a patient's health or well-being if they pursue such a suggestion) to 2 (correct and complete). MAIN OUTCOMES: Accuracy of responses from ChatGPT in response to prompts related to ophthalmic health information in the form of scores on a scale from -3 to 2. RESULTS: Of the 120 questions, 93 (77.5%) scored ≥ 1. 27. (22.5%) scored ≤ -1; among these, 9 (7.5%) obtained a score of -3. The overall median score amongst all subspecialties was 2 for the question "What is x", 1.5 for "How is x diagnosed", and 1 for "How is x treated", though this did not achieve significance by Kruskal-Wallis testing. CONCLUSIONS: Despite the positive scores, ChatGPT on its own still provides incomplete, incorrect, and potentially harmful information about common ophthalmic conditions, defined as the recommendation of invasive procedures or other interventions with potential for adverse sequelae which are not supported by the AAO for the disease in question. ChatGPT may be a valuable adjunct to patient education, but currently, it is not sufficient without concomitant human medical supervision.

Line-field confocal optical coherence tomography of eyelid margin growths: A case series.

BACKGROUND: The clinical differential diagnosis of lesions arising on the eyelid margin may be challenging and an unneeded surgical approach may have serious functional and aesthetic consequences. Nonetheless, early recognition and treatment of malignant tumors of the eyelid margin is mandatory. Line-field confocal optical coherence tomography (LC-OCT) is a novel tool for the in vivo, real-time skin imaging. OBJECTIVES: The aim of the study was to identify and analyze the LC-OCT features of a series of eyelid margin growths and to correlate these features with the histopathological findings. METHODS: Patients with eyelid margin growths who were scheduled for lesion excision underwent LC-OCT examination. Inclusion criteria were a challenging clinical aspect of the lesions and a clinical history of recent onset (up to 12 months). In all cases, the histopathological examination of the excised lesions was performed for the final diagnosis. RESULTS: A total of 31 lesions located on the upper (13 cases) or lower (18 cases) eyelid margin from 28 consecutive patients (male = 15, female = 13; mean age: 64.7 years, range: 44-87 years) were evaluated and excised. The histopathologic diagnoses were nodular basal cell carcinoma (BCC) (nine cases), squamous cell carcinoma (SCC) (three cases), compound nevus (four cases), dermal nevus (two cases), seborrheic keratosis (four cases), pyogenic granuloma (one case), trichilemmal cyst (three cases), and hidrocystoma (five cases). LC-OCT allowed the in vivo recognition of the main microscopic features of the examined lesions. CONCLUSIONS: LC-OCT represents a promising tool for the evaluation of eyelid margin lesions. Advantages of non-invasive diagnosis particularly relevant in such a sensitive region include a more correct planning of the treatment and, in case of surgery, the most appropriate surgical approach and, importantly, a correct timing of intervention.

Interdisciplinary Multidimensional Assessment of Transthyretin Amyloidosis before and after Tafamidis.

BACKGROUND: Clinically, there is considerable heterogeneity in the presentation of transthyretin amyloidosis (ATTR), which ranges from primarily cardiac and primarily neurologic to mixed disease, among other manifestations. Because of this complex presentation, the diagnosis and management of patients with ATTR are often challenging and should be performed in interdisciplinary centers specialized in amyloidosis. Here, we aimed to increase awareness of ATTR detection and pathophysiology through a multidimensional multiorgan approach. CASE REPORT: We reported on a 60-year-old man with wild-type ATTR who underwent a number of both basic and advanced cardiological and neurological investigations at baseline and after a treatment period with the TTR tetramer stabilizer, tafamidis. Several findings are provided here, some of which might be considered instrumental correlates of the patient's clinical improvement after therapy. CONCLUSIONS: Adequate awareness and prompt recognition of ATTR support early diagnosis and faster access to therapies, thereby slowing the progression and improving the prognosis. The need for a multidisciplinary alliance between specialists and the opportunity to perform, at least in selected cases, a set of specific examinations for a detailed assessment of ATTR patients can also provide valuable insights into the physiopathology and response to therapy of a disease as complex and intriguing as ATTR.