Assessment of ocular involvement in transthyretin-related familial amyloidosis with polyneuropathy (FAP) in a large cohort of Portuguese patients. We reviewed the medical records of 513 Portuguese FAP mutation carriers, at the Ophthalmology Service, Centro Hospitalar do Porto, between 1 January 2008 and 31 January 2013. Abnormal conjunctiva vessels (ACV), Schirmer test, tear break-up time (TBUT), amyloid deposition on the iris (DAI), scalloped iris, amyloid deposition on the anterior capsule of the lens (DAL), vitreous amyloidosis, retinal amyloid angiopathy and glaucoma were evaluated and registered. Of the 513 carriers, 477 (93%) had clinical systemic disease with a median duration of 9.3 (5.1-13.7) years and 247 were men. Of these, 343 (72%) had been liver transplanted, on median of 6.6 (3.3-10.8) years before inclusion in this study. No ocular abnormalities were identified in the asymptomatic carriers (7%). The abnormalities observed with decreasing frequency were abnormal TBUT (379 patients, 79.5%, 751 eyes), abnormal Schirmer test (320 patients, 67%, 635 eyes), DAI (183 patients, 38.4%, 350 eyes), DAL (157 patients, 32.9%, 308 eyes), scalloped iris (133 patients, 27.9%, 238 eyes), glaucoma (97 patients, 20%, 165 eyes), vitreous amyloidosis (83 patients, 17.4%, 139 eyes), ACV (68 patients, 14%, 136 eyes) and amyloidotic retinal angiopathy (21 patients, 4%, 32 eyes). Patients with abnormal Schirmer test (p < 0.001), scalloped iris (p = 0.006) and vitreous amyloidosis (p = 0.007) were significantly older than the others. According to their age of onset of systemic disease, the patients have been split into early-onset (50 years old) and asymptomatic carriers. We observed a statistically significant difference in the prevalence of ACV (p = 0.045) and of an abnormal Schirmer test (p = 0.004) between groups. Transplanted patients have a significantly higher prevalence of DAI (p = 0.001), DAL (p = 0.009) and vitreous amyloidosis (p = 0.025) than non-transplanted patients. Of the 165 eyes with glaucoma, 92.1% had scalloped iris (p < 0.001) and of 32 eyes with retinal amyloidotic angiopathy, 68.8% had vitreous amyloidosis (p < 0.001). All prevalences increased with time of disease. The earliest ocular manifestations were abnormal Schirmer test and abnormal TBUT (12% and 17% at 5 years of clinical disease) and the least prevalent was retinal amyloid angiopathy (8% at 15 years of clinical disease). Ocular disorders in FAP patients are common, and their prevalence increases with disease duration. Prevalence is influenced by several factors, such as the age at onset of FAP and liver transplantation.

Evaluation of the impact of liver transplantation in the natural history of ocular disorders in familial amyloidotic polyneuropathy (FAP) amyloidosis TTR V30M related (ATTR V30M) patients. A clinical, retrospective and cross-sectional study of 64 Portuguese FAP ATTR V30M patients was carried out between January 2005 and December 2011. Thirty-two liver transplanted patients (both eyes) aged 39.6-53.8 years old, 32/32 male/female, were paired with an equal number of non-transplanted patients, matching for age, gender, age at onset, disease duration and gender of transmitting parent. Intervention or observation procedure: Routine ophthalmological observation. Slit-lamp observation for abnormal conjunctival vessels (ACV), tears break-up time, iris, lens; fundus observation for vitreous, retina and optic disc; Schirmer test. Liver transplantation had no influence on tears break-up time, deposition of amyloid on the iris and retinal amyloid angiopathy. Slight, non-statistically significant protective effects of liver transplantation were noted in the first years for some ocular manifestations (ACV and scalloped iris), except for the abnormal Schirmer test, which was significantly more prevalent in non-transplanted patients' eyes (81% versus 56%, p = 0.002). On the other hand, deposition of amyloid on the lens, vitreous amyloidosis and glaucoma were apparently more common in transplanted patients. Those differences tended to disappear with time. Ocular manifestations of FAP were not influenced by liver transplantation in a meaningful way. Both transplanted and non-transplanted FAP patients need similar regular follow-up due to long-term risk of serious ocular disease.

Nowadays, Artificial Intelligence (AI) and its subfields, Machine Learning (ML) and Deep Learning (DL), are used for a variety of medical applications. It can help clinicians track the patient’s illness cycle, assist with diagnosis, and offer appropriate therapy alternatives. Each approach employed may address one or more AI problems, such as segmentation, prediction, recognition, classification, and regression. However, the amount of AI-featured research on Inherited Retinal Diseases (IRDs) is currently limited. Thus, this study aims to examine artificial intelligence approaches used in managing Inherited Retinal Disorders, from diagnosis to treatment. A total of 20,906 articles were identified using the Natural Language Processing (NLP) method from the IEEE Xplore, Springer, Elsevier, MDPI, and PubMed databases, and papers submitted from 2010 to 30 October 2021 are included in this systematic review. The resultant study demonstrates the AI approaches utilized on images from different IRD patient categories and the most utilized AI architectures and models with their imaging modalities, identifying the main benefits and challenges of using such methods.

Background: To evaluate biomechanical parameters of the cornea provided by Corvis ST in patients with ocular hypertension, primary open-angle glaucoma, and amyloidotic glaucoma and to compare with healthy controls. Methods: This was a cross-sectional study of patients with ocular hypertension, primary open-angle glaucoma, and amyloidotic glaucoma that underwent Corvis ST imaging. Primary outcome was the comparison of corneal biomechanical parameters between study groups after adjusting for age, gender, Goldmann intraocular pressure (GAT-IOP), and prostaglandin analogues medication. Secondary outcome was the comparison of different TOP measurements in each group. Results: One hundred and eighty-three eyes from 115 patients were included: 61 with primary open-angle glaucoma, 32 with amyloidotic glaucoma, 37 with ocular hypertension and 53 were healthy controls. Amyloidotic glaucoma group had smaller radius (p=0.025), lower deflection amplitude at highest concavity (p=0.019), and higher integrated radius (p=0.014) than controls. Ocular hypertension group had higher stiffness parameter at first applanation (p=0.043) than those with primary open-angle glaucoma, and higher stress-strain index (p=0.049) than those with amyloidotic glaucoma. Biomechanically corrected intraocular pressure was significantly lower than Goldmann intraocular pressure in group with primary open-angle glaucoma (p=0.005) and control group (p=0.013), and Goldmann intraocular pressure adjusted for pachymetry in group with primary open-angle glaucoma (p=0.01). Conclusion: Eyes with amyloidotic glaucoma have more deformable corneas, while eyes with ocular hypertension have less deformable corneas. These findings may be linked to the susceptibility to glaucomatous damage and progression. There were significant differences between Goldmann applanation tonometry and biomechanically corrected intraocular ocular pressure provided by Corvis ST.

Glaucoma is one of the leading causes of permanent vision loss worldwide and has a profound impact on patients’ quality of life. Vision impairment is strongly associated with several psychiatric disorders, like depression, anxiety, and sleep problems. These psychiatric issues are often exacerbated by the gradual, irreversible, and typically silent progression of the disease, contributing to increased mental health challenges for affected individuals. A systematic review was conducted following PRISMA guidelines across six different databases (CINAHL, MEDLINE, PsycINFO, Web of Science, Scopus, and the Cochrane Library) and one gray literature source (Google Scholar), covering the period from 2013 to 2024. Twenty-nine studies involving a total of 13,326,845 subjects were included in the synthesis, highlighting a considerable prevalence of psychiatric disorders among glaucoma patients. Depression and anxiety were the most common conditions identified, with depression rates ranging from 6.6% to 57% and anxiety from 12.11% to 49%. Other less frequent but still significant conditions like sleep disorders, psychosis, dementia, and post-traumatic stress disorder were also observed. The findings also indicated that psychiatric severity was influenced by socio-demographic factors, glaucoma severity, and treatment duration. Given the high occurrence of psychiatric pathologies among individuals with glaucoma, it is essential to develop comprehensive care strategies that address both eye and mental health needs. Multidisciplinary collaboration among ophthalmologists, psychiatrists, psychologists, and primary care physicians is crucial for developing personalized treatment plans that effectively manage both the ocular and psychological aspects of the disease.

Familial amyloidotic polyneuropathy, ATTRV30M (p. TTRV50M) amyloidosis, is a neurodegenerative disease characterized by systemic extracellular amyloid deposition of a mutant transthyretin, TTR V30M. Anemia, with low erythropoietin (EPO) levels and spared kidney function, affects about 25% of symptomatic patients, suggesting a blockage of EPO-producing cells. Early non-fibrillar TTR aggregates are highly cytotoxic, inducing oxidative stress, the expression of apoptosis-related molecules and secretion of pro-inflammatory cytokines, factors capable of inhibiting EPO production. Low EPO levels in these patients are not related to renal amyloid deposition or the presence of circulating TTR V30M. However, the role of early non-fibrillar TTR aggregates remains unexplored. We used the EPO producing Hep3B human hepatoma cell line to study the effect of TTR oligomeric aggregates on EPO expression. Hep3B cells were incubated with soluble and oligomeric TTR V30M, and cell proliferation as well as caspase 3/7 activation was evaluated. Relative quantification of EPO mRNA transcripts was performed by real-time PCR. Significant reductions in cell viability (13 ± 7.3%) and activation of caspases 3/7 were seen after 24 h in the presence of oligomeric TTR V30M. Also, EPO expression was significantly reduced (50 ± 2.8%), in normoxic conditions. A reporter assay was constructed with a PCR fragment of the EPO promoter linked to the luciferase gene to evaluate the role of transcription factors targeting the promoter. A significant reduction of EPO promoter activity (53 ± 6.5%) was observed in transfected cells exposed to TTR oligomers. Our results show that oligomeric TTR V30M reduces EPO expression, at least in part through inhibition of promoter activity.