BACKGROUND: Biallelic ZBTB11 variants have previously been associated with an ultrarare subtype of autosomal recessive intellectual developmental disorder (MRT69).
OBJECTIVE: The aim was to provide insights into the clinical and genetic characteristics of ZBTB11-related disorders (ZBTB11-RD), with a particular emphasis on progressive complex movement abnormalities.
METHODS: Thirteen new and 16 previously reported affected individuals, ranging in age from 2 to 50 years, with biallelic ZBTB11 variants underwent clinical and genetic characterization.
RESULTS: All patients exhibited a range of neurodevelopmental phenotypes with varying severity, encompassing ocular and neurological features. Eleven new patients presented with complex abnormal movements, including ataxia, dystonia, myoclonus, stereotypies, and tremor, and 7 new patients exhibited cataracts. Deep brain stimulation was successful in treating 1 patient with generalized progressive dystonia. Our analysis revealed 13 novel variants.
CONCLUSIONS: This study provides additional insights into the clinical features and spectrum of ZBTB11-RD, highlighting the progressive nature of movement abnormalities in the background of neurodevelopmental phenotype. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Depression has been shown to be associated with eye diseases, including dry eye disease (DED), cataracts, glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). This narrative review explores potential pathophysiological connections between depression and eye disease, as well as its potential correlations with ocular parameters. Methods: A literature search was conducted in August 2022 in PUBMED, EMBASE, and PsycINFO. Published articles related to the subject were consolidated and classified according to respective eye diseases and pathophysiological mechanisms. Results: The literature reviewed suggests that common pathophysiological states like inflammation and neurodegeneration may contribute to both depression and certain eye diseases, while somatic symptoms and altered physiology, such as disruptions in circadian rhythm due to eye diseases, can also influence patients\' mood states. Grounded in the shared embryological, anatomical, and physiological features between the eye and the brain, depression is also correlated to changes observed in non-invasive ophthalmological imaging modalities, such as changes in the retinal nerve fibre layer and retinal microvasculature. Conclusions: There is substantial evidence of a close association between depression and eye diseases. Understanding the underlying concepts can inform further research on treatment options and monitoring of depression based on ocular parameters.

UNASSIGNED: Shear wave elastography (SWE) is a novel imaging technique that provides quantitative assessments of tissue stiffness. This non-invasive method offers real-time, quantitative measurements and has been widely applied to various tissues, providing valuable diagnostic insights.
UNASSIGNED: This study aimed to investigate the feasibility of using SWE to evaluate the stiffness of the lens in patients with age-related cataracts.
UNASSIGNED: A comparative analysis involving 92 patients diagnosed with age-related cataracts and 39 healthy controls was conducted. Lens stiffness was quantified using SWE measurements. The lens nucleus of all participants was graded based on the Lens Opacities Classification System II (LOCS II). Correlations between the stiffness of the lens and age were also analyzed.
UNASSIGNED: The study indicates that both the stiffness of the lens and the lens nucleus were significantly higher in patients with age-related cataracts compared to healthy controls (P < 0.001). In patients with age-related cataracts, although lens nucleus stiffness variations across different grades of cataract severity were not statistically significant, all grades displayed increased stiffness relative to healthy controls. Additionally, a significant positive correlation between lens stiffness and age was observed in all participants (P < 0.001).
UNASSIGNED: SWE appears to be a promising imaging technique for quantitatively assessing the mechanical characteristics of the lens in patients with age-related cataracts.

UNASSIGNED: To determine the genetic causes of monogenic inherited diseases in a couple using clinical whole exome sequencing (WES) and advise on their reproductive choices.
UNASSIGNED: WES was applied to a couple seeking reproductive advice, the female with short stature and the male with congenital cataracts.
UNASSIGNED: (1) The woman exhibited a 13.8 Kb heterozygous deletion at chrX: 591590-605428 (hg19). This region corresponds to exons 2-6 of the short-stature homeobox-containing (SHOX) gene (NM000451). Associated diseases involving the SHOX gene range from severe Leri-Weill dyschondrosteosis to mild nonspecific short stature. Meanwhile, further validation using a quantitative reverse transcription polymerase chain reaction assay confirmed the heterozygous deletion of the SHOX gene in the proband, as well as other family members with similar clinical characteristics (the proband\'s mother, aunt, and cousin). Multiple pathogenic reports of this variant have been included in the HGMD database. Per the American College of Medical Genetics and Genomics (ACMG) classification criteria, this deletion is classified as pathogenic. (2) For the male patient, a heterozygous variant was detected in the CRYBB3 gene: NM004076: c.226G>A (p.Gly76R). Variants in the CRYBB3 gene can cause Cataract 22 (OMIM: 609741). At present, this variant locus is not included in databases such as the gnomAD, while both SIFT and PolyPhen2 deem this locus \'damaging\'. Moreover, further validation by Sanger sequencing confirmed that the variant was inherited from the male patient\'s mother, who also had cataracts. According to ACMG standards and guidelines, the c.226G>A (p.Gly76Arg) variant in the CRYBB3 gene is classified as having \'uncertain significance\'.
UNASSIGNED: WES identified pathogenic variants in both individuals, suggesting a 25% chance of a healthy child naturally. Third-generation assisted reproductive techniques are recommended to minimize the risk of affected offspring.

This study assessed the prevalence of myopia, cataracts, glaucoma, and macular degeneration among Koreans over 40, utilizing data from the 7th Korea National Health and Nutrition Examination Survey (KNHANES VII, 2018). We analyzed 204,973 adults (44% men, 56% women; mean age 58.70 ± 10.75 years), exploring the association between myopia and these eye diseases through multivariate logistic regression, adjusting for confounders and calculating adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results showed a myopia prevalence of 44.6%, cataracts at 19.4%, macular degeneration at 16.2%, and glaucoma at 2.3%, with significant differences across ages and genders. A potential link was found between myopia and an increased risk of cataracts and macular degeneration, but not with glaucoma. Additionally, a higher dietary intake of carbohydrates, polyunsaturated and n-6 fatty acids, vitamins, and minerals correlated with lower risks of these diseases, underscoring the importance of the diet in managing and preventing age-related eye conditions. These findings highlight the need for dietary considerations in public health strategies and confirm myopia as a significant risk factor for specific eye diseases in the aging Korean population.

OBJECTIVE: Although I-131 is relatively safe, there is limited focus on probable eye-related side effects after radioactive iodine (RAI) therapy. Thus, we aimed to provide evidence for the adverse outcomes of I-131, exclusively in patients with thyroid cancer.
METHODS: A systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was designed to examine the ocular complications of RAI therapy. Databases including PubMed, Scopus, and Web of Science were searched until October 2023 with specific thyroid neoplasms, ophthalmology and iodine terms. After thorough screening and review, relevant data were extracted.
RESULTS: The database search yielded 3434 articles, which resulted in the final 28 eligible studies. These studies investigated ophthalmic symptoms following RAI therapy, classifying them as obstructive diseases (for example, nasolacrimal duct obstruction; median incidence rate: 6.8%), inflammatory symptoms (median incidence rate: 13%), and cataracts (median incidence rate: 2.5 and 5%). The most common time interval between RAI therapy and the onset of symptoms was within the first 12 months and then declined in the preceding years. A strong positive correlation was observed between higher I-131 doses of more than 100 to 150 mCi (3.7-5.55 GBq) and the risk of symptom development. Ages older than 45 also showed a significant association with nasolacrimal duct obstruction.
CONCLUSIONS: The risk of ophthalmic complications is associated with various factors, including the administration of high I-131 doses, age of more than 45 years, and time to event within the first 12 months. Considering these conditions may help enhance patient care and prevent adverse outcomes that may limit patients\' quality of life.

Cataracts are one of the leading causes of blindness, with an estimated 95 million people affected worldwide. A hallmark of cataract development is lens opacification, typically associated not only with aging but also radiation exposure as encountered by interventional radiologists and astronauts during the long-term space mission. To better understand radiation-induced cataracts, the adverse outcome pathway (AOP) framework was used to structure and evaluate knowledge across biological levels of organization (e.g., macromolecular, cell, tissue, organ, organism and population). AOPs identify a sequence of key events (KEs) causally connected by key event relationships (KERs) beginning with a molecular initiating event to an adverse outcome (AO) of relevance to regulatory decision-making. To construct the cataract AO and retrieve evidence to support it, a scoping review methodology was used to filter, screen, and review studies based on the modified Bradford Hill criteria. Eight KEs were identified that were moderately supported by empirical evidence (e.g., dose-, time-, incidence-concordance) across the adjacent (directly linked) relationships using well-established endpoints. Over half of the evidence to justify the KER linkages was derived from the evidence stream of biological plausibility. Early KEs of oxidative stress and protein modifications had strong linkages to downstream KEs and could be the focus of countermeasure development. Several identified knowledge gaps and inconsistencies related to the quantitative understanding of KERs which could be the basis of future research, most notably directed to experiments in the range of low or moderate doses and dose-rates, relevant to radiation workers and other occupational exposures.

Duchenne muscular dystrophy (DMD) is an X-linked disorder due to a dystrophin mutation and is the leading cause of muscular dystrophy. DMD presents with characteristic systemic effects, including severe muscular atrophy, cardiomyopathy, and ocular manifestations. Performing corneal refractive surgeries in patients with DMD raises concerns regarding patient positioning, risk of cataracts, and other comorbid conditions. Published reports of photorefractive keratectomy, laser-assisted in situ keratomileuses, and small incision lenticule extraction are lacking in this population. Here, we discuss a patient being evaluated for a corneal refractive surgery. This article also discusses the current understanding of DMD, known ocular manifestations, and factors to consider when evaluating a patient for potential corrective vision laser surgery.

UNASSIGNED: Degenerate eye disorders, such as glaucoma, cataracts and age-related macular degeneration (AMD), are prevalent causes of blindness and visual impairment worldwide. Other eye disorders, including limbal stem cell deficiency (LSCD), dry eye diseases (DED), and retinitis pigmentosa (RP), result in symptoms such as ocular discomfort and impaired visual function, significantly impacting quality of life. Traditional therapies are limited, primarily focus on delaying disease progression, while emerging stem cell therapy directly targets ocular tissues, aiming to restore ocular function by reconstructing ocular tissue.
UNASSIGNED: The utilization of stem cells for the treatment of diverse degenerative ocular diseases is becoming increasingly significant, owing to the regenerative and malleable properties of stem cells and their functional cells. Currently, stem cell therapy for ophthalmopathy involves various cell types, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and retinal progenitor cells (RPCs). In the current article, we will review the current progress regarding the utilization of stem cells for the regeneration of ocular tissue covering key eye tissues from the cornea to the retina. These therapies aim to address the loss of functional cells, restore damaged ocular tissue and or in a paracrine-mediated manner. We also provide an overview of the ocular disorders that stem cell therapy is targeting, as well as the difficulties and opportunities in this field.
UNASSIGNED: Stem cells can not only promote tissue regeneration but also release exosomes to mitigate inflammation and provide neuroprotection, making stem cell therapy emerge as a promising approach for treating a wide range of eye disorders through multiple mechanisms.

Previous studies have reported that patients with retinitis pigmentosa (RP) may develop open-angle and angle-closure glaucoma. We conducted a chart review of patients with RP. Two siblings with RP associated with a mutation in the PDE6B gene (c. 1540del, p.Leu514Trpfs*61) developed cystoid macular edema (CME) as part of the disease. For this reason, they both underwent intravitreal steroid injections. Both brothers developed steroid-induced glaucoma (SIG). Despite undergoing maximal medical therapy, they underwent seton implants to control their intraocular pressure. A third female patient with RP due to a mutation in the RPGR gene underwent cataract surgery. Topical steroids were prescribed and developed SIG. Increased intraocular pressure remains a complication of topical, injected, and systemic steroids. However, steroids may be needed to treat post-operatively and patients with CME. This case series unveils a complex association between RP and key comorbidities in these patients, with a focus on cataracts, glaucoma, and macular edema. Cataract surgery in patients with RP shows a link to the emergence of glaucoma, particularly in those with RPGR and PDE6B gene mutations, revealing a novel association with PDE6B mutations not previously documented. Furthermore, the paper explores a unique parallel with Schwartz-Matsuo syndrome, suggesting that patients with RP undergoing cataract surgery may develop increased intraocular pressure due to an outflow disturbance akin to Schwartz syndrome. This novel perspective deepens our understanding of the pathophysiological mechanisms governing intraocular pressure dynamics in patients with RP. To our knowledge, this is the first report of steroid-induced glaucoma in patients with RP due to mutations in the PDE6B gene. Intraocular pressure evaluation remains of utmost importance in the follow-up of patients with the disease.