To describe the clinical and molecular characteristics of patients with childhood-onset Stargardt disease (STGD).
Retrospective case series.
Forty-two patients who were diagnosed with STGD in ...childhood at a single institution between January 2001 and January 2012.
A detailed history and a comprehensive ophthalmic examination were undertaken, including color fundus photography, autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), and pattern and full-field electroretinograms. The entire coding region and splice sites of ABCA4 were screened using a next-generation, sequencing-based strategy. The molecular genetic findings of childhood-onset STGD patients were compared with those of adult-onset patients.
Clinical, imaging, electrophysiologic, and molecular genetic findings.
The median ages of onset and the median age at baseline examination were 8.5 (range, 3–16) and 12.0 years (range, 7-16), respectively. The median baseline logarithm of the minimum angle of resolution visual acuity was 0.74. At baseline, 26 of 39 patients (67%) with available photographs had macular atrophy with macular/peripheral flecks; 11 (28%) had macular atrophy without flecks; 1 (2.5%) had numerous flecks without macular atrophy; and 1 (2.5%) had a normal fundus appearance. Flecks were not identified at baseline in 12 patients (31%). SD-OCT detected foveal outer retinal disruption in all 21 patients with available images. Electrophysiologic assessment demonstrated retinal dysfunction confined to the macula in 9 patients (36%), macular and generalized cone dysfunction in 1 subject (4%), and macular and generalized cone and rod dysfunction in 15 individuals (60%). At least 1 disease-causing ABCA4 variant was identified in 38 patients (90%), including 13 novel variants; ≥2 variants were identified in 34 patients (81%). Patients with childhood-onset STGD more frequently harbored 2 deleterious variants (18% vs 5%) compared with patients with adult-onset STGD.
Childhood-onset STGD is associated with severe visual loss, early morphologic changes, and often generalized retinal dysfunction, despite often having less severe fundus abnormalities on examination. One third of children do not have flecks at presentation. The relatively high proportion of deleterious ABCA4 variants supports the hypothesis that earlier onset disease is often owing to more severe variants in ABCA4 than those found in adult-onset disease.
Despite the global pandemic of myopia, the precise molecular mechanism of the onset of myopia remains largely unknown. This is partially because of the lack of efficient murine myopic models that ...allow genetic manipulation at low cost. Here we report a highly practical and reproducible lens-induced myopia model by specially designed frames and lenses for mice. A lens power dependent myopic induction in mice was shown until minus 30 diopter lenses. The phenotype was significantly stronger than form-deprivation myopia. We presented the protocol for precise evaluations of the state of myopia, including refraction, corneal curvature and axial length using up-to-date devices. We also found that myopic mouse eyes showed decreased visual acuity on optokinetic response examination. Finally, we confirmed the anti-myopic effect of 1% atropine using this model, which showed its potential in drug screening. The strong phenotype, stable evaluation and the potential for gene manipulation utilizing the presented method in mice will accelerate the translational research of myopia.
Purpose To investigate tear function and prevalence of dry eye disease (DED) in visual display terminal (VDT) users. Design Cross-sectional study. Methods Six hundred and seventy-two young and ...middle-aged Japanese office workers who used VDT completed questionnaires and underwent dry eye testing. We estimated the prevalence of DED using logistic regression analysis to examine associations between DED and possible risk factors. The ocular surface feature, prevalence of DED, and risk factors were evaluated. Results Of the 672 workers, 561 (83.5%, mean age: 43.3 ± 9.1 years) completed the questionnaire. The percentage of women with a composite outcome of definite DED or probable DED was 76.5%, which was higher than that among men (60.2%; odds ratio OR = 2.00; 95% confidence interval CI, 1.29-3.10, P = .002). Workers over 30 years of age had a higher risk of DED (OR = 2.22; 95% CI, 1.06-4.66), as did workers using a VDT >8 hours per day (OR = 1.94; 95% CI, 1.22-3.09). Average Schirmer value was 18.7 ± 11.7 mm and tear break-up time (TBUT) was 4.0 ± 2.5 seconds (78.6% of study participants had TBUT ≤5 seconds). Conclusions DED is prevalent among young to middle-aged Japanese VDT users. Ophthalmic findings revealed short TBUT and corneal staining accompanied by normal Schirmer test values. Increased risk for DED was noted for women aged over 30 years and prolonged VDT use. Measures to modify the adverse impact of VDT use on the ocular surface may provide a positive impact on public health and quality of life for office workers using VDTs.
IgG4-related disease (IgG4RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. IgG4RD may be ...present in a certain proportion of patients with a wide variety of diseases, including Mikulicz’s disease, autoimmune pancreatitis, hypophysitis, Riedel thyroiditis, interstitial pneumonitis, interstitial nephritis, prostatitis, lymphadenopathy, retroperitoneal fibrosis, inflammatory aortic aneurysm, and inflammatory pseudotumor. Although IgG4RD forms a distinct, clinically independent disease category and is attracting strong attention as a new clinical entity, many questions and problems still remain to be elucidated, including its pathogenesis, the establishment of diagnostic criteria, and the role of IgG4. Here we describe the concept of IgG4RD and up-to-date information on this emerging disease entity.
Lipid metabolism-related gene mutations can cause retinitis pigmentosa, a currently untreatable blinding disease resulting from progressive neurodegeneration of the retina. Here, we demonstrated the ...influence of adiponectin receptor 1 (ADIPOR1) deficiency in retinal neurodegeneration using Adipor1 knockout (KO) mice. Adipor1 mRNA was observed to be expressed in photoreceptors, predominately within the photoreceptor inner segment (PIS), and increased after birth during the development of the photoreceptor outer segments (POSs) where photons are received by the visual pigment, rhodopsin. At 3 weeks of age, visual function impairment, specifically photoreceptor dysfunction, as recorded by electroretinography (ERG), was evident in homozygous, but not heterozygous, Adipor1 KO mice. However, although photoreceptor loss was evident at 3 weeks of age and progressed until 10 weeks, the level of visual dysfunction was already substantial by 3 weeks, after which it was retained until 10 weeks of age. The rhodopsin mRNA levels had already decreased at 3 weeks, suggesting that reduced rhodopsin may have contributed to early visual loss. Moreover, inflammation and oxidative stress were induced in homozygous KO retinas. Prior to observation of photoreceptor loss via optical microscopy, electron microscopy revealed that POSs were present; however, they were misaligned and their lipid composition, including docosahexaenoic acid (DHA), which is critical in forming POSs, was impaired in the retina. Importantly, the expression of Elovl2, an elongase of very long chain fatty acids expressed in the PIS, was significantly reduced, and lipogenic genes, which are induced under conditions of reduced endogenous DHA synthesis, were increased in homozygous KO mice. The causal relationship between ADIPOR1 deficiency and Elovl2 repression, together with upregulation of lipogenic genes, was confirmed in vitro. Therefore, ADIPOR1 in the retina appears to be indispensable for ELOVL2 induction, which is likely required to supply sufficient DHA for appropriate photoreceptor function and survival.
To investigate refractive stability and characterize corneal incision repair up to 3 months after implantation of a new hydrophobic acrylic intraocular lens (IOL) with hydroxyethylmethacrylate using ...a new automated IOL delivery system. This prospective case series included 50 eyes of 50 patients undergoing phacoemulsification and implantation of the Clareon.sup.® CNA0T0 IOL using the AutonoMe.sup.® automated delivery system in the Department of Ophthalmology, Keio University School of Medicine. The clinical data were collected from 46 eyes of 46 patients preoperatively and 1 day, 1 week, and 1 and 3 months postoperatively. Endothelial-side incision gaping, posterior incision retraction, and Descemet's membrane detachment were recorded as present or absent using anterior-segment optical coherence tomography postoperatively. The uncorrected distance and corrected distance visual acuities improved and stabilized 1 week postoperatively. The anterior chamber depth was stable from 1 week postoperatively. The subjective refraction was stable from 1 day postoperatively. Descemet's membrane detachments and endothelial-side wound gaping were seen in 19 (41.3%) eyes and 34 (73.9%) eyes 1 day postoperatively and decreased gradually. Posterior incision retraction was seen in eight eyes (17.4%) on day 1 and increased to 19 eyes (41.3%) 3 months postoperatively. The Clareon IOL had excellent refractive stability from day 1 postoperatively. The AutonoMe automated delivery system enables safe IOL implantation through a 2.4-mm corneal incision, although the wound required longer than 1 month to heal postoperatively.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate the morphologic changes in the corneal subbasal nerve (CSN) plexus in wild-type (WT) mice after exposure to scopolamine-induced dry eye stress (DES) by using in vivo confocal microscopy.
...Twenty right eyes of twenty (n = 20) 8-week-old WT BALB/c male mice were investigated. The mice were divided into two experimental groups; 10 eyes of 10 mice exposed to DES for 28 days and 10 eyes of 10 mice were used as a control group. All mice underwent examinations for aqueous tear secretion quantity, tear film breakup time (TBUT), corneal vital staining. and corneal sensitivity thrice (pre-experiment, 2nd week, and 4th week). CSN density, tortuosity, reflectivity, and dendritic cell (DC) densities were examined.
The mean aqueous tear secretion (P < 0.0001) and TBUTs (P < 0.0001) were significantly decreased after DES. The mean corneal vital staining scores were significantly higher (fluorescein, P < 0.0001; lissamine, P < 0.0001), the mean TBUTs were significantly shorter (P < 0.0001), and the corneal sensitivities (P < 0.0001) were significantly lower in the dry eye-induced mice than the control mice. The mean CSN fiber density (P < 0.0001) and the reflectivity (P < 0.001) were significantly lower; the mean tortuosity and the mean DC density were significantly higher (P < 0.0001) in the dry eye mice.
Our data demonstrated that prolonged exposure to DES resulted in alterations of CSN density; DC intensity, reflectivity, and tortuosity as well as in tear volume; TBUT; fluorescein and lissamine green staining scores; and the corneal sensitivity in WT mice.
This study compared the axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), mean anterior corneal radius of curvature (Rm), and postoperative ...refractive outcomes obtained from two different swept-source optical coherence biometers, the ARGOS (Movu, Nagoya, Japan), which uses the segmental refractive index for each segment, and the IOLMaster 700 (Carl Zeiss Meditec, Jena, Germany), which uses an equivalent refractive index for the entire eye. One hundred and six eyes of 106 patients with cataracts were included. The refractive outcomes using the Barrett Universal II, Haigis, Hoffer Q, and SRK/T formulas were evaluated. The mean AL, CCT, ACD, and Rm differed significantly (P < 0.001) with the IOLMaster 700 (25.22 mm, 559 µm, 3.23 mm, and 7.69 mm) compared with the ARGOS (25.14 mm, 533 µm, 3.33 mm, and 7.66 mm). The mean LTs did not differ significantly. The percentages of eyes within ±0.50 and ±1.00 diopter of the predicted refraction did not differ significantly (P > 0.05). The accuracy of the intraocular lens power calculations was clinically acceptable with both biometers, although the ocular biometry using these two biometers exhibited certain differences.
Tear fluid secreted from the exocrine lacrimal gland (LG) has an essential role in maintaining a homeostatic environment for a healthy ocular surface. Tear secretion is regulated by the sympathetic ...and parasympathetic components of the autonomic nervous system, although the contribution of each component is not fully understood. To investigate LG innervation, we identified sympathetic and parasympathetic postganglionic nerves, specifically innervating the mouse LG, by injecting a retrograde neuronal tracer into the LG. Interruption of neural stimuli to the LG by the denervation of these postganglionic nerves immediately and chronically decreased tear secretion, leading to LG atrophy along with destruction of the lobular structure. This investigation also found that parasympathetic, but not sympathetic, innervation was involved in these alterations.
Diabetic retinopathy (DR) is one of the leading causes of blindness globally. Retinal neuronal abnormalities occur in the early stage in DR. Therefore, maintaining retinal neuronal activity in DR may ...prevent vision loss. Previously, pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, was suggested as a promising drug in hypertriglyceridemia. However, the role of pemafibrate remains obscure in DR. Therefore, we aimed to unravel systemic and retinal changes by pemafibrate in diabetes. Adult mice were intraperitoneally injected with streptozotocin (STZ) to induce diabetes. After STZ injection, diet supplemented with pemafibrate was given to STZ-induced diabetic mice for 12 weeks. During the experiment period, body weight and blood glucose levels were examined. Electroretinography was performed to check the retinal neural function. After sacrifice, the retina, liver, and blood samples were subjected to molecular analyses. We found pemafibrate mildly improved blood glucose level as well as lipid metabolism, boosted liver function, increased serum fibroblast growth factor21 level, restored retinal functional deficits, and increased retinal synaptophysin protein expression in STZ-induced diabetic mice. Our present data suggest a promising pemafibrate therapy for the prevention of early DR by improving systemic metabolism and protecting retinal function.
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