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JAMA Network Open Jan 2021Survivors of Ebola virus disease (EVD) may experience ocular sequelae. Comparison with antibody-negative individuals from the local population is required to...
IMPORTANCE
Survivors of Ebola virus disease (EVD) may experience ocular sequelae. Comparison with antibody-negative individuals from the local population is required to characterize the disease.
OBJECTIVE
To assess features of ophthalmic disease specific to EVD.
DESIGN, SETTING, AND PARTICIPANTS
This baseline cross-sectional analysis of survivors of EVD and their close contacts was conducted within PREVAIL III, a 5-year, longitudinal cohort study. Participants who enrolled at John F. Kennedy Medical Center in Liberia, West Africa from June 2015 to March 2016 were included in this analysis. Close contacts were defined as household members or sex partners of survivors of EVD. Data were analyzed from July 2016 to July 2020.
EXPOSURES
All participants, both survivors and close contacts, underwent testing of IgG antibody levels against Ebola virus surface glycoprotein.
MAIN OUTCOMES AND MEASURES
Ocular symptoms, anterior and posterior ophthalmologic examination findings, and optical coherence tomography images were compared between antibody-positive survivors and antibody-negative close contacts.
RESULTS
A total of 564 antibody-positive survivors (320 [56.7%] female; mean [SD] age, 30.3 [14.0] years) and 635 antibody-negative close contacts (347 [54.6%] female; mean [SD] age, 25.8 [15.5] years) were enrolled in this study. Survivors were more likely to demonstrate color vision deficit (28.9% vs 19.0%, odds ratio [OR], 1.6; 95% CI, 1.2-2.1) and lower intraocular pressure (12.4 vs 13.5 mm Hg; mean difference, -1.2 mm Hg; 95% CI, -1.6 to -0.8 mm Hg) compared with close contacts. Dilated fundus examination revealed a higher percentage of vitreous cells (7.8% vs 0.5%; OR, 16.6; 95% CI, 5.0-55.2) and macular scars (4.6% vs 1.6%; OR, 2.8; 95% CI, 1.4-5.5) in survivors than in close contacts. Uveitis was present in 26.4% of survivors and 12.1% of close contacts (OR, 2.4; 95% CI, 1.8-3.2). Among all participants with uveitis, survivors were more likely than close contacts to have intermediate uveitis (34.2% vs 6.5% of all cases; OR, 7.8; 95% CI, 3.1-19.7) and had thicker mean central subfield thickness on optical coherence tomography (222 vs 212 μm; mean difference, 14.4 μm; 95% CI, 1.9-26.9 μm).
CONCLUSIONS AND RELEVANCE
In this cross-sectional study, survivors of EVD had a distinct spectrum of ocular and neuro-ophthalmologic findings compared with close contacts that potentially require medical and surgical treatment.
Topics: Adult; Cicatrix; Color Vision Defects; Cross-Sectional Studies; Eye Diseases; Female; Hemorrhagic Fever, Ebola; Humans; Intraocular Pressure; Liberia; Longitudinal Studies; Macular Edema; Male; Survivors; Tomography, Optical Coherence; Uveitis
PubMed: 33399856
DOI: 10.1001/jamanetworkopen.2020.32216 -
European Journal of Ophthalmology Nov 2023Achromatopsia is an autosomal recessive cone dysfunction syndrome, characterized by absence of color discrimination, low visual acuity, photophobia, and nystagmus....
BACKGROUND
Achromatopsia is an autosomal recessive cone dysfunction syndrome, characterized by absence of color discrimination, low visual acuity, photophobia, and nystagmus. Achromatopsia constitutes a common cause of visual impairment in children, with a prevalence of 1:30,000 worldwide.
OBJECTIVE
To characterize the clinical characteristics of achromatopsia, the main genes causing the disease in our population and the clinical course of the disease, with an emphasis on visual function stability with increasing age.
METHODS
Retrospective study based on medical charts of patients with achromatopsia. Patients were divided into two groups according to their age at last follow-up: older and younger than 10 years. A subset of patients with long term follow-up were analyzed separately, with patients being described in both age groups.
RESULTS
Seventy-six patients were included in the study. The mean age was 14.28 years. Variants in the CNGA3 gene were the most common (73.6%). Clinical characteristics included photophobia (96.2%), nystagmus (93.6%), hypermetropia (72.3%) and strabismus (51.1%). In the large cohort there was no correlation of age with visual acuity ( = 0.129). In the separate subset cohort with long follow-up there was a relative improvement in visual acuity with age ( < 0.001).
CONCLUSIONS
CNGA3 is the main gene associated with achromatopsia in our population (around ∼ 73%), which is in contrast to the distribution worldwide (∼ 25%). Most achromats suffer from photophobia and nystagmus, and the main refractive error is hypermetropia. Achromatopsia's natural course seems to be stationary, and there may even be a slight improvement in visual acuity with time.
PubMed: 37920903
DOI: 10.1177/11206721231212768 -
Current Biology : CB Apr 2023Most defects causing retinal degeneration in retinitis pigmentosa (RP) are rod-specific mutations, but the subsequent degeneration of cones, which produces loss of...
Most defects causing retinal degeneration in retinitis pigmentosa (RP) are rod-specific mutations, but the subsequent degeneration of cones, which produces loss of daylight vision and high-acuity perception, is the most debilitating feature of the disease. To understand better why cones degenerate and how cone vision might be restored, we have made the first single-cell recordings of light responses from degenerating cones and retinal interneurons after most rods have died and cones have lost their outer-segment disk membranes and synaptic pedicles. We show that degenerating cones have functional cyclic-nucleotide-gated channels and can continue to give light responses, apparently produced by opsin localized either to small areas of organized membrane near the ciliary axoneme or distributed throughout the inner segment. Light responses of second-order horizontal and bipolar cells are less sensitive but otherwise resemble those of normal retina. Furthermore, retinal output as reflected in responses of ganglion cells is less sensitive but maintains spatiotemporal receptive fields at cone-mediated light levels. Together, these findings show that cones and their retinal pathways can remain functional even as degeneration is progressing, an encouraging result for future research aimed at enhancing the light sensitivity of residual cones to restore vision in patients with genetically inherited retinal degeneration.
Topics: Humans; Retinal Degeneration; Retinal Cone Photoreceptor Cells; Retina; Retinitis Pigmentosa; Color Vision
PubMed: 36977418
DOI: 10.1016/j.cub.2023.03.007 -
Advances in Experimental Medicine and... 2023Throughout the last 25 years, exceptional progress in retinal gene therapy was achieved. The major breakthrough was realized in 2017 when the FDA approved the...
Throughout the last 25 years, exceptional progress in retinal gene therapy was achieved. The major breakthrough was realized in 2017 when the FDA approved the adeno-associated virus (AAV)-based gene therapy for treatment of the monogenetic disorder Leber congenital amaurosis type 2 (LCA2). Since then, many therapies for inherited retinal diseases (IRD) reached phase I/II clinical trials, targeting diseases like achromatopsia, choroideremia, retinitis pigmentosa, Stargardt disease, and many more (reviewed in (Trapani and Auricchio, Trends Mol Med 24:669-681, 2018)). Advanced vector and capsid design technologies as well as improved gene transfer and gene editing methods may lead to refined therapies for various eye diseases. Many research departments worldwide focus on optimizing transgene expression by designing novel AAV serotypes. Besides serotype tropism, the method of injection (intravitreal, subretinal, or suprachoroidal) (Han et al., Hum Gene Ther 31:1288-1299, 2020) defines the efficiency outcome along with the use of tissue-specific promotors which play a critical role for cell targeting.
Topics: Serogroup; Dependovirus; Transduction, Genetic; Retina; Genetic Therapy; Genetic Vectors
PubMed: 37440025
DOI: 10.1007/978-3-031-27681-1_20 -
International Ophthalmology Mar 2020As proven in studies dating back to the eighteenth century, color vision changes may occur early in the course of glaucoma. Our aim was to reevaluate the incidence of...
PURPOSE
As proven in studies dating back to the eighteenth century, color vision changes may occur early in the course of glaucoma. Our aim was to reevaluate the incidence of acquired color vision deficiency in glaucoma patients of the University hospital Zürich by using the Panel D-15 test.
METHODS
Inclusion criteria of the study involved a diagnosis of glaucoma, age equal or greater than 18 years with no upper limit and a best-corrected visual acuity (BCVA) smaller than ≤ 0.7 logMAR. All volunteers were tested twice monocularly for color vision with (1) the Ishihara color plate test and (2) the Farnsworth and Lanthony Panel D-15 test by one examiner (L.B.). Using the Moment of Inertia Method of Vingrys and King-Smith (Investig Ophthalmol Vis Sci 29(1):50-63, 1988), we measured the color defect type (blue-yellow, red-green or non-selective).
RESULTS
One hundred and fifty-one eyes of 87 glaucoma patients were included in this study. Nine eyes showed a deficient result in the Ishihara test, which proves a congenital red-green weakness. Fifty-one (33.8%) eyes showed color vision anomalies in the desaturated test and 24 (15.9%) eyes in the saturated Panel D-15 test. A total of 25.2% and 8.6% of eyes in the desaturated and saturated test were diffuse dyschromatopsia, respectively. The second most prevalent deficiencies were blue-yellow defects with 4.0% and 4.6% of saturated and desaturated results. Just the covariate visual acuity had a significant influence on the Panel D-15 result, whereas other variables like age, sex or intraocular pressure did not show any impact.
CONCLUSION
This study ascertains that the long-known theory of color vision defects in patients with glaucoma is also relevant in our sample of 151 eyes, providing continuity to claims firstly reported many years ago. Despite our results highlighting more diffuse dyschromatopsia than other similar experiments, we have also proven that the tritanomalous defects occur more frequently than other color defects.
Topics: Adult; Aged; Aged, 80 and over; Color Perception Tests; Color Vision; Color Vision Defects; Female; Glaucoma; Humans; Incidence; Intraocular Pressure; Male; Middle Aged; Switzerland; Visual Acuity
PubMed: 31705359
DOI: 10.1007/s10792-019-01218-1 -
Ophthalmology Oct 2023
Topics: Humans; Color Vision Defects; Macula Lutea; Electroretinography; Cyclic Nucleotide-Gated Cation Channels
PubMed: 36682978
DOI: 10.1016/j.ophtha.2022.11.001 -
Ophthalmology Dec 2023To describe the largest, most phenotypically and genetically diverse cohort of patients with inherited retinal disease (IRD)-related Coats-like vasculopathy (CLV).
PURPOSE
To describe the largest, most phenotypically and genetically diverse cohort of patients with inherited retinal disease (IRD)-related Coats-like vasculopathy (CLV).
DESIGN
Multicenter retrospective cohort study.
PARTICIPANTS
A total of 67 patients with IRD-related CLV.
METHODS
Review of clinical notes, ophthalmic imaging, and molecular diagnosis from 2 international centers.
MAIN OUTCOME MEASURES
Visual function, retinal imaging, management, and response to treatment were evaluated and correlated.
RESULTS
The prevalence of IRD-related CLV was 0.5%; 54% of patients had isolated retinitis pigmentosa (RP), 21% had early-onset severe retinal dystrophy, and less frequent presentations were syndromic RP, sector RP, cone-rod dystrophy, achromatopsia, PAX6-related dystrophy, and X-linked retinoschisis. The overall age of patients at CLV diagnosis was 30.7 ± 16.9 years (1-83). Twenty-one patients (31%) had unilateral CLV, and the most common retinal features were telangiectasia, exudates, and exudative retinal detachment (ERD) affecting the inferior and temporal retina. Macular edema/schisis was observed in 26% of the eyes, and ERD was observed in 63% of the eyes. Fifty-four patients (81%) had genetic testing, 40 of whom were molecularly solved. Sixty-six eyes (58%) were observed, 17 eyes (15%) were treated with a single modality, and 30 eyes (27%) had a combined approach. Thirty-five eyes (31%) were "good responders," 42 eyes (37%) were "poor responders," 22 eyes (19%) had low vision at baseline and were only observed, and 12 eyes (11%) did not have longitudinal assessment. Twenty-one observed eyes (62%) responded well versus 14 (33%) treated eyes. Final best-corrected visual acuity was significantly worse than baseline (P = 0.002); 40 patients (60%) lost 15 ETDRS letters or more over follow-up in 1 or both eyes, and 21 patients (31%) progressed to more advanced stages of visual impairment.
CONCLUSIONS
Inherited retinal disease-related CLV is rare, sporadic, and mostly bilateral; there is no gender predominance, and it can occur in diverse types of IRD at any point of the disease, with a mean onset in the fourth decade of life. Patients with IRD-related CLV who have decreased initial visual acuity, ERD, CLV changes affecting 2 or more retinal quadrants, and CRB1-retinopathy may be at higher risk of a poor prognosis.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Prevalence; Retrospective Studies; Retina; Retinal Detachment; Retinal Dystrophies; Retinitis Pigmentosa; Cone-Rod Dystrophies; Vision, Low; Eye Proteins; Membrane Proteins; Nerve Tissue Proteins
PubMed: 37544434
DOI: 10.1016/j.ophtha.2023.07.027 -
Genes Feb 2023This multicenter study aimed to characterize Korean patients with achromatopsia. The patients' genotypes and phenotypes were retrospectively evaluated. Twenty-one...
This multicenter study aimed to characterize Korean patients with achromatopsia. The patients' genotypes and phenotypes were retrospectively evaluated. Twenty-one patients (with a mean age at the baseline of 10.9 years) were enrolled and followed up for a mean of 7.3 years. A targeted gene panel or exome sequencing was performed. The pathogenic variants of the four genes and their frequencies were identified. and were equally the most prevalent genes: (N = 8, 38.1%), (N = 8, 38.1%), (N = 3, 14.3%), and (N = 2, 9.5%). The degree of functional and structural defects varied among the patients. The patients' age exhibited no significant correlation with structural defects. During the follow-up, the visual acuity and retinal thickness did not change significantly. In -achromatopsia patients, a proportion of patients with a normal foveal ellipsoid zone on the OCT was significantly higher than that of patients with other causative genes (62.5% vs. 16.7%; = 0.023). In -achromatopsia patients, the same proportion was significantly lower than that of patients with other causative genes (0% vs. 58.3%; = 0.003). Korean patients with achromatopsia showed similar clinical features but a higher prevalence of variants than those of other ethnic groups. The retinal phenotypes of the variants were more likely to be worse than those of other genes.
Topics: Humans; Color Vision Defects; Retrospective Studies; Cyclic Nucleotide-Gated Cation Channels; Republic of Korea
PubMed: 36833446
DOI: 10.3390/genes14020519 -
Frontiers in Neuroscience 2020Parkinson's disease (PD) is characterized by motor dysfunctions including bradykinesia, tremor at rest and motor instability. These symptoms are associated with the... (Review)
Review
Parkinson's disease (PD) is characterized by motor dysfunctions including bradykinesia, tremor at rest and motor instability. These symptoms are associated with the progressive degeneration of dopaminergic neurons originating in the and projecting to the corpus striatum, and by accumulation of cytoplasmic inclusions mainly consisting of aggregated alpha-synuclein, called Lewy bodies. PD is a complex, multifactorial disorder and its pathogenesis involves multiple pathways and mechanisms such as α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport, and neuroinflammation. Motor symptoms manifest when there is already an extensive dopamine denervation. There is therefore an urgent need for early biomarkers to apply disease-modifying therapeutic strategies. Visual defects and retinal abnormalities, including decreased visual acuity, abnormal spatial contrast sensitivity, color vision defects, or deficits in more complex visual tasks are present in the majority of PD patients. They are being considered for early diagnosis together with retinal imaging techniques are being considered as non-invasive biomarkers for PD. Dopaminergic cells can be found in the retina in a subpopulation of amacrine cells; however, the molecular mechanisms leading to visual deficits observed in PD patients are still largely unknown. This review provides a comprehensive analysis of the retinal abnormalities observed in PD patients and animal models and of the molecular mechanisms underlying neurodegeneration in parkinsonian eyes. We will review the role of α-synuclein aggregates in the retina pathology and/or in the onset of visual symptoms in PD suggesting that α-synuclein aggregates are harmful for the retina as well as for the brain. Moreover, we will summarize experimental evidence suggesting that the optic nerve pathology observed in PD resembles that seen in mitochondrial optic neuropathies highlighting the possible involvement of mitochondrial abnormalities in the development of PD visual defects. We finally propose that the eye may be considered as a complementary experimental model to identify possible novel disease' pathways or to test novel therapeutic approaches for PD.
PubMed: 33192254
DOI: 10.3389/fnins.2020.567129 -
International Medical Case Reports... 2023To describe a case of optic neuropathy after prolonged sirolimus therapy in the setting of cardiac transplant.
OBJECTIVE
To describe a case of optic neuropathy after prolonged sirolimus therapy in the setting of cardiac transplant.
BACKGROUND
Sirolimus is an immunosuppressant that inhibits Mechanistic Target of Rapamycin (mTOR) and blocks T-cell activation and B-cell differentiation by preventing response to Interleukin-2 (IL-2). Tacrolimus is another immunosuppressive agent, one of the known but uncommon side effects of which is bilateral optic neuropathy years after taking the medication. To the best of our knowledge, this is the first report of sequential optic neuropathy after years of treatment with sirolimus.
CASE PRESENTATION
A 69-year-old male with a history of cardiac transplantation presented with progressive, sequential, and painless vision loss. Visual acuity was 20/150 OD and 20/80 OS, with impaired color vision in both eyes (Ishihara 0/10) and bilateral disc pallor and mild optic disc edema in the left eye. Visual field was constricted in both eyes. The patient was on prolonged sirolimus therapy for over 7 years. Orbital MRI revealed bilateral chiasmatic thickness and FLAIR hyperintensity, without optic nerve enhancement post gadolinium. After extensive work up, other etiologies such as infectious, inflammatory, and neoplastic lesions were ruled out. Subsequently, sirolimus was substituted with cyclosporin that led to gradual improvement of vision and visual fields bilaterally.
CONCLUSION
Optic neuropathy is a rare side effect of tacrolimus, which has been seen as sudden, painless, and bilateral vision loss in post-transplant patients. Other concurrent medications influencing the cytochrome P4503A enzyme complexes may alter the pharmacokinetics of tacrolimus and increase the likelihood of toxicity. Discontinuation of offending agent has been shown to improve visual defects. We presented a rare case of optic neuropathy in a patient on sirolimus, whose visual defects improved upon discontinuation of sirolimus and switching to cyclosporin.
PubMed: 37284436
DOI: 10.2147/IMCRJ.S388481