-
BMC Ophthalmology Apr 2024The goal of the study was to search for novel bi-allelic CRB1 mutations, and then to analyze the CRB1 literature at the genotypic and phenotypic levels. (Meta-Analysis)
Meta-Analysis
PURPOSE
The goal of the study was to search for novel bi-allelic CRB1 mutations, and then to analyze the CRB1 literature at the genotypic and phenotypic levels.
APPROACH
We screened various variables such as the CRB1 mutation types, domains, exons, and genotypes and their relation with specific ocular phenotypes. An emphasis was given to the bi-allelic missense and nonsense mutations because of their high prevalence compared to other mutation types. Finally, we quantified the effect of various non-modifiable factors over the best-corrected visual acuity oculus uterque (BCVA OU) using multivariate linear regression models and identified genetic interactions.
RESULTS
A novel bi-allelic missense in the exon 9 of CRB1; c.2936G > A; p.(Gly979Asp) was found to be associated with rod-cone dystrophy (RCD). CRB1 mutation type, exons, domains, and genotype distribution varied significantly according to fundus characteristics, such as peripheral pigmentation and condition, optic disc, vessels, macular condition, and pigmentation (P < 0.05). Of the 154 articles retrieved from PubMed, 96 studies with 439 bi-allelic CRB1 patients were included. Missense mutations were significantly associated with an absence of macular pigments, pale optic disc, and periphery pigmentation, resulting in a higher risk of RCD (P < 0.05). In contrast, homozygous nonsense mutations were associated with macular pigments, periphery pigments, and a high risk of LCA (P < 0.05) and increased BCVA OU levels. We found that age, mutation types, and inherited retinal diseases were critical determinants of BCVA OU as they significantly increased it by 33% 26%, and 38%, respectively (P < 0.05). Loss of function alleles additively increased the risk of LCA, with nonsense having a more profound effect than indels. Finally, our analysis showed that p.(Cys948Tyr) and p.(Lys801Ter) and p.(Lys801Ter); p.(Cys896Ter) might interact to modify BCVA OU levels.
CONCLUSION
This meta-analysis updated the literature and identified genotype-phenotype associations in bi-allelic CRB1 patients.
Topics: Humans; Alleles; Codon, Nonsense; Nerve Tissue Proteins; Genetic Association Studies; Retina; Phenotype; Mutation; Eye Proteins; Pedigree; DNA Mutational Analysis; Membrane Proteins
PubMed: 38622537
DOI: 10.1186/s12886-024-03419-4 -
Clinical Case Reports Mar 2024Primary GBM of the optic nerve and chiasma should be included in the differential diagnosis of progressive lesions despite initial treatment; clinicians should avoid...
KEY CLINICAL MESSAGE
Primary GBM of the optic nerve and chiasma should be included in the differential diagnosis of progressive lesions despite initial treatment; clinicians should avoid delay in confirming the histology to initiate proper treatment and improve prognosis.
ABSTRACT
Primary GBM of the optic nerve or chiasma is very rare. The characteristics of this condition have not been well-described, which poses difficulties in establishing the correct diagnosis, affecting the treatment and the prognosis. We present a case of GBM of the optic chiasma diagnosed through an open biopsy at our centre. Following the PRISMA statement, we also conducted a systematic review after protocol registration in PROSPERO (CRD42021285855). We searched Medline and Embase through Ovid from inception until December 31, 2021. Two reviewers independently screened the studies. Studies were eligible for inclusion if they reported cases of primary GBM confined to the optic nerve or chiasma as the initial radiological diagnosis. A 77-year-old female was referred for progressive visual loss lasting 8 weeks. MRI revealed a suspected lesion in the left chiasma. The patient's vision deteriorated further despite initially diagnosing an inflammatory process and empirical treatment with corticosteroids. Subsequently, the patient underwent an open biopsy and surgical debulking. Histology, including epigenetic analysis, confirmed GBM grade IV. Radiochemotherapy was administered. The patient died 19 months after surgery. We identified 45 similar cases (22 female) reported in 35 studies between 1949 and 2020. The mean age of the cases was 61 (SD = 14.6). Most cases were misdiagnosed and mistreated accordingly, so there was a median delay of 8 weeks (IQR: 5-14 weeks) in obtaining histological confirmation of the diagnosis, delaying the initiation of appropriate treatment. Five cases became no treatment since the patients died shortly after the delayed histologic diagnosis. The Kaplan-Meier estimate indicated that most patients died within 20 months of presentation, with a 1-year survival rate of 50%, and untreated cases had very low survival rates compared to treated cases. Primary GBM of the optic nerve and chiasma is a rare condition primarily affecting adults. The rarity of this condition contributes to initial misdiagnosis, mistreatment, and delays in confirming the histology and initiating appropriate treatment. The prognosis remains poor, but treatment, including surgery and radiochemotherapy, improves survival.
PubMed: 38515994
DOI: 10.1002/ccr3.8636 -
Aging and Disease Mar 2024Although researched extensively the understanding regarding mechanisms underlying glaucoma pathogenesis remains limited. Further, the exact mechanism behind neuronal... (Review)
Review
Although researched extensively the understanding regarding mechanisms underlying glaucoma pathogenesis remains limited. Further, the exact mechanism behind neuronal death remains elusive. The role of neuroinflammation in retinal ganglion cell (RGC) death has been prominently theorised. This review provides a comprehensive summary of neuroinflammatory responses in glaucoma. A systematic search of Medline and Embase for articles published up to 8th March 2023 yielded 32 studies using post-mortem tissues from glaucoma patients. The raw data were extracted from tables and text to calculate the standardized mean differences (SMDs). These studies utilized post-mortem tissues from glaucoma patients, totalling 490 samples, compared with 380 control samples. Among the included studies, 27 reported glial cell activation based on changes to cellular morphology and molecular staining. Molecular changes were predominantly attributed to astrocytes (62.5%) and microglia (15.6%), with some involvement of Muller cells. These glial cell changes included amoeboid microglial cells with increased CD45 or HLA-DR intensity and hypertrophied astrocytes with increased glial fibrillary acidic protein labelling. Further, changes to extracellular matrix proteins like collagen, galectin, and tenascin-C suggested glial cells' influence on structural changes in the optic nerve head. The activation of DAMPs-driven immune response and the classical complement cascade was reported and found to be associated with activated glial cells in glaucomatous tissue. Increased pro-inflammatory markers such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were also linked to glial cells. Glial cell activation was also associated with mitochondrial, vascular, metabolic and antioxidant component disruptions. Association of the activated glial cells with pro-inflammatory responses, dysregulation of homeostatic components and antigen presentation indicates that glial cell responses influence glaucoma progression. However, the exact mechanism triggering these responses and underlying interactions remains unexplored. This necessitates further research using human samples for an increased understanding of the precise role of neuroinflammation in glaucoma progression.
PubMed: 38502591
DOI: 10.14336/AD.2024.0103 -
Multiple Sclerosis and Related Disorders May 2024Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by relapses of inflammation and demyelination primarily affecting the optic nerve... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by relapses of inflammation and demyelination primarily affecting the optic nerve and the spinal cord. C5 complement inhibition is an effective therapeutic approach in the treatment of NMOSD. In this systematic review and meta-analysis, we aimed to determine the role of C5 inhibitors in the treatment of patients with seropositive anti-aquaporin-4 antibody (AQP4+IgG) NMOSD.
METHODS
This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Relevant articles were systematically searched through Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases until October 6th, 2023. We included randomized clinical trials (RCTs) that investigated the treatment with C5 inhibitors compared to placebo in patients with seropositive NMOSD. The primary endpoint was the rates of first adjudicated relapse. Secondary endpoints included different disability and quality of life measures. The random-effects model was used for all statistical analyses.
RESULTS
Two RCTs with a total of 201 patients were included. C5 inhibitors demonstrated significant reduction of first adjudicated relapse (risk ratio (RR) = 0.05, 95 % CI 0.01-0.15) and Hauser Ambulation Index (HAI) (mean difference (MD): -0.79, 95 % CI -1.27 to -0.31). There was no significant difference between the two groups in Expanded Disability Status Scale (EDSS) (MD -0.23, 95 % CI -0.54-0.08). C5 inhibitors significantly improved the mean change in EQ-5D index (MD 0.08, 95 % CI 0.01-0.14; P = 0.02); however, no significant difference was shown in the mean change in EQ-5D VAS (MD 3.79, 95 % CI -1.61 to 9.19; P = 0.17). Safety measures were comparable between C5 inhibitors and placebo.
CONCLUSION
NMOSD Patients with AQP4+IgG receiving C5 inhibitors have lower rate of relapses and improved levels of disability and quality of life. Real-world studies are warranted to establish the long-term safety of C5 inhibitors.
Topics: Neuromyelitis Optica; Humans; Aquaporin 4; Autoantibodies; Complement C5; Randomized Controlled Trials as Topic
PubMed: 38479045
DOI: 10.1016/j.msard.2024.105524 -
PloS One 2024Intraocular pressure is the only modifiable risk factor for the development and progression of glaucoma. Raised intraocular pressure could cause progressive visual field... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intraocular pressure is the only modifiable risk factor for the development and progression of glaucoma. Raised intraocular pressure could cause progressive visual field loss and blindness if left uncontrolled. Adherence to ocular hypotensive medications is vital to prevent optic nerve damage and its consequences. This study was conducted to systematically summarize the magnitude of glaucoma medication adherence and factors influencing adherence to glaucoma medications among adult glaucoma patients in Ethiopia.
METHODS
Database searches to identify research articles were conducted on PubMed, EMBASE, Cochrane, AJOL, SCOPUS, and Google Scholar without restriction on the date of publication. Data extraction was done using a data extraction Excel sheet. Analysis was performed using STATA version 16. Heterogeneity was assessed using I2 statistics. Pooled prevalence and pooled odds ratio with a 95% confidence interval using a random effect model were computed.
RESULT
We included six studies with a total of 2101 participants for meta-analysis. The magnitude of adherence to glaucoma medication was found to be 49.46% (95% CI [41.27-57.66]). Urban residents (OR = 1.89, 95% CI; 1.29-2.49) and those with normal visual acuity (OR = 2.82, 95% CI; 0.85-4.80) had higher odds of adherence to glaucoma medications. Patients who pay for the medications themselves (OR = 0.22, 95% CI; 0.09-0.34) were found to have 78% lower odds of adherence than their counterparts.
CONCLUSION
The magnitude of glaucoma medication adherence is lower than expected. Place of residence, visual acuity, and payment means had statistically significant associations with glaucoma medication adherence. Tailored health education on medication adherence and subsidization of glaucoma medication is recommended.
Topics: Adult; Humans; Ethiopia; Glaucoma; Antihypertensive Agents; Intraocular Pressure; Medication Adherence
PubMed: 38478513
DOI: 10.1371/journal.pone.0293047 -
Eye (London, England) Jun 2024Addressing Dysthyroid Optic Neuropathy (DON) is crucial due to its debilitating impact in thyroid eye disease (TED). Prompt treatment can preserve vision. Despite... (Meta-Analysis)
Meta-Analysis
PURPOSE
Addressing Dysthyroid Optic Neuropathy (DON) is crucial due to its debilitating impact in thyroid eye disease (TED). Prompt treatment can preserve vision. Despite lacking definitive diagnostic criteria, computed tomography's (CT) parameters are commonly used for diagnosis. However, these parameters exist without consensus on their diagnostic performance.
DESIGN
Systematic review and meta-analysis.
METHODS
We conducted a meta-analysis of studies assessing orbital CT diagnostic performance for DON in adults with TED. We searched various databases including Medline, PubMed, Scopus, and EMBASE, and others electronic databases, until July 2023. Evaluated CT parameters includes Barrett index (BI), fat prolapse via superior-orbital-fissure (SOF), superior-ophthalmic-vein-dilatation (SOVD), and the Nugent score. Diagnostic Test Accuracy analysis (DTA) was performed using R.
RESULTS
A total of 9 articles with documented target parameters, collectively analysed 212 orbits with DON. Nugent score exhibited highest diagnostic ability with a log diagnostic odd ratio (logDOR) of 2.64 (95% CI, 2.02, 3.25). Another significant DON indicator was a BI ≥ 50%, with a logDOR of 1.97 (95% CI, 1.17; 2.77). Conversely, fat prolapse via SOF and SOVD proved less sensitive, with a logDOR of 1.42 and 1.09 respectively. Regarding the SROC curve, Nugent score and the BI have the greatest AUC. Variations in study locale, participant demographics, and measurement methods accounted for heterogeneity in meta-analysis.
CONCLUSIONS
Nugent score and a BI ≥ 50% prove to be significant diagnostic parameters for DON, distinguishing them from fat prolapse via SOF and SOVD. Prioritizing these parameters can lead to prompt treatment and thus enhanced visual outcomes.
PROSPERO REGISTRATION NUMBER
CRD42023446376.
Topics: Humans; Graves Ophthalmopathy; Tomography, X-Ray Computed; Optic Nerve Diseases; Orbit
PubMed: 38472378
DOI: 10.1038/s41433-024-03011-6 -
Ocular Immunology and Inflammation Feb 2024To assess fetal and neonatal eyes abnormalities and their progression during the last ZIKV outbreak and summarize learned lessons. (Review)
Review
OBJECTIVE
To assess fetal and neonatal eyes abnormalities and their progression during the last ZIKV outbreak and summarize learned lessons.
METHODS
A systematic review and meta-analysis was conducted by a team of obstetricians and ophthalmologists.
RESULTS
Studies reporting ocular abnormalities during the prenatal ( = 5) and postnatal ( = 24) periods were included in the analysis. In the prenatal period, the most common ocular findings were intraocular calcification cases (4/6, 66.6%) and microphthalmia (3/6, 50%). Postnatal ocular abnormalities of congenital ZIKV infection were described after birth in 479 cases. Among them microphthalmia was reported in 13 cases (13/479, 2.7%). Posterior segment (retina and optic nerve) was the most affected structure, consisting of pigmentary changes (229/479, 47.8%), macular chorioretinal atrophy (216/479, 45%), optic nerve atrophy (181/479, 37.8%), increased cup-to-disk ratio (190/479, 39.6.%), optic nerve hypoplasia (93/479,19.4%), vascular changes (26/479, 5.4%), and retinal coloboma (20/479, 4.1%). The anterior segment was involved in 4.6% (22/479) of cases, including cataract (9/479, 1.8%), lens subluxation (1/479, 0.2%), iris coloboma (5/479, 1%), and congenital glaucoma (7/479, 1.4%). These ocular anomalies were isolated in one case (1/479, 0.2%) and multiple anomalies were found in the other cases. Long-term visual disorders have been described, with no possible improvement and even a worsening of some of the ocular anomalies previously observed. No reactivation of ocular lesions was observed.
CONCLUSION
This review highlights the severe ocular abnormalities associated with congenital ZIKV infections. The importance of multidisciplinary communication between the obstetrician, the maternal-fetal medicine specialist, and the ophthalmologist is emphasized.
PROTOCOL REGISTRATION
This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration440 188.
PubMed: 38350011
DOI: 10.1080/09273948.2024.2314086 -
Ontario Health Technology Assessment... 2024Glaucoma is the term for a group of eye disorders that causes progressive damage to the optic nerve, which can lead to visual impairment and, potentially, irreversible...
BACKGROUND
Glaucoma is the term for a group of eye disorders that causes progressive damage to the optic nerve, which can lead to visual impairment and, potentially, irreversible blindness. Minimally invasive bleb surgery (MIBS) reduces eye pressure through the implantation of a device that creates a new subconjunctival outflow pathway for eye fluid drainage. MIBS is a less invasive alternative to conventional/incisional glaucoma surgery (e.g., trabeculectomy). We conducted a health technology assessment of MIBS for people with glaucoma, which included an evaluation of effectiveness, safety, the budget impact of publicly funding MIBS, and patient preferences and values.
METHODS
We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane Risk of Bias 1.0 tool for randomized controlled trials (RCTs) and the Risk of Bias Assessment tool for Nonrandomized Studies (RoBANS) for comparative observational studies, and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We conducted an economic literature search and we estimated the budget impact of publicly funding MIBS in Ontario. We did not conduct a primary economic evaluation due to the limited long-term effectiveness data. We summarized the preferences and values evidence from previous health technology assessments to understand the perspectives and experiences of patients with glaucoma.
RESULTS
We included 41 studies (2 RCTs and 39 comparative observational studies) in the clinical evidence review. MIBS may reduce intraocular pressure and the number of medications used, but we are uncertain if MIBS results in outcomes similar to trabeculectomy (GRADE: Moderate to Very low). Compared with trabeculectomy, MIBS may result in fewer follow-up visits and interventions, and adverse events (GRADE: Moderate to Very Low). MIBS may also reduce intraocular pressure and the number of antiglaucoma medications used, compared with other glaucoma treatments, but the evidence is uncertain (GRADE: Very low). Our economic evidence review identified two directly applicable studies. The results of these studies indicate that the cost-effectiveness of MIBS is highly uncertain, and the cost of glaucoma interventions are likely to vary across provinces. The annual budget impact of publicly funding MIBS in Ontario ranged from $0.11 million in year 1 to $0.67 million in year 5, for a total 5-year budget impact estimate of $1.93 million. Preferences and values evidence suggests that fear of ultimate blindness and difficulty managing medication for glaucoma led patients to explore other treatment options such as MIBS. Glaucoma patients found minimally invasive glaucoma surgery (MIGS) procedure beneficial, with minimal side effects and recovery time.
CONCLUSIONS
Minimally invasive bleb surgery reduces intraocular eye pressure and the number of antiglaucoma medications needed, but we are uncertain if the outcomes are similar to trabeculectomy (GRADE: Moderate to Very low). However, MIBS may be safer than trabeculectomy (GRADE: Moderate to Very low) and result in fewer follow-ups (GRADE: Moderate to Very low). MIBS may also improve glaucoma symptoms compared with other glaucoma treatments, but the evidence is very uncertain (GRADE: Very low).We estimate that publicly funding MIBS would result in an additional cost of $1.93 million over 5 years. Patients who underwent MIGS procedures found them to be generally successful and beneficial, with minimal side effects and recovery time. We could not draw conclusions about specific MIBS procedures or long-term outcomes.
Topics: Humans; Antiglaucoma Agents; Blindness; Glaucoma; Technology Assessment, Biomedical; Trabeculectomy; Clinical Trials as Topic
PubMed: 38332948
DOI: No ID Found -
Ophthalmic Research 2024Anterior ischemic optic neuropathy (AION) can mimic glaucoma and consequently cause difficulties in differential diagnosis. The purpose of this paper was to summarize... (Review)
Review
INTRODUCTION
Anterior ischemic optic neuropathy (AION) can mimic glaucoma and consequently cause difficulties in differential diagnosis. The purpose of this paper was to summarize differences in diagnostic tests that can help perform a correct diagnosis.
METHODS
The search strategy was performed according to the PRISMA 2009 guidelines, and four databases were used: MEDLINE, Embase, Web of Science, and Cochrane. Totally, 772 references were eligible; 39 were included after screening with respect to inclusion criteria that included English language and published in the 20 years before search date.
RESULTS
Ninety percent (n = 35) of included studies used optical coherence tomography (OCT). Glaucomatous eyes had a significantly greater cup area, volume and depth, cup-to-disk ratio, a lower rim volume and area, and a thinner Bruch's membrane opening-minimum rim width. Retinal nerve fiber layer (RNFL) thinning in glaucomatous eyes occurred primarily at the superotemporal, inferotemporal, and inferonasal sectors, while AION eyes demonstrated mostly superonasal thinning. Glaucoma eyes showed greater macular ganglion cell layer thickness, except at the inferotemporal sector. OCT angiography measurements demonstrated a significant decrease in superficial and deep macular vessel density (VD) in glaucoma compared to AION with similar degree of visual field damage; the parapapillary choroidal VD was spared in AION eyes compared to glaucomatous eyes.
CONCLUSION
By use of OCT imaging, optic nerve head parameters seem most informative to distinguish between glaucoma and AION. Although both diseases affect the RNFL thickness, it seems to do so in different sectors. Differences in structure and vascularity of the macula can also help in making the differential diagnosis.
Topics: Humans; Optic Neuropathy, Ischemic; Diagnosis, Differential; Tomography, Optical Coherence; Nerve Fibers; Retinal Ganglion Cells; Optic Disk; Glaucoma; Visual Fields; Intraocular Pressure
PubMed: 38262372
DOI: 10.1159/000535568 -
Neurosurgical Review Jan 2024Cavernomas are histologically benign vascular malformations found at different sites in the brain. A rare site for such cavernomas, however, is the anterior optic... (Review)
Review
Cavernomas are histologically benign vascular malformations found at different sites in the brain. A rare site for such cavernomas, however, is the anterior optic pathway, comprising the optic nerve, chiasma, and optic tract-called optochiasmatic cavernomas (OCC). These lesions usually present with sudden onset or progressive vision loss, headache, and features mimicking pituitary apoplexy. In this paper, we describe a case of OCC operated at our center. We carry out an updated review of literature depicting cases of OCC, their clinical presentation, management, and postoperative complications. We also propose a novel classification system based on lesion location and further analyze these cavernoma types with respect to the surgical approach used and visual outcome. A 30-year-old lady had presented with a 3-week history of progressive bilateral vision loss and headache. Based on imaging, she was suspected to have a cavernous angioma of the chiasma and left optic tract. Due to progressive vision deterioration, the lesion was surgically excised using pterional craniotomy. Postoperatively, her visual symptoms improved, but she developed diabetes insipidus. Clinical and radiological follow-up has been done for 18 months after surgery. A total of 81 cases have been described in the literature, including the present case. Chiasmal apoplexy is the most common presentation. Surgical excision is the standard of care. Our analysis based on lesion location shows the most appropriate surgical approach to be used for each cavernoma type. Visual outcome correlates with the preoperative visual status. Visual outcome is good in patients presenting with acute chiasmal apoplexy, and when complete surgical excision is performed. The endonasal endoscopic approach was found to provide the best visual outcome. In addition to preoperative visual status, complete surgical excision predicts favorable visual outcomes in OCC. Our proposed classification system guides the appropriate surgical approach required for a particular location of the cavernoma.
Topics: Adult; Female; Humans; Headache; Hemangioma, Cavernous; Optic Chiasm; Optic Nerve; Stroke; Vision Disorders
PubMed: 38238497
DOI: 10.1007/s10143-024-02288-1