To compare the efficacy, safety, and risk factors for failure of standalone ab interno gelatin microstent implantation with mitomycin C (MMC) versus trabeculectomy with MMC.
International, ...multicenter, retrospective interventional cohort study.
Three hundred fifty-four eyes of 293 patients (185 microstent and 169 trabeculectomy) with no prior incisional surgery.
Consecutive eyes with uncontrolled glaucoma underwent microstent or trabeculectomy surgery from January 1, 2011 through July 31, 2015 at 4 academic ophthalmology centers: Toronto, Canada; Frankfurt, Germany; Salzburg, Austria; and Leuven, Belgium.
Primary outcome measure was hazard ratio (HR) of failure, with failure defined as 2 consecutive intraocular pressure (IOP) readings of <6 mmHg with vision loss or >17 mmHg without glaucoma medications (complete success) at least 1 month after surgery despite in-clinic interventions (including needling). Secondary outcome measures included IOP thresholds of 6 to 14 mmHg and 6 to 21 mmHg and same thresholds allowing for medications (qualified success), interventions, complications, and reoperations.
Baseline characteristics were similar, except more men (56% vs. 43%), younger patients (average, by 3 years), better preoperative visual acuity (22% vs. 32% with 0.4 logarithm of the minimum angle of resolution vision or worse), and more trabeculoplasty (52% vs. 30%) among microstent eyes. The adjusted HR of failure of the microstent relative to trabeculectomy was 1.2 (95% confidence interval CI, 0.7-2.0) for complete success and 1.3 (95% CI, 0.6-2.8) for qualified success, and similar for other outcomes. Time to 25% failure was 11.2 months (95% CI, 6.9-16.1 months) and 10.6 months (95% CI, 6.8-16.2 months) for complete success and 30.3 months (95% CI, 19.0-∞ months) and 33.3 months (95% CI, 25.7-46.2 months) for qualified success. Overall, white ethnicity was associated with decreased risk of failure (adjusted HR, 0.49; 95% CI, 0.25-0.96), and diabetes was associated with increased risk of failure (adjusted HR, 4.21; 95% CI, 2.10-8.45). There were 117 and 165 distinct interventions: 43% and 31% underwent needling, respectively, and 50% of trabeculectomy eyes underwent laser suture lysis. There were 22 and 30 distinct complications, although most were transient. Ten percent and 5% underwent reoperation (P = 0.11).
There was no detectable difference in risk of failure and safety profiles between standalone ab interno microstent with MMC and trabeculectomy with MMC.
Although unprecedented sensitivity and specificity values are reported, recent glaucoma detection deep learning models lack in decision transparency. Here, we propose a methodology that advances ...explainable deep learning in the field of glaucoma detection and vertical cup-disc ratio (VCDR), an important risk factor. We trained and evaluated deep learning models using fundus images that underwent a certain cropping policy. We defined the crop radius as a percentage of image size, centered on the optic nerve head (ONH), with an equidistant spaced range from 10-60% (ONH crop policy). The inverse of the cropping mask was also applied (periphery crop policy). Trained models using original images resulted in an area under the curve (AUC) of 0.94 95% CI 0.92-0.96 for glaucoma detection, and a coefficient of determination (R
) equal to 77% 95% CI 0.77-0.79 for VCDR estimation. Models that were trained on images with absence of the ONH are still able to obtain significant performance (0.88 95% CI 0.85-0.90 AUC for glaucoma detection and 37% 95% CI 0.35-0.40 R
score for VCDR estimation in the most extreme setup of 60% ONH crop). Our findings provide the first irrefutable evidence that deep learning can detect glaucoma from fundus image regions outside the ONH.
Ocular manifestations in several neurological pathologies accentuate the strong relationship between the eye and the brain. Retinal alterations in particular can serve as surrogates for cerebral ...changes. Offering a "window to the brain," the transparent eye enables non-invasive imaging of these changes in retinal structure and vasculature. Fractal dimension (FD) reflects the overall complexity of the retinal vasculature. Changes in FD could reflect subtle changes in the cerebral vasculature that correspond to preclinical stages of neurodegenerative diseases. In this review, the potential of this retinal vessel metric to serve as a biomarker in neurodegeneration and stroke will be explored.
A literature search was conducted, following the PRISMA Statement 2009 criteria, in four large bibliographic databases (Pubmed, Embase, Web Of Science and Cochrane Library) up to 12 October 2019. Articles have been included based upon their relevance. Wherever possible, level of evidence (LOE) has been assessed by means of the Oxford Centre for Evidence-based Medicine Level of Evidence classification.
Twenty-one studies were included for qualitative synthesis. We performed a narrative synthesis and produced summary tables of findings of included papers because methodological heterogeneity precluded a meta-analysis. A significant association was found between decreased FD and neurodegenerative disease, mainly addressing cognitive impairment (CI) and dementia. In acute, subacute as well as chronic settings, decreased FD seems to be associated with stroke. Differences in FD between subtypes of ischemic stroke remain unclear.
This review provides a summary of the scientific literature regarding the association between retinal FD and neurodegenerative disease and stroke. Central pathology is associated with a decreased FD, as a measure of microvascular network complexity. As retinal FD reflects the global integrity of the cerebral microvasculature, it is an attractive parameter to explore. Despite obvious concerns, mainly due to a lack of methodological standardization, retinal FD remains a promising non-invasive and low-cost diagnostic biomarker for neurodegenerative and cerebrovascular disease. Before FD can be implemented in clinic as a diagnostic biomarker, the research community should strive for uniformization and standardization.
Glaucoma is one of the world's most common blinding diseases, affecting more than 60 million people worldwide. Although the disease presents as a neurodegenerative disorder affecting retinal ganglion ...cell axons in the optic nerve and their somata in the retina, the elicitors of this optic neuropathy are often located outside the neuroretina. Disturbances in aqueous humor outflow, leading to ocular hypertension, are considered to be the major risk factor for the development of glaucoma. Although an amplitude of pharmacological and surgical measures is available to lower IOP in glaucoma patients, these are not always sufficient to halt the disease. Multiple surveys in glaucoma patients, as well as in vitro studies in anterior segment explant or cell cultures, reported changes in the expression and activity of several matrix metalloproteinases (MMPs) in the aqueous humor and trabecular meshwork, in response to elevated IOP. In this review, we describe MMPs as important modulators of aqueous humor outflow, functioning in a feedback mechanism that continuously remodels the trabecular meshwork extracellular matrix composition in order to maintain a stable outflow resistance and IOP. We review the evidence for the involvement of MMPs in glaucoma disease onset and investigate their potential as therapeutic targets for the development of future glaucoma therapies.
Purpose
Elevated intra‐ocular pressure (IOP) has been identified as a major risk factor for glaucoma. Additionally, extensive literature depicts a vascular dysfunction to exist in these patients. ...However, a large ocular blood flow‐oriented trial to integrate these findings in the clinical setting is lacking. This study would likely help to identify which of these vascular data can be used as a clinical tool for screening and disease stratification.
Method
Prospective, cross‐sectional, case–control hospital‐based study. Patients with primary open‐angle glaucoma (POAG), normal‐tension glaucoma (NTG), ocular hypertension (OHT), glaucoma suspects and healthy volunteers were recruited. In addition to a comprehensive ophthalmological examination, a vascular‐oriented questionnaire was completed and ocular blood flow assessment (colour Doppler imaging of retrobulbar vessels, retinal oximetry, dynamic contour tonometry, optical coherent tomography enhanced‐depth imaging of the choroid) were performed. Statistical analysis was based on multiple imputation to account for missingness.
Results
A total of 614 subjects (291 males) were recruited between March and December 2013 (POAG: 214, NTG: 192; OHT: 27; glaucoma suspect: 41; healthy controls: 140). Glaucoma groups (NTG and POAG) were age and gender matched with the control group (p > 0.05). Glaucoma groups were paired in terms of functional and structural parameters (p > 0.08). Mean ocular perfusion pressure was higher in the glaucoma groups than in controls (p < 0.001). Glaucoma groups had lower retrobulbar velocities, higher retinal venous saturation and choroidal thickness asymmetries when compared to the healthy group, in line with the current literature.
Conclusions
The Leuven Eye Study stands as one of the largest clinical trials on ocular blood flow in glaucoma. The creation of this vast database may help integrate the vascular aspects of glaucoma into the clinical practice of glaucoma.
The goal of this study was to perform an extensive temporal characterization of the early pathologic processes in the streptozotocin (STZ)-induced diabetic retinopathy (DR) mouse model, beyond the ...vascular phenotype, and to investigate the potential of clinically relevant compounds in attenuating these processes.
Visual acuity and contrast sensitivity (CS) were studied in the mouse STZ model until 24 weeks postdiabetes onset. ERG, spectral domain optical coherence tomography (SD-OCT), leukostasis, and immunohistochemistry were applied to investigate neurodegeneration, inflammation, and gliosis during early-, mid- and late-phase diabetes. Aflibercept or triamcinolone acetonide (TAAC) was administered to investigate their efficacy on the aforementioned processes.
Visual acuity and CS loss started at 4 and 18 weeks postdiabetes onset, respectively, and progressively declined over time. ERG amplitudes were diminished and OP latencies increased after 6 weeks, whereas SD-OCT revealed retinal thinning from 4 weeks postdiabetes. Immunohistochemical analyses linked these findings to retinal ganglion and cholinergic amacrine cell loss at 4 and 8 weeks postdiabetes onset, respectively, which was further decreased after aflibercept administration. The number of adherent leukocytes was augmented after 2 weeks, whereas increased micro- and macroglia reactivity was present from 4 weeks postdiabetes. Aflibercept or TAAC showed improved efficacy on inflammation and gliosis.
STZ-induced diabetic mice developed early pathologic DR hallmarks, from which inflammation seemed the initial trigger, leading to further development of functional and morphologic retinal changes. These findings indicate that the mouse STZ model is suitable to study novel integrative non-vascular therapies to treat early DR.
Due to a prolonged life expectancy worldwide, the incidence of age-related neurodegenerative disorders such as glaucoma is increasing. Glaucoma is the second cause of blindness, resulting from a slow ...and progressive loss of retinal ganglion cells (RGCs) and their axons. Up to now, intraocular pressure (IOP) reduction is the only treatment modality by which ophthalmologists attempt to control disease progression. However, not all patients benefit from this therapy, and the pathophysiology of glaucoma is not always associated with an elevated IOP. These limitations, together with the multifactorial etiology of glaucoma, urge the pressing medical need for novel and alternative treatment strategies. Such new therapies should focus on preventing or retarding RGC death, but also on repair of injured axons, to ultimately preserve or improve structural and functional connectivity. In this respect, Rho-associated coiled-coil forming protein kinase (ROCK) inhibitors hold a promising potential to become very prominent drugs for future glaucoma treatment. Their field of action in the eye does not seem to be restricted to IOP reduction by targeting the trabecular meshwork or improving filtration surgery outcome. Indeed, over the past years, important progress has been made in elucidating their ability to improve ocular blood flow, to prevent RGC death/increase RGC survival and to retard axonal degeneration or induce proper axonal regeneration. Within this review, we aim to highlight the currently known capacity of ROCK inhibition to promote neuroprotection and regeneration in several in vitro, ex vivo and in vivo experimental glaucoma models.
This study aimed to describe the clinical findings and management of eyes affected by uveal effusion syndrome.
We retrospectively evaluated the charts of 13 eyes of 8 consecutive patients diagnosed ...with uveal effusion syndrome attending the Ophthalmology Unit of the University Hospitals Leuven, Belgium, between 2007 and 2018. The presenting features, investigations, management, and outcomes were analyzed for each case.
Cataract surgery was the predisposing factor for uveal effusion in 6 eyes, 2 bilateral uveal effusions (4 eyes) were considered to be medication-induced, and in 3 eyes, the uveal effusion was described as idiopathic. Fundus examination of 5 of 13 eyes showed bullous choroidal detachment, treated with pars plana vitrectomy with superotemporal sclerectomy or transscleral punction. Fundoscopy showed uveal effusion without serous retinal detachment in 3 eyes. Serous retinal detachment accompanied by uveal swelling was observed in 3 eyes and the 2 remaining eyes presented with uveal swelling only. The 8 nonbullous choroidal detachments were treated in a conservative way. A rapid resolution of subretinal fluid and uveal effusion was observed in all cases.
A conservative approach with acetazolamide treatment or just observation was used in our case series in choroidal detachment without substantial visual loss if, over time, slow improvement was documented. However, further studies are needed to verify the effectiveness of the reported therapy.
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