Open-angle glaucoma (OAG) is characterized by optic nerve fiber atrophy and deterioration of the visual field, corresponding to damage to the optic nerve head. Intraocular pressure (IOP) is currently ...the only evidence-based, treatable risk factor for OAG. However, normal-tension glaucoma, the most common type of OAG in Asia, is a type of glaucoma with an unclear pathogenesis. Glaucoma is suspected to be a multifactorial disease with IOP-dependent and IOP-independent risk factors, including decreased ocular blood flow (OBF), oxidative stress, decreased axoplasmic flow, and genetic background. A number of epidemiological studies have generated strong evidence that OBF may be an especially important risk factor for the progression of glaucoma. Recent innovations in laser speckle flowgraphy and optical coherence tomography-based angiography have allowed us to noninvasively monitor changes in the microcirculation of the optic nerve head with high reproducibility. Laser speckle flowgraphy-derived measurement parameters include mean blur rate and pulse wave form parameters, whereas the main optical coherence tomography angiography-derived parameter is the vessel index. Decreases in these parameters are associated with the severity of glaucomatous damage, and changes are detectible even in the earliest, preperimetric stage of glaucoma. In the future, OBF analysis may improve significantly because of continuing progress in the development of the relevant instruments. This review will summarize possible connections between systemic and OBF abnormalities and OAG, describe the scientific rationale for these connections, and discuss their potential implications. Thus, this review will summarize the role of OBF in glaucoma pathogenesis and discuss the wide range of IOP-independent risk factors.
What is glaucomatous optic neuropathy? Nakazawa, Toru; Fukuchi, Takeo
Japanese journal of ophthalmology,
05/2020, Letnik:
64, Številka:
3
Journal Article
Recenzirano
Glaucomatous optic neuropathy (GON) is the pathohistological feature of glaucoma in the optic nerve. The pathogenesis of GON has been hypothesized, to either originate from compromised mechanical ...conditions at the lamina cribrosa or as associated with pathological vascular involvement. From a historical perspective, glaucoma is the degeneration of retinal ganglion cells (RGC) due to the elevation of intraocular pressure (IOP). The consensus of glaucoma treatment is generally accepted as sufficient IOP reduction. Is there an additional option to treat GON from the perspective of the vascular theory? In this section, two distinguished leaders in glaucoma research advance their views and discuss the current opinions surrounding the two theories regarding the causes of GON in primary open angle glaucoma (POAG) and normal tension glaucoma (NTG).
Supplementing wildtype copies of functionally defective genes with adeno-associated virus (AAV) is a strategy being explored clinically for various retinal dystrophies. However, the low cargo limit ...of this vector allows its use in only a fraction of patients with mutations in relatively small pathogenic genes. To overcome this issue, we developed a single AAV platform that allows local replacement of a mutated sequence with its wildtype counterpart, based on combined CRISPR-Cas9 and micro-homology-mediated end-joining (MMEJ). In blind mice, the mutation replacement rescued approximately 10% of photoreceptors, resulting in an improvement in light sensitivity and an increase in visual acuity. These effects were comparable to restoration mediated by gene supplementation, which targets a greater number of photoreceptors. This strategy may be applied for the treatment of inherited disorders caused by mutations in larger genes, for which conventional gene supplementation therapy is not currently feasible.
Rhegmatogenous retinal detachment (RRD) is a serious condition that can cause blindness without surgical treatment. RRD occurs when a retinal tear or hole allows fluid to accumulate below the retinal ...surface, causing the retina to separate from the underlying layers. RRD is difficult to treat because each case is unique, varying with the location, size, and duration of the detachment, as well as patient age. The first successful methods to reattach the retina in RRD used thermocautery to repair the detachment. Many renowned ophthalmologists continued to study RRD and developed many new surgical approaches, notably: scleral buckling (SB), in which a silicone band is placed around the eye to reduce traction on the retina caused by the vitreous humor that fills the eye; pars plana vitrectomy (PPV), which eliminates traction on the retina by removing the vitreous; and pneumatic retinopexy (PR), in which the retina is reattached by pushing it back into place with an expanding gas bubble injected into the eye. However, no consensus has been reached on which approach is ideal. Furthermore, recent surgical and non-surgical breakthroughs, such as artificial vitreous substitutes and neuroprotective drugs, must also be considered. Thus, this review provides a guide for ocular specialists and non-specialists on the historical background of RRD, summarizes the three current main techniques (SB, PR and PPV) compares these three techniques, and provides an overview of new technologies that promise to greatly improve outcomes after RRD surgery.
Deep learning is being employed in disease detection and classification based on medical images for clinical decision making. It typically requires large amounts of labelled data; however, the sample ...size of such medical image datasets is generally small. This study proposes a novel training framework for building deep learning models of disease detection and classification with small datasets. Our approach is based on a hierarchical classification method where the healthy/disease information from the first model is effectively utilized to build subsequent models for classifying the disease into its sub-types via a transfer learning method. To improve accuracy, multiple input datasets were used, and a stacking ensembled method was employed for final classification. To demonstrate the method's performance, a labelled dataset extracted from volumetric ophthalmic optical coherence tomography data for 156 healthy and 798 glaucoma eyes was used, in which glaucoma eyes were further labelled into four sub-types. The average weighted accuracy and Cohen's kappa for three randomized test datasets were 0.839 and 0.809, respectively. Our approach outperformed the flat classification method by 9.7% using smaller training datasets. The results suggest that the framework can perform accurate classification with a small number of medical images.
To investigate the association of systemic oxidative stress markers and optic nerve head (ONH) blood flow in normal-tension glaucoma (NTG) patients, as well as sex differences in this association.
...This was a cross-sectional study of 235 eyes with NTG of 134 patients (56 male, 78 female; mean age, 60.9±14.1 years). Laser speckle flowgraphy (LSFG) was used to measure ONH blood flow (mean blur rate in the tissue area of the ONH; MBR-T) and LSFG pulse-waveform parameters, including flow acceleration index in the tissue area of the ONH (FAI-T). Oxidative stress markers, diacron-reactive oxygen metabolites (d-ROMs), and biological antioxidant potential (BAP) were measured with a free radical elective evaluator. Spearman's rank correlation test and a multivariate linear mixed-effect model were used to investigate factors associated with ONH blood flow.
MBR-T was significantly correlated with age (rs = -0.28, p < 0.001), mean arterial pressure (rs = -0.20, p = 0.002), intraocular pressure (rs = 0.24, p < 0.001), peripapillary retinal nerve fiber layer thickness (rs = 0.62, p < 0.001), and disc area (rs = -0.26, p < 0.001), but not with serum d-ROM level. Separate analyses of the subjects divided by sex showed that BAP was positively correlated to MBR-T (rs = 0.21, p = 0.036) and FAI-T (rs = 0.36, p < 0.001) only in male subjects. Similarly, BAP was significantly associated with MBR-T (β = 0.25, p = 0.026) and FAI-T (β = 0.37, p < 0.001) in male subjects in a multivariate linear mixed-effect model.
A lower serum antioxidant level, as indicated by BAP, was associated with reduced ONH blood flow only in male NTG patients. Our findings suggest that there are sex differences in the involvement of oxidative stress in the pathogenesis of reduced ocular blood flow in NTG.
Purpose
To determine whether choroidal blood flow (BF) is related to visual field (VF) defect severity and progression in eyes with open-angle glaucoma (OAG).
Study design
Retrospective and ...longitudinal.
Methods
This study comprised 443 eyes of 285 OAG patients who underwent laser speckle flowgraphy (LSFG), optical coherence tomography, and visual-field (VF) testing at baseline. The patients were then observed for at least 2 years and at least 5 reliable VF tests were performed. In the LSFG images, we set regions of interest at the optic nerve head (ONH) and the parapapillary choroid to obtain ONH-tissue mean blur rate (MBR) and choroidal MBR, respectively. We used univariable and multivariable linear mixed-effects models to determine clinical factors associated with choroidal MBR at baseline. We also used a linear mixed-effects model to determine the contribution of ONH-tissue MBR and choroidal MBR to baseline mean deviation (MD) and to MD slope during follow-up, adjusting for potential confounding factors, including circumpapillary retinal nerve fiber layer thickness.
Results
Choroidal MBR was associated with age, MD slope, and ONH-tissue MBR (β = -0.181,
P
= 0.001; β = 0.134,
P
= 0.002; β = 0.096,
P
= 0.049, respectively). ONH-tissue MBR was associated with both MD and MD slope (β = 0.146,
P
= 0.004; β = 0.152,
P
= 0.009, respectively), whereas choroidal MBR was associated only with MD slope (β = 0.147,
P
= 0.005).
Conclusion
LSFG-derived choroidal MBR might be a useful biomarker to predict VF defect progression in a Japanese population.
Disease/patient registries are underutilized despite their multiple advantages over clinical trials in the clinical evaluation of drugs, such as the capacity for long-term curation, provision of ...patient outcome data in routine clinical practice, and provision of benchmark data for comparison. Ensuring the fit-for-purpose quality of data generated from such registries is important to informing regulatory decision making. Here, we report the construction of a quality management system aiming to ensure regulatory-grade data quality for a registry of Japanese patients with glaucoma to evaluate long-term patient outcomes.
The quality management system was established by reference to the risk-based approach in the ICH-E6 (R2) recommendations. The following three-component approach was taken: establishment of governance, computerized system validation (CSV), and implementation of risk assessment and control. Compliance of the system with the recommendations of regulatory guidelines relevant to use of the registry was assessed.
Governance by academic collaboration was established. This was followed by the development of a total of 15 standard operating procedures, including CSV, data management, monitoring, audit, and management of imaging data. The data management system was constructed based on a data management plan, which specified data/paper flow and data management procedures. The electronic data capture (EDC) system was audited by an external vendor, and configured and validated using the V-model framework as recommended in the GAMP5 guideline. Informed consent, eligibility assessment and major ophthalmology measurements were determined as Critical to Quality (CTQ) factors. A total of 22 risk items were identified and classified into three categories, and operationalized in the form of a risk control plan, which included training sessions and risk-based monitoring. The glaucoma registry addressed most quality recommendations in official guidelines issued by multiple health authorities, although two recommendations were not met.
We established and configured a quality management system for a glaucoma registry to ensure fit-for-purpose data quality for regulatory use, and to curate long-term follow-up data of glaucoma patients in a prospective manner.
The internal limiting membrane (ILM) is a normal part of the retina, and the outcomes of ILM removal have not been fully investigated. ILM flap inversion is a recently developed technique that ...increases the success rate of macular hole (MH) surgery. Thus, we compared the anatomical closure rate and visual outcome in patients undergoing microincision vitrectomy surgery (MIVS) with ILM flap inversion or conventional ILM peeling for the treatment of MH.
The medical records of 90 eyes with MH were reviewed retrospectively. The patients were classified into two groups based on MIVS procedure (group 1: ILM flap inversion, 46 eyes; group 2: ILM peeling, 44 eyes).
Preoperative characteristics were similar in the two groups, and there were no significant differences in 1 month- or 6 month-postoperative VA between the groups (P = 0.25 and P = 0.42, respectively). However, the surgical success rate was significantly higher in group 1 than group 2 (P = 0.04; 46/46: 100% and 41/44: 93%, respectively). Multiple regression analysis revealed that axial length and MH diameter were independent factors predicting 6-month postoperative BCVA in group 2 (P = 0.001 and P = 0.03, respectively), and that MH diameter was an independent factor predicting 6-month postoperative VA in group 1 (P = 0.03). Logistic regression analysis revealed that axial length (OR = 2.11; P = 0.02; area under the curve: 0.94; cut off score: 28.4 mm) was an independent factor indicating surgical failure in group 2.
Our results suggest that MIVS with ILM flap inversion might be best suited to treat MH, particularly in patients with high myopia.
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