Damage to the retinal pigment epithelium, Bruch’s membrane and/or tissues underlying macula is known to increase the risk of age-related macular degeneration (AMD). AMD is commonly categorized in two distinct types, namely, the nonexudative (dry form) and the exudative (wet form). Currently, there is no ideal treatment available for AMD. Recommended standard treatments are based on the use of vascular endothelial growth factor (VEGF), with the disadvantage of requiring repeated intravitreal injections which hinder patient’s compliance to the therapy. In recent years, several synthetic and natural active compounds have been proposed as innovative therapeutic strategies against this disease. There is a growing interest in the development of formulations based on nanotechnology because of its important role in the management of posterior eye segment disorders, without the use of intravitreal injections, and furthermore, with the potential to prolong drug release and thus reduce adverse effects. In the same way, 3D bioprinting constitutes an alternative to regeneration therapies for the human retina to restore its functions. The application of 3D bioprinting may change the current and future perspectives of the treatment of patients with AMD, especially those who do not respond to conventional treatment. To monitor the progress of AMD treatment and disease, retinal images are used. In this work, we revised the recent challenges encountered in the treatment of different forms of AMD, innovative nanoformulations, 3D bioprinting, and techniques to monitor the progress.

/pdf/therapeutic-approaches-for-age-related-macular-degeneration-2pyth9cv.pdf

Therapeutic Approaches for Age-Related Macular Degeneration

Dark matter: Developing a new nanoantioxidant-based therapeutic system for the treatment of age-related macular degeneration

Medical specialties with access to a large amount of imaging data, such as ophthalmology, have been at the forefront of the artificial intelligence (AI) revolution in medicine, driven by deep learning (DL) and big data. With the rise of AI and big data, there has also been increasing concern on the issues of bias and privacy, which can be partially addressed by low-shot learning, generative DL, federated learning and a “model-to-data” approach, as demonstrated by various groups of investigators in ophthalmology. However, to adequately tackle the ethical and societal challenges associated with the rise of AI in ophthalmology, a more comprehensive approach is preferable. Specifically, AI should be viewed as sociotechnical, meaning this technology shapes, and is shaped by social phenomena.

/pdf/the-ethical-and-societal-considerations-for-the-rise-of-3alfganu.pdf

The Ethical and Societal Considerations for the Rise of Artificial Intelligence and Big Data in Ophthalmology

Does senescence play a role in age-related macular degeneration?

Sleep deprivation (SD) is a global public health burden, and has a detrimental role in the nervous system. Retina is an important part of the central nervous system; however, whether SD affects retinal structures and functions remains largely unknown. Herein, chronic SD mouse model indicated that loss of sleep for 4 months could result in reductions in the visual functions, but without obvious morphologic changes of the retina. Ultrastructural analysis by transmission electron microscope revealed the deterioration of mitochondria, which was accompanied with the decrease of multiple mitochondrial proteins in the retina. Mechanistically, oxidative stress was provoked by chronic SD, which could be ameliorated after rest, and thus restore retinal homeostasis. Moreover, the supplementation of two antioxidants, α-lipoic acid and N-acetyl-l-cysteine, could reduce retinal reactive oxygen species, repair damaged mitochondria, and, as a result, improve the retinal functions. Overall, this work demonstrated the essential roles of sleep in maintaining the integrity and health of the retina. More importantly, it points towards supplementation of antioxidants as an effective intervention strategy for people experiencing sleep shortages. Sleep deprivation (SD) is a global public health burden, and has a detrimental role in the nervous system. Retina is an important part of the central nervous system; however, whether SD affects retinal structures and functions remains largely unknown. Herein, chronic SD mouse model indicated that loss of sleep for 4 months could result in reductions in the visual functions, but without obvious morphologic changes of the retina. Ultrastructural analysis by transmission electron microscope revealed the deterioration of mitochondria, which was accompanied with the decrease of multiple mitochondrial proteins in the retina. Mechanistically, oxidative stress was provoked by chronic SD, which could be ameliorated after rest, and thus restore retinal homeostasis. Moreover, the supplementation of two antioxidants, α-lipoic acid and N-acetyl-l-cysteine, could reduce retinal reactive oxygen species, repair damaged mitochondria, and, as a result, improve the retinal functions. Overall, this work demonstrated the essential roles of sleep in maintaining the integrity and health of the retina. More importantly, it points towards supplementation of antioxidants as an effective intervention strategy for people experiencing sleep shortages. 

Chronic Sleep Deprivation Impairs Visual Functions via Oxidative Damage in Mice.

Background There is accumulating evidence of the associations between age-related eye diseases (AREDs) and smoking or dietary factors. We aimed to provide an umbrella review of the published literature pertaining to smoking or dietary intake as risk factors for major AREDs including cataract, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy. Methods We searched for pertinent systematic reviews or meta-analyses in PubMed and Web of Science until 16 April 2022. We reperformed the meta-analysis of each association using random effects models. The heterogeneity and 95% prediction interval were calculated. The presence of small-study effect or excess significance bias was also assessed. Results In total, 64 associations from 25 meta-analyses and 41 associations from 10 qualitative systematic reviews were evaluated. There was convincing (class I) evidence for only one association, namely current smoking and cataract. Two factors had highly suggestive (class II) evidence, namely ever smoking associated with cataract and fish consumption associated with AMD. We also found suggestive (class III) evidence for associations between the dietary intake of omega-3 polyunsaturated fatty acid, lutein, zeaxanthin, vitamin C and the risk of cataract. Conclusions Smoking as a risk factor for cataract was the most robust association we identified. We also identified several dietary elements associated with AREDs. Large prospective studies are warranted to further examine the associations discussed in this review. PROSPERO registration number CRD42022339082.

Smoking, dietary factors and major age-related eye disorders: an umbrella review of systematic reviews and meta-analyses

Impact of major age-related eye disorders on health-related quality of life assessed by EQ-5D: a systematic review and meta-analysis.

The retinal vessel caliber (RVC) is an important biomarker of cardiovascular diseases, which can be semi-automatically measured by fundus photography. This review investigated the associations between the RVCs and the life styles of early life, such as physical activity (PA), sedentary behavior (SB), dietary and sleep, by summarizing the findings from studies on children and adolescents. Two databases (Medline and Embase) were searched from their inception to 30 June 2022. The selected studies were literatures on observational designs, fundus photographs, retinal vessels and lifestyles of children or adolescents. Correlation coefficients of unhealthy life styles and RVCs were transformed to Fisher’s z-scores, and the random-effects model was applied to pool data. A total of 18 observational studies were selected; the lifestyles accessed include 9 studies for PA and SB, 8 studies for dietary and 1 study for sleep. The meta-analysis on the correlation coefficients of regression models found the high level of SB (qualified by screen time, ST) was associated the narrower central retinal arteriolar equivalent (CRAE) among children (r = −0.043, 95% confidence intervals [CI] −0.078 to −0.009). By comparing the first and fourth quartiles of PA, the meta-analysis showed that more indoor PA was associated with smaller venular calibers and more outdoor PA was associated with wider CRAE (r = 0.88, 95%CI −3.33 to 0). Unhealthy lifestyles might be harmful on the retinal microcirculation among children and adolescents but their health effect seems not to be as significant as those in adults.

/pdf/unhealthy-lifestyles-and-retinal-vessel-calibers-among-29l0gaab.pdf

Unhealthy Lifestyles and Retinal Vessel Calibers among Children and Adolescents: A Systematic Review and Meta-Analysis

Précis: Normal tension glaucoma patients had softer corneas than normal controls, whereas high-tension glaucoma and ocular hypertension patients had stiffer corneas. Purpose: To comprehensively identify the corneal biomechanical differences of patients with primary open angle glaucoma (POAG) and ocular hypertension (OHT) using the Ocular Response Analyzer or the Corvis ST. Methods: The electronic databases PubMed, Embase, and Web of Science were comprehensively searched for studies comparing corneal biomechanical differences between POAG and OHT patients with normal controls by Ocular Response Analyzer or Corvis ST. The weighted mean differences and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed according to the subtypes of POAG, including high-tension glaucoma (HTG) and normal tension glaucoma (NTG). Results: Thirty-one case-control studies were ultimately included, with 2462 POAG patients, 345 OHT patients, and 3281 normal controls. The corneal hysteresis (CH), corneal resistance factor (CRF), and highest concavity time (HC-t) were all lower in POAG patients than in normal controls. The CH, time at the second applanation (A2t), HC-t, highest concavity radius (HC-R), and deformation amplitude at the highest concavity (HC-DA) were lower in OHT patients, while the CRF, time at the first applanation (A1t), and stiffness parameter at the first applanation (SP-A1) were greater in OHT patients than in normal controls. The subgroup analyses showed that the CH, A2t, length at the second applanation (A2L), and HC-DA were lower in HTG, and the CH, CRF, A1t, and HC-t were lower in NTG patients than in normal controls. Conclusion: The corneas of NTG patients are more deformable than normal controls, whereas the corneas of HTG and OHT patients are stiffer.

Corneal Biomechanics in Primary Open Angle Glaucoma and Ocular Hypertension: A Systematic Review and Meta-analysis

BACKGROUND
The objective of this study was to evaluate the comparative efficacy of current interventions for the prevention of retinopathy of prematurity (ROP) in premature infants.


METHODS
A network meta-analysis (NMA) was performed. We searched PubMed, Web of Science, Scopus, Embase, and the Cochrane Library for relevant studies from their inception to May 5, 2022. Publications were eligible for our study if they were randomized controlled trials (RCTs) involving preterm infants at <37 weeks of gestational age and reported the incidence of any-stage ROP treated with the interventions of interest. The overall effect was pooled using the random effects model.


RESULTS
We identified 106 RCTs (involving 23894 participants). This NMA showed that vitamin A supplementation markedly reduced the incidence of ROP, in comparison with placebo (odds ratio [OR] = 0.59, 95% credible interval [95% CrI] 0.33, 0.85), fish oil-based lipid emulsion (OR = 0.57, 95% CrI 0.24, 0.90), early erythropoietin (OR = 0.51, 95% CrI 0.34, 0.98), probiotics (OR = 0.48, 95% CrI 0.32, 0.97), and human milk (OR = 0.50, 95% CrI 0.21, 0.78). Vitamin A supplementation has the highest probability of being the best option for reducing the ROP risk compared with the other 20 interventions based on its surface under the cumulative ranking curve (SUCRA) value (SUCRA = 92.50%, 95% CrI 0.71, 1.00).


CONCLUSIONS
Our findings suggest that among 21 interventions, vitamin A supplementation might be the best method of preventing ROP. This NMA offers an important resource for further efforts to develop preventive strategies for ROP.

/pdf/efficacy-comparison-of-21-interventions-to-prevent-3ne1awxa.pdf

Efficacy comparison of 21 interventions to prevent retinopathy of prematurity: a Bayesian network meta-analysis

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