Macular Degeneration Research Articles

Application of Artificial Intelligence Models to Predict the Onset or Recurrence of Neovascular Age-Related Macular Degeneration

Neovascular age-related macular degeneration (nAMD) is one of the major causes of vision impairment that affect millions of people worldwide. Early detection of nAMD is crucial because, if untreated, it can lead to blindness. Software and algorithms that utilize artificial intelligence (AI) have become valuable tools for early detection, assisting doctors in diagnosing and facilitating differential diagnosis. AI is particularly important for remote or isolated communities, as it allows patients to endure tests and receive rapid initial diagnoses without the necessity of extensive travel and long wait times for medical consultations. Similarly, AI is notable also in big hubs because cutting-edge technologies and networking help and speed processes such as detection, diagnosis, and follow-up times. The automatic detection of retinal changes might be optimized by AI, allowing one to choose the most effective treatment for nAMD. The complex retinal tissue is well-suited for scanning and easily accessible by modern AI-assisted multi-imaging techniques. AI enables us to enhance patient management by effectively evaluating extensive data, facilitating timely diagnosis and long-term prognosis. Novel applications of AI to nAMD have focused on image analysis, specifically for the automated segmentation, extraction, and quantification of imaging-based features included within optical coherence tomography (OCT) pictures. To date, we cannot state that AI could accurately forecast the therapy that would be necessary for a single patient to achieve the best visual outcome. A small number of large datasets with high-quality OCT, lack of data about alternative treatment strategies, and absence of OCT standards are the challenges for the development of AI models for nAMD.

Modified pro re nata regimen of brolucizumab in treatment-naive neovascular age-related macular degeneration.

Purpose- To study the efficacy and safety of pro re nata regimen of brolucizumab, without loading dose, in treatment-naive patients with neovascular age-related macular degeneration (nAMD). Case series- Retrospective, observational study. We included all consecutive patients diagnosed with treatment- naïve nAMD undergoing Brolucizumab in Humanitas eye clinic, Turin, Italy between April 2022 and May 2023. Treatment was performed following pro re nata regimen without loading phase. Injection intervals (time between two injections), adverse events, changes in best corrected visual acuity (BCVA), central macular thickness (CMT), maximal retinal thickness (MRT), intraretinal and subretinal fluid (IRF, SRF) were evaluated descriptively up to one year after the first injection. Twenty-one eyes of 21 patients were included in the study. The mean number of injections was 2.4±0.7 at 3 month, 3.0±2.0 at 6 month, 3.1±2.4 at 9 month and 3.8±2.8 at 12 month, respectively. BCVA significantly improved from 20/80 Snellen (0.6±0.3 LogMar) to 20/50 Snellen (0.4±0.3 LogMar) at month 12 (p = 0.044). CMT and MRT significantly reduced from 426 μm and 606 μm at baseline, to 248 μm and 356 μm at one-year follow-up (p=0.00067 and p=0.02, respectively). SRF and IRF also progressively resolved. On the other hand, intraocular inflammation (IOI) events occurred in 9.5% of cases during follow-up. IOI resolved in all cases with prompt treatment without visual sequelae. Conclusions- In our study, pro re nata regimen of brolucizumab without loading phase appears to be an effective treatment option in treatment-naive nAMD patients, with IOI rate similar to the one reported in trials and lower number of injections.

Reactive Oxygen Species Responsive Supramolecular Prodrug Eyedrops for the Treatment of Choroidal Neovascularization.

Choroidal neovascularization (CNV) represents a hallmark of neovascular fundus diseases, including age-related macular degeneration and diabetic retinopathy. Traditional eyedrops have encountered formidable challenges in treating CNV, primarily due to their extremely poor intraocular bioavailability and potential adverse off-target effects. Herein, an ocular-permeable supramolecular prodrug eyedrop (Di-DAS/P-PCD) has been developed for the on-demand delivery of antiangiogenic agents in the oxidative microenvironment of CNV. The eyedrop nanoformulation is composed of cell-penetrating peptide-modified PEGylated cyclodextrin (P-PCD) and reactive oxygen species (ROS)-sensitive antiangiogenic dasatinib prodrug Di-DAS. In a laser-induced CNV mouse model, daily instillation of Di-DAS/P-PCD has achieved remarkable penetration into the choroid and significantly suppressed CNV growth while exhibiting a good biocompatibility profile. Our results highlight the potential of the supramolecular prodrug eyedrops as a versatile approach for the targeted treatment of CNV and other neovascular eye disorders.

Validation of Inter-Reader Agreement/Consistency for Quantification of Ellipsoid Zone Integrity and Sub-RPE Compartmental Features Across Retinal Diseases.

An unmet need exists when clinically assessing retinal and layer-based features of retinal diseases. Therefore, quantification of retinal-layer-thicknesses/fluid volumes using deep-learning-augmented platforms to reproduce human-obtained clinical measurements is needed. In this analysis, 210 spectral-domain optical coherence tomography (SD-OCT) scans (30 without pathology, 60 dry age-related macular degeneration [AMD], 60 wet AMD, and 60 diabetic macular edema [total 23,625 B-scans]) were included. A fully automated segmentation platform segmented four retinal layers for compartmental assessment (internal limiting membrane, ellipsoid zone [EZ], retinal pigment epithelium [RPE], and Bruch's membrane). Two certified OCT readers independently completed manual segmentation and B-scan level validation of automated segmentation, with segmentation correction when needed (semi-automated). Certified reader metrics were compared to gold standard metrics using intraclass correlation coefficients (ICCs) to assess overall agreement. Across different diseases, several metrics generated from automated segmentations approached or matched human readers performance. Absolute ICCs for retinal mean thickness measurements showed excellent agreement (range 0.980-0.999) across four cohorts. EZ-RPE thickness values and sub-RPE compartment ICCs demonstrated excellent agreement (ranges of 0.953-0.987 and 0.944-0.997, respectively) for full dataset, dry-AMD, and wet-AMD cohorts. Analyses demonstrated high reliability and consistency of segmentation of outer retinal compartmental features using a completely human/manual approach or a semi-automated approach to segmentation. These results support the critical role that measuring features, such as photoreceptor preservation through EZ integrity, in future clinical trials may optimize clinical care.

Targeting the VEGFR2 signaling pathway for angiogenesis and fibrosis regulation in neovascular age-related macular degeneration

Neovascular age-related macular degeneration (nAMD) is characterized by abnormal blood vessel growth from the choroid, leading to complications and eventual blindness. Despite anti-VEGF therapy, subretinal fibrosis remains a major concern, as VEGF/VEGF receptor-2 (VEGFR2) signaling can contribute to both angiogenesis and fibrosis. For the identification of the aqueous humor proteome, we performed liquid chromatography with tandem mass spectrometry analysis. To investigate the potential therapeutic effects of targeting the VEGF signaling pathway using apatinib, a highly selective VEGFR2 tyrosine kinase inhibitor, this study employed in vitro (THP-1 conditioned media-treated ARPE-19 cells) and in vivo (laser-induced choroidal neovascularization mouse) models of nAMD. This study revealed elevated VEGFR2 protein levels in the aqueous humor of nAMD patients, suggesting a potential target to mitigate neovascularization and fibrosis in nAMD. Apatinib effectively reduced VEGFA and αSMA levels in both in vitro and in vivo models. Moreover, apatinib showed improvement in laser-induced subretinal hyper-reflective lesions. The action mechanism was linked to the inhibition of VEGFR2 activation, leading to the suppression of both angiogenesis and fibrosis through the downregulation of STAT3 phosphorylation. Therefore, the VEGFR2 signaling pathway appears to play a central role in the development of nAMD by regulating both angiogenesis and fibrosis.

Association of subretinal drusenoid deposits and cardiovascular disease

The presence of subretinal drusenoid deposits (SDDs) in patients with age-related macular degeneration (AMD) appears to be correlated with cardiovascular disease (CVD) and may serve as a useful tool for predicting certain forms of CVD. Here, we tested this hypothesis by examining whether patients with AMD with SDDs are more likely to have a cardiovascular-related condition and/or undergo a cardiovascular procedure. This is a retrospective cohort study. We included a total of 597 patients with AMD either with SDDs (n = 332) or without SDDs (n = 265). All patients underwent spectral-domain optical coherence tomography (SD-OCT). The SD-OCT scans were annotated by masked, experienced graders. We also extracted data from the patients’ electronic medical records (EMRs), including patient demographics, cardiovascular diagnoses, and CVD-related procedures based on ICD-9 codes. AMD patients with SDDs were more likely to be diagnosed with CVD or undergo a cardiovascular procedure compared to AMD patients without SDDs, particularly percutaneous transluminal coronary angioplasty (PTCA; OR 2.73, 95% CI [1.21, 6.13], p = 0.02). Multivariate analysis confirmed the association between the presence of SDDs and a background of PTCA in the presence of other covariates. These data suggest that the presence of SDDs in patients with AMD correlates with certain severe cardiovascular conditions; SDDs and CVD may share common pathogenic pathways.

Immunocorrective effects of Tricor fenofibrate in the treatment of the early and intermediate stages of age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment, blindness and disability in the elderly. Treatment of end-stage AMD is extremely limited and requires invasive interventions. Currently, there is an active search for remedies aimed at preventing the degenerative process in the retina in the early stages of the disease. AMD is a multifactorial pathology, has common mechanisms with diseases associated with aging, metabolic shifts and hemodynamic disorders. The study of the effects of drugs already used to correct these disorders in the general clinic may also be of interest to ophthalmologists. The aim of the work was to study the dynamics of inflammatory markers of activation of the vascular endothelium and cytokines of the immune response in the tear fluid (TF) of patients with initial and intermediate stages of AMD against the background of the use of Tricor fenofibrate. 65 people were examined, divided into three groups according to the AREDS classification: group I – 20 people with early AMD (AREDS2), group II – 16 patients with intermediate AMD (AREDS3), 29 healthy elderly people without ophthalmopathology entered the age control group (AREDS1 – risk group). Patients of groups I and II received Tricor at a dose of 145 mg once a day for 9 months. Tear fluid (TF) was taken twice: before and immediately after the completion of the course of treatment. The determination of sICAM-1, sVCAM-1, sE-, sP-selectin and MCP-1/CCL2 in CS was performed by flow cytometry using a self-constructed multiplex panel from compatible simplex test kits Human FlowCytomixTM Simplex (Bender MedSystem GmbH, Germany); IL-1β, IL-2 IL-6 TNFα was determined within the framework of the Human Flow CytomixTM 15 Flex system (Bender MedSystem GmbH, Germany). Data processing was performed in the FlowCytomix Pro v 6.0 package (Bender Med Systems GmbH, Germany). According to the results of the study, a significant effect of Tricor fenofibrate was found on the initially high levels of local production of IL-1β, IL-2, IL-6, MCP-1/CCL2 and sICAM-1 in the AREDS2 group, which indicated a direct anti-inflammatory, vasoprotective effect in the treatment of the initial stage of AMD; a similar effect of the drug, but less pronounced, noted in the AREDS3 group. The ophthalmological examination data also indicated stabilization of visual functions and the clinical picture of the fundus, improvement of intraocular blood circulation in patients of the main groups. Thus, the use of Tricor can help prevent the degenerative process in the retina in the early stages of AMD development.

Dry and neovascular "wet" age-related macular degeneration: Upcoming therapies.

The age-related macular degeneration (AMD) field is witnessing promising advancements in therapeutic options. Breakthrough drugs such as pegcetacoplan and avacincaptad have been FDA-approved for dry AMD, marking a significant development as there were no treatment options until August 2023. While several antivascular endothelial growth factor (VEGF) inhibitors have been approved for wet AMD, challenges persist with the need for frequent dosing. New treatments such as gene therapy, cell therapy, WNT pathway agonists, complement inhibitors, and anti-VEGF combination drugs are under development to address these issues. These developments are exciting and hold promise for transforming the field of medicine, offering hope for improved outcomes and enhanced patient care in managing AMD.

Looking beyond the eyes of the patient: The importance of effective communication in the treatment of age-related macular degeneration.

Patients with exudative and nonexudative age-related macular degeneration (AMD) can experience physical, mental, social, administrative or financial burden that are associated with the treatment of this progressive chronic disease. The role of healthcare providers in supporting patients who experience high treatment burden can be important, especially when it comes to effective communication. Despite previous research underlining the need to improve patient-provider communication in AMD care, patient experiences with communication, and how these are related to perceived treatment burden, remain underexplored. A survey was distributed among Dutch patients with AMD, which contained questions on several aspects of communication with the patient's ophthalmologist, such as the Quality Of communication Through the patients' Eyes (QUOTE-COMM, including task-, affect- and therapy-oriented communication) questionnaire. Patients were primarily enlisted through a patient association. A total of 162 patients completed the questionnaire, of which 133 provided fully completed responses. While patients reported positive experiences with affect-oriented communication of their ophthalmologist, they rated task- and therapy-oriented communication as below their expectations. Most patients wished to receive (additional) information on AMD-related costs (71%), future perspectives (71%) and coping with negative emotions pertaining to the disease (68%). Both lower experience scores on task- and affect-oriented communication and lower self-efficacy were associated with higher administrative burden and mental burden among patients. Our study shows that current communication, information provision and decision-making do not fully meet patients' needs and preferences. Enhancing patient-provider communication seems important, as effective dialogue is likely to diminish patients' perceived treatment burden.

Dynamics of clinical and immunological parameters in retinal pigment epithelium transplantation in the context of combined immunosuppressive therapy in the rabbit model of retinal degeneration

Progressive damage of the retinal pigment epithelium (RPE) underlies the pathogenesis of degenerative retinal diseases such as: age-related macular degeneration (AMD), Stargardt’s disease, retinitis pigmentosa, Best’s disease and others. This group of diseases led by AMD leads to irreversible loss of visual functions, blindness and disability. The possibilities of therapy of late stages of AMD are extremely limited. The most promising approach to replace the damaged retinal pigment epithelium appears to be transplantation of RPE cells derived from induced pluripotent stem cells (iPSC-RPE) into the subretinal space (SRS). Despite immune privilege in the SRS, transplantation of xenogeneic cellular material causes severe inflammation in the posterior segment of the eye and leads to graft rejection in an in vivo experiment in the absence of immunosuppression. The solution to the problem of tissue incompatibility in this case can be the use of combined immunosuppressive therapy (CIT), aimed, on the one hand, at suppression of local inflammation (in the eye) and, on the other hand, at suppression of the systemic transplantation immune response. The aim of the study: clinical and immunological analysis of the results of transplantation of IPSC-RPE suspension on the background of CIT, including single intravitreal intraoperative administration of kenalog and further systemic application of mycophenolate mofetil (MMF), in the model of RPE atrophy in rabbits. Standard and specialized ophthalmological examination was performed at early and distant terms after the intervention in order to clinically assess the posttransplantation process. To analyze the immune status, vitreous humor (VH) and blood serum (BS) of rabbits of the experimental groups were collected. The concentrations of TGF-β1, TGF-β2, and IL-2 were determined in the biomaterial using solid-phase enzyme immunoassay. According to the results of the study, subretinal transplantation of IPSC-RPE, performed against the background of combination of single intravitreal intraoperative administration of kenalog and systemic application of MMF, is a safe method, which provides preservation of the retina and other adjacent structures of the eye and allows to prevent rejection of xenogenic material during its transplantation both in a healthy eye and with pre-formed RPE atrophy, which opens perspectives for full testing of biological effects realized by IPSC-RPE.

Caffeine and Vision: Effects on the Eye.

Caffeine, commonly found in coffee and tea, affects various aspects of eye health as it blocks adenosine receptors, impacting tear production, intraocular pressure, macular perfusion, and choroidal thickness. However, its connection with eye conditions like glaucoma and cataracts remains uncertain due to conflicting research findings. Some studies suggest potential benefits for cataracts, while others warn against frequent caffeine intake in glaucoma and surgical scenarios due to possible increases in intraocular pressure. Conflicting evidence also exists regarding its effects on dry eye, macular degeneration, myopia/hyperopia, diabetic retinopathy, retinopathy of prematurity, and central serous retinopathy. Caffeine does not seem to be a risk factor for dry eye, although studies have shown that caffeine may offer protection against wet age-related macular degeneration, and the metabolite 7-methylxanthine could be a more promising treatment for myopia. Moreover, caffeine can potentially cause tremors and might hinder surgical performance, especially in less experienced surgeons. Recommendations from experts vary, highlighting the need for further research to fully understand how caffeine affects the eye. Individuals genetically predisposed to glaucoma should be cautious due to the possibility of clinically significant elevations in intraocular pressure with caffeine consumption. For delicate procedures like microsurgery, where tremors can be detrimental, caution should be exercised with caffeine. This review underscores the importance of additional studies to provide clearer insights and prudent recommendations regarding caffeine's impact on eye health.

Ginsenoside Rg3 Improved Age-Related Macular Degeneration Through Inhibiting ROS-Mediated Mitochondrion-Dependent Apoptosis In Vivo and In Vitro.

Age-related macular degeneration (AMD) is marked by a progressive loss of central vision and is the third leading cause of irreversible blindness worldwide. The exact mechanisms driving the progression of this macular degenerative condition remain elusive, and as of now, there are no available preventative measures for dry AMD. According to ancient records, ginseng affects the eyes by brightening them and enhancing wisdom. Modern pharmacological research shows that the active ingredients in ginseng, ginsenosides, may be used to prevent or improve eye diseases that threaten vision. Some articles have reported that ginsenoside Rg3 can treat diabetic retinopathy in mice, but no reports exist on its effects and mechanisms in AMD. Therefore, the role and mechanism of ginsenoside Rg3 in AMD warrant further study. This study aims to investigate the effects of Rg3 on AMD and its underlying molecular mechanisms. We established a mouse model of AMD to examine the impact of ginsenoside Rg3 on NaIO3-induced apoptosis in the retina and to explore the related intrinsic mechanisms. The in vivo results indicated that ginsenoside Rg3 prevents NaIO3-induced apoptosis in retinal pigment epithelial cells by inhibiting reactive oxygen species production and preventing the reduction in mitochondrial membrane potential. Additionally, we assessed the levels of protein expression within the apoptosis pathway. Ginsenoside Rg3 decreased the expression of Bax, cleaved caspase-3, and cleaved caspase-9 proteins. Additionally, it increased the expression of Bcl-2 by decreasing P-JNK levels. Moreover, our in vivo results showed that ginsenoside Rg3 enhanced retinal structure, increased the relative thickness of the retina, and decreased the extent of disorganization in both the inner and outer nuclear layers. Ginsenoside Rg3 may safeguard the retina against NaIO3-induced cell apoptosis by attenuating reactive-oxygen-species-mediated mitochondrial dysfunction, in which the JNK signaling pathway is also involved. These findings suggest that ginsenoside Rg3 has the potential to prevent or attenuate the progression of AMD and other retinal pathologies associated with NaIO3-mediated apoptosis.

Curcuma-Based Nutritional Supplements and Risk of Age-Related Macular Degeneration

Curcuma-based nutritional supplements (CBNS) are natural anti-inflammatory and antioxidant agents that may confer benefits against age-related macular degeneration (AMD). To examine the association between the use of CBNS and the risk of development or progression of AMD. This was a retrospective cohort study with data collection in June of 2024. Data were gathered from the aggregated electronic health records research network, TriNetX (Cambridge, Massachusetts). Patients without AMD were included in the study before propensity score matching (PSM); these included those taking and not taking CBNS. Patients with no history of AMD were stratified by instances of CBNS prescription records. Patients with a history of early nonexudative AMD stratified by instances of CBNS prescription records were also identified. PSM was performed to control for baseline demographics and medical comorbidities. Patients were stratified by whether or not they were taking CBNS using RxNorm (National Library of Medicine) codes. Relative risk (RR) of developing nonexudative AMD, exudative AMD, advanced nonexudative AMD or geographic atrophy (GA), blindness, or requiring intravitreal anti-vascular endothelial growth factor (VEGF) therapy. A total of 66 804 patients (mean [SD] age, 64.9 [10.1] years; 44 124 female [66.1%]) taking CBNS and 1 809 440 patients (mean [SD] age, 67.0 [9.5] years; 999 534 female [55.2%]) not taking CBNS were included in this study. Among patients without a history of AMD aged 50 years or older, CBNS use was associated with lower rates of developing nonexudative AMD (RR, 0.23; 95% CI, 0.21-0.26; P < .001), advanced nonexudative AMD or GA (RR, 0.11; 95% CI, 0.07-0.17; P < .001), exudative AMD (RR, 0.28; 95% CI, 0.24-0.32; P < .001), blindness (RR, 0.46; 95% CI, 0.36-0.59; P < .001), or requiring intravitreal anti-VEGF therapy (RR, 0.15; 95% CI, 0.13-0.17; P < .001) when compared with matched patients not taking CBNS. Results were consistent among subsets of patients 60 and 70 years or older, respectively. Among patients with early nonexudative AMD, subsequent instances of CBNS prescription records were associated with lower rates of developing advanced nonexudative AMD or GA (RR, 0.58; 95% CI, 0.41-0.81; P < .001) when compared with matched patients with early nonexudative AMD without a CBNS prescription record. Results of this cohort study suggest that a reduced risk of developing AMD or progression to later stages of AMD was associated with subsequent use of CBNS. Further investigation to validate these findings, safety, and potential pharmacoprotective mechanisms of CBNS in AMD are suggested.

Selected Trace Elements and Their Impact on Redox Homeostasis in Eye Health

Oxidative stress plays a crucial role in the pathogenesis of various ocular degenerative diseases, leading to structural and functional changes in eye tissues. This imbalance between reactive oxygen species (ROS) and antioxidants significantly contributes to conditions such as age-related macular degeneration, diabetic retinopathy, cataracts, and glaucoma. Both enzymatic and nonenzymatic antioxidants are vital for maintaining ocular health by neutralizing ROS and restoring cellular redox balance. Essential trace elements, including iron, zinc, copper, and selenium, are fundamental for the proper functioning of these antioxidant systems. Iron is indispensable for enzymatic activity and cellular energy production, zinc supports numerous proteins involved in visual functions and antioxidant defense, copper is essential for various enzymatic reactions preventing oxidative stress, and selenium is critical for the activity of antioxidant enzymes such as glutathione peroxidase (GPX) and thioredoxin reductase (TrxR). This review summarizes current research on the complex interactions between oxidative stress and trace elements in ocular diseases, highlighting the therapeutic potential of antioxidant supplementation to mitigate oxidative damage and improve eye health. By integrating insights from studies on oxidative stress, trace elements, and eye physiology, this article underscores new diagnostic and therapeutic strategies that could lead to more effective prevention and treatment of ocular diseases, aiming to enhance clinical outcomes and guide future research in optimizing therapeutic strategies for eye health.

Geographic atrophy progression secondary to age-related macular degeneration: Five years of follow-up.

To study the progression of geographic atrophy (GA) secondary to age-related macular degeneration over a five-year follow-up. Eyes with GA included to assess demographic data, yearly optical coherence tomography (OCT) findings and the GA growth rate on infra-red (IR) images. A total of 41 eyes of 29 patients were included with a mean age of 81.76 ± 6.37 at baseline, and 65.51% were females. Over five years, there was a significant increase in the mean GA area from 8.44 ± 8.98 mm² to 13.32 ± 10.07 mm² (P < 0.001), with an annual growth rate of 1.14 ± 0.78 mm². The annual growth rates in females were slightly higher compared to males (1.29 ± 0.89 mm2 vs 0.96 ± 0.49 mm2, p = 0.569), and in smokers was slightly higher than non-smokers (1.35 ± 0.85 mm2 vs 0.94 ± 0.66 mm2, p = 0.100). Larger GA areas at the baseline showed higher GA progression in mm2 per year (P = 0.04). Smaller GA areas and fovea-spared GA at the baseline exhibited a larger percentage increase (P < 0.001 and P = 0.015, respectively). There was a lower GA progression rate in eyes with outer retinal tubulations (ORT) (P = 0.027), yet no significant correlation was found between GA progression and other OCT features. Smaller, fovea-sparing GA eyes experienced a more substantial proportional increase over five years. Also, The presence of ORT was associated with a slower rate of GA progression. Additionally, we observed a trend of faster GA growth in smokers and female genders.

Multiple retinal vein thrombi after an intravitreal aflibercept 8 mg injection for age-related macular degeneration.

Multiple retinal vein thrombi after an intravitreal aflibercept 8 mg injection for age-related macular degeneration.

The gut-eye axis: from brain neurodegenerative diseases to age-related macular degeneration.

Age-related macular degeneration Is a serious neurodegenerativo disease of the retina that significantly impacts vision. Unfortunately, the specific pathogenesis remains unclear, and effective early treatment options are consequently lacking. The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host. The intestinal microbiome undergoes dynamic changes owing to age, diet, genetics, and other factors. Such dysregulation of the intestinal flora can disrupt the microecological balance, resulting in immunological and metabolic dysfunction in the host, and affecting the development of many diseases. In recent decades, significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract, including the brain. Indeed, several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Similarly, the role of the "gut-eye axis" has been confirmed to play a role in the pathogenesis of many ocular disorders. Moreover, age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies. As such, the intestinal flora may play an important role in age-related macular degeneration. Given the above context, the present review aims to clarify the gut-brain and gut-eye connections, assess the effect of intestinal flora and metabolites on age-related macular degeneration, and identify potential diagnostic markers and therapeutic strategies. Currently, direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited, while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration. Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions, while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.

Global, regional, and national burden of age-related macular degeneration, 1990-2019: an age-period-cohort analysis based on the Global Burden of Disease 2019 Study.

This study aimed to explore the burden of disease and disparities in age-related macular degeneration (AMD) at the global, regional, and national levels from 1990 to 2019 using data from the Global Burden of Disease (GBD) 2019 study, with a particular focus on associations with age, period, and cohort. We derived disability-adjusted life years (DALYs) and age-standardized rates of AMD from the GBD 2019. We used an age-period-cohort (APC) model to estimate the overall annual percentage changes in DALYs (net drifts), the annual percentage changes in different age groups (local drifts), the longitudinal age profiles (longitudinal age-specific rates), and the relative risks of period and cohort (period and cohort effects) between 1990 and 2019. Further analysis was conducted by country, region, gender and sociodemographic index (SDI). Globally, the number of DALYs increased from 296771.9321 (95% uncertainty interval [UI], 205462.8041-418699.8184) in 1990 to 564055.0967 (95% UI, 392930.6967-789194.6407) in 2019 (59.7% were female), while the age-standardized DALYs rates decreased from 8.29 per 100,000 (95% UI, 5.8-11.58/100,000) to 7.05 per 100,000 (95% UI, 4.92-9.84/100,000). With increasing age, the burden of AMD increased, and the DALYs rates in female was greater than that in male in all age groups. The burden of disease varied across SDI regions and countries. The top three countries in terms of the number of DALYs were China, India and Italy, accounting for 45% of the global total. The burden of AMD varied according to SDI, country, and sex from 1990 to 2019. Due to global population growth and aging, AMD will continue to be a major public health problem in the future, and relevant health policies need to be continuously improved and optimized.

Predictive factors for Submacular Hemorrhage in Age-related Macular Degeneration: A Retrospective Study.

Little is known about the major risk factors for submacular hemorrhage (SMH). This study aimed to evaluate the factors associated with SMH in patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) receiving three consecutive loading doses of intravitreal aflibercept or ranibizumab injections. This retrospective cross-sectional study included 48 patients diagnosed with wAMD and PCV who completed three loading doses under a treat-and-extend regimen. Patients were divided into the SMH group (n=24) and the non-SMH group (age- and sex-matched without SMH). Intravitreal injections, agents, and optical coherence tomography (OCT) features were compared. In the SMH group, SMH occurred approximately 3.29 years after post-nAMD diagnosis. The non-SMH group received more intravitreal injections of aflibercept and brolucizumab during the follow-up period after the initial loading phase. The SMH group exhibited a higher prevalence of serous/hemorrhagic pigment epithelial detachments (PEDs) at the last visit before SMH occurrence compared to the non-SMH group. Patients with a PED increase in the past two visits showed a higher tendency in the SMH group. No other OCT features significantly correlated with SMH development. The presence of serous/hemorrhagic PEDs may indicate a higher risk of SMH, and eyes with these features should be closely monitored to prevent sudden and devastating visual loss caused by SMH.

Application of Artificial Intelligence in the Diagnosis, Follow-Up and Prediction of Treatment of Ophthalmic Diseases.

To describe the application of artificial intelligence (AI) in ophthalmic diseases and its possible future directions. A retrospective review of the literature from PubMed, Web of Science, and Embase databases (2019-2024). AI assists in cataract diagnosis, classification, preoperative lens calculation, surgical risk, postoperative vision prediction, and follow-up. For glaucoma, AI enhances early diagnosis, progression prediction, and surgical risk assessment. It detects diabetic retinopathy early and predicts treatment effects for diabetic macular edema. AI analyzes fundus images for age-related macular degeneration (AMD) diagnosis and risk prediction. Additionally, AI quantifies and grades vitreous opacities in uveitis. For retinopathy of prematurity, AI facilitates disease classification, predicting disease occurrence and severity. Recently, AI also predicts systemic diseases by analyzing fundus vascular changes. AI has been extensively used in diagnosing, following up, and predicting treatment outcomes for common blinding eye diseases. In addition, it also has a unique role in the prediction of systemic diseases.