Severe Visual Loss Research Articles

Visual outcomes and prognostic factors in ischaemic retinal vasculitis

PurposeOur aim was to describe the visual outcomes and determine the clinical factors in ischaemic retinal vasculitis (IRV) that were predictive of a poor visual prognosis or infectious aetiology.MethodsRetrospective cohort...

Feasibility of in-home monitoring for people with glaucoma: the I-TRAC mixed-methods study.

Glaucoma is a chronic disease of the optic nerve and a leading cause of severe visual loss in the UK. Once patients have been diagnosed, they need regular monitoring at hospital eye services. Recent advances in technology mean patients with glaucoma can now monitor their disease at home. This could be more convenient for patients and potentially reduce costs and increase capacity for the NHS. However, it is uncertain whether self-monitoring would be acceptable or possible for patients with glaucoma. The objectives were to: identify which patients are most appropriate for home monitoring; understand views of key stakeholders (patients, clinicians, researchers) on whether home glaucoma monitoring is feasible and acceptable; develop a conceptual framework for the economic evaluation of home glaucoma monitoring; and explore the need for and provide evidence on the design of a future study to evaluate the clinical and cost-effectiveness of digital technologies for home monitoring of glaucoma. In-home Tracking of glaucoma: Reliability, Acceptability, and Cost (I-TRAC) was a multiphase mixed-methods feasibility study with key components informed by theoretical and conceptual frameworks. Expert glaucoma specialists in the UK recruited through professional glaucoma societies; study site staff and patient participants recruited through three UK hospital eye services (England, Scotland, Northern Ireland); and UK research teams recruited though existing networks. Home tonometer that measures intraocular pressure and a tablet computer with a visual function application. Patients were asked to use the technology weekly for 12 weeks. Forty-two patients were recruited. Retention and completion of follow-up procedures was successful, with 95% (n = 40) completing the 3-month follow-up clinic visits. Adherence to the interventions was generally high [adherence to both devices (i.e. ≥80% adherence) was 55%]. Overall, patients and healthcare professionals were cautiously optimistic about the acceptability of digital technologies for home monitoring of patients with glaucoma. While most clinicians were supportive of the potential advantages glaucoma home monitoring could offer, concerns about the technologies (e.g. reliability and potential to miss disease progression) and how they would fit into routine care need to be addressed. Additionally, clarity is required on defining the ideal population for this intervention. Plans for how to evaluate value for money in a future study were also identified. However, the study also highlighted several unknowns relating to core components of a future evaluative study that require addressing before progression to a definitive effectiveness trial. The main limitation relates to our sample and its generalisability, for example, the over-representation of educated persons of white ethnicity who were generally experienced with technology and research motivated. The In-home Tracking of glaucoma: Reliability, Acceptability, and Cost study has demonstrated 'cautious optimism' when considering patients' and healthcare professionals' views on the acceptability of digital technologies for home monitoring of patients with glaucoma. However, the study also highlighted several unknowns relating to the research question and design of a future evaluative study that require addressing before progression to a randomised controlled trial. Further research is required to determine the appropriate population (i.e. low vs. high risk of progression) and further refine the intervention components and delivery for planning of future evaluation studies. This study is registered as Research Registry #6213. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR129248) and is published in full in Health Technology Assessment; Vol. 28, No. 44. See the NIHR Funding and Awards website for further award information.

Automated early detection of acute retinal necrosis from ultra-widefield color fundus photography using deep learning

BackgroundAcute retinal necrosis (ARN) is a relatively rare but highly damaging and potentially sight-threatening type of uveitis caused by infection with the human herpesvirus. Without timely diagnosis and appropriate treatment, ARN can lead to severe vision loss. We aimed to develop a deep learning framework to distinguish ARN from other types of intermediate, posterior, and panuveitis using ultra-widefield color fundus photography (UWFCFP).MethodsWe conducted a two-center retrospective discovery and validation study to develop and validate a deep learning model called DeepDrARN for automatic uveitis detection and differentiation of ARN from other uveitis types using 11,508 UWFCFPs from 1,112 participants. Model performance was evaluated with the area under the receiver operating characteristic curve (AUROC), the area under the precision and recall curves (AUPR), sensitivity and specificity, and compared with seven ophthalmologists.ResultsDeepDrARN for uveitis screening achieved an AUROC of 0.996 (95% CI: 0.994–0.999) in the internal validation cohort and demonstrated good generalizability with an AUROC of 0.973 (95% CI: 0.956–0.990) in the external validation cohort. DeepDrARN also demonstrated excellent predictive ability in distinguishing ARN from other types of uveitis with AUROCs of 0.960 (95% CI: 0.943–0.977) and 0.971 (95% CI: 0.956–0.986) in the internal and external validation cohorts. DeepDrARN was also tested in the differentiation of ARN, non-ARN uveitis (NAU) and normal subjects, with sensitivities of 88.9% and 78.7% and specificities of 93.8% and 89.1% in the internal and external validation cohorts, respectively. The performance of DeepDrARN is comparable to that of ophthalmologists and even exceeds the average accuracy of seven ophthalmologists, showing an improvement of 6.57% in uveitis screening and 11.14% in ARN identification.ConclusionsOur study demonstrates the feasibility of deep learning algorithms in enabling early detection, reducing treatment delays, and improving outcomes for ARN patients.

Pupil Unleashed: Unraveling the Enigma of an Unusual Traumatic Head Injury: A Case Report.

Isolated oculomotor nerve palsy after mild traumatic brain injury is unusual and prognostically significant due to unclear mechanisms and recovery challenges. We present a case of isolated oculomotor nerve palsy following minor head trauma, shedding light on this unusual occurrence. A 24-year-old male experienced severe vision loss and right-sided oculomotor nerve palsy after a motor vehicle collision. Initial imaging showed a hemorrhagic focus in the left posterior fossa and a contusion in the corpus callosum, yet no direct cause for the nerve palsy was found. Partial recovery was observed after 12 months. This case underscores the importance of maintaining a heightened suspicion for occult intracranial findings, especially when the initial non-contrast computed tomography was inconclusive. Timely clinical assessment and appropriate radiological investigations by emergency physicians are crucial for improving the prognosis.

CircSlc17a5 controlled by VLDLR/QKI pathway regulated the choroidal angiogenesis

RationaleVery-low-density lipoprotein receptor (VLDLR) involves in ocular neovascularization, a major cause of severe vision loss. However, the underlying molecular mechanisms were not completely clarified. Here, we aimed to investigate roles of circular RNAs (circRNAs) in VLDLR-associated ocular neovascularization. MethodsVldlr knockout (Vldlr-/-, ko), Robo4 knockout (Robo4-/-, ko) and wild-type (WT) mice were used. Mouse model of oxygen induced retinopathy (OIR) and high-throughput sequence were performed to profile the differential expression of circRNA and transcripts. RNase R treatment, Sanger PCR sequencing and quantitative polymerase chain reaction (qPCR) were used to validate candidate circRNAs and their expression patterns. Choroidal sprouting assay ex vivo and laser induction choroid neovascularization were used to determine the expression and functions of QKI/CircSlc17a5 on choroidal neovascularization. ResultsIn macrophage and ocular tissues derived from Vldlr (Vldlr-/-,Vldlr ko) or Robo4 (Robo4-/-,Robo4 ko) deficiency as well as wild-type (WT) mice, Quaking (Qki) expression was significantly down-regulated in Vldlr deficiency compared to WT and Robo4 deficiency groups. Ectopic VLDLR expression or Reelin stimulation increased expression of QKI in bEnd.3 cells. Circular RNA sequencing uncovered that VLDLR regulated the biogenesis of certain circular RNAs, including the circSlc17a5. The number of Circular RNAs increased in mice treated with OIR. QKI mediated the biogenesis of circSlc17a5, which was an important regulator of choroidal angiogenesis. ConclusionCircSlc17a5 regulated by VLDLR/QKI plays important roles in the choroidal angiogenesis.

Ocular hypertension after EyeCee One preload lens implantation: a retrospective cohort study.

In 2022, several cases of ocular hypertension (OHT) related to EyeCee One preloaded IOLs were reported. The aim of this study was to determine the presurgical and surgical variables associated with this response. An analysis was conducted on patients who underwent isolated cataract surgery between September 2022 and December 2022 at the Hospital Universitario del Henares. The influence of potential factors was studied using the Kruskal-Wallis test and multiple regression analysis. A total of 353 cataract surgeries were included in the study. No significant differences between the different IOLs were found related to a change in the IOP on the first postoperative day (p = 0.395), but the change in the IOP after 1 month was higher in the EyeCee One group (p = 0.016). Approximately 6.1% of the patients who received EyeCee One had an IOP increase greater than 10 mmHg, compared to only 0.8% of the patients who received other IOLs. The odds ratio (OR) of experiencing an IOP increase greater than 10 mmHg in the EyeCee One group at the 1-month visit was 7.99 (1.52-41.99). The multiple regression analysis showed that receiving the EyeCee One lens was associated with a 2-mmHg increase in IOP. A previous history of glaucoma or OHT was not associated with greater IOP. Two patients in the EyeCee One group developed severe visual loss. Patients who received the EyeCee One IOL experienced significant increases in IOP at the 1-month visit. A small number of patients might suffer visual loss secondary to the rise in IOP.

Evaluating therapeutic potential of NR2E3 doses in the rd7 mouse model of retinal degeneration

Retinitis Pigmentosa is a leading cause of severe vision loss. Retinitis Pigmentosa can present with a broad range of phenotypes impacted by disease age of onset, severity, and progression. This variation is influenced both by different gene mutations as well as unique variants within the same gene. Mutations in the nuclear hormone receptor 2 family e, member 3 are associated with several forms of retinal degeneration, including Retinitis Pigmentosa. In our previous studies we demonstrated that subretinal administration of one Nr2e3 dose attenuated retinal degeneration in rd7 mice for at least 3 months. Here we expand the studies to evaluate the efficacy and longitudinal impact of the NR2E3 therapeutic by examining three different doses administered at early or intermediate stages of retinal degeneration in the rd7 mice. Our study revealed retinal morphology was significantly improved 6 months post for all doses in the early-stage treatment groups and for the low and mid doses in the intermediate stage treatment groups. Similarly, photoreceptor function was significantly improved in the early stage for all doses and intermediate stage low and mid dose groups 6 months post treatment. This study demonstrated efficacy in multiple doses of NR2E3 therapy.

Wipe-Out following Gonioscopy-Assisted Transluminal Trabeculotomy combined with Phacoemulsification.

Précis: We report a case of a 62-year-old male patient who developed a wipe-out phenomenon after uncomplicated gonioscopy-assisted transluminal trabeculotomy combined with cataract surgery. A 62-year-old male patient with a diagnosis of pseudo-exfoliation and open-angle glaucoma underwent uncomplicated gonioscopy-assisted transluminal trabeculotomy (GATT) combined with phacoemulsification surgery due to advanced glaucomatous damage and high intraocular pressure. Postoperative decrease in visual acuity and central visual field deterioration suggested a wipe-out phenomenon. Although the wipe-out phenomenon has been reported after other surgeries in patients with advanced glaucoma, as far as we know, this is the first report of a wipe-out phenomenon secondary to GATT combined with phacoemulsification surgery. This complication, which can lead to severe vision loss, should be considered before the surgical decision.

Clinical characteristics of acute macular neuroretinopathy in China associated with COVID-19 infection

Objective: To investigate the clinical features of acute macular neuroretinopathy (AMN) following coronavirus disease 2019 (COVID-19). Methods: This retrospective case series study included 15 patients (28 eyes) diagnosed with AMN at the Department of Ophthalmology, Peking University Third Hospital, from November 2022 to January 2023. The AMN group comprised 4 males and 11 females, with a mean age of (31.36±8.08) years. A control group of 15 individuals [5 males, 10 females; mean age (33.20±5.10) years] who had COVID-19 but did not develop AMN was also included. Data collected for all patients included best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fluorescein fundus angiography (FFA), and optical coherence tomography (OCT) results. Serum cytokine levels, including interleukins (ILs), interferons (IFNs), and tumor necrosis factor-alpha (TNF-α), were measured for both groups. Results: Among the 28 eyes, severe vision loss (BCVA≤0.3) was observed in 3 eyes (10.7%), moderate vision loss (BCVA>0.3 and≤0.5) in 2 eyes (13.3%), and mild vision loss (BCVA>0.5 and≤1.0) in 23 eyes (82.1%). OCT findings in all 28 eyes revealed hyperreflectivity of the outer nuclear layer and disruption of outer retinal structure. Additionally, 3 eyes (10.7%) exhibited cotton wool spots in the posterior pole, 2 eyes (7.1%) showed mild cystoid macular edema with intraretinal hyperreflective dots, and 1 eye (3.6%) presented with paracentral acute middle maculopathy. FFA indicated retinal vasculitis in 2 cases (4 eyes, 14.3%). Serum levels of IL-4, IL-5, IFN-α, and IFN-γ were significantly higher in the AMN group compared to the control group: IL-4 [4.49 (3.66, 6.08) vs. 1.40 (0.62, 1.68) pg/ml], IL-5 [7.34 (5.04, 14.06) vs. 0.17 (0.11, 1.86) pg/ml], IFN-α [8.42 (6.31, 14.89) vs. 0.50 (0.30, 0.83) pg/ml], and IFN-γ [17.93 (12.75, 32.44) vs. 7.43 (0.00, 14.74) pg/ml], with all differences being statistically significant (all P<0.05). Conclusion: AMN following COVID-19 can present with wedge-shaped dark red lesions in the macular area, often accompanied by cotton wool spots and retinal vasculitis. Additionally, there is a significant elevation in various inflammatory cytokines in the serum.

A Review on Diabetic Retinopathy.

Diabetic retinopathy is a well-recognised microvascular complication of diabetes and is among the leading cause of blindness all over the world. Over the last decade, there have been advances in the diagnosis of diabetic retinopathy and diabetic macular edema. At the same time, newer therapies for the management of diabetic retinopathy have evolved. As a result of these advances, a decline in severe vision loss due to diabetes has been witnessed in some developing countries. However, there is a steady increase in the number of people affected with diabetes, and is expected to rise further in the coming years. Therefore, it is prudent to identify diabetic retinopathy, and timely intervention is needed to decrease the burden of severe vision loss. An effort has been made to review all the existing knowledge regarding diabetic retinopathy in this article and summarize the present treatment options for diabetic retinopathy.

Early versus late initiation of infliximab for refractory uveitis in a cohort of Egyptian BD patients

Introduction Behçet’s syndrome is a multisystem inflammatory disease characterized by recurrent oral aphthous ulcers, genital ulcers, skin lesions, and uveitis. Ocular involvement, occurring roughly in 50% of patients, is one of the most feared complications of Behçet’s syndrome. Recurrent severe uveitis leads to irreversible severe vision loss. Purpose The main goals in the management of patients with Behçet’s uveitis are rapid resolution of intraocular inflammation, prevention of recurrent attacks, and achievement of complete remission and preservation of vision. Corticosteroids are generally used for the treatment of acute episodes of inflammation. According to the updated EULAR recommendations for the management of BS ‘any patient with BS and inflammatory eye disease affecting the posterior segment should be on a treatment regime such as azathioprine, cyclosporine-A, interferon alpha or monoclonal tumor necrosis factor alpha antagonists. Methods Infliximab has been increasingly used in the treatment of Behçet’s syndrome patients with uveitis when they are refractory to conventional immunosuppressive therapy. However, there is no consensus on the best time to start anti- tumor necrosis factor alpha therapy. In our study we evaluated the outcome of early initiation of infliximab for refractory uveitis in cohort of Egyptian Behçet’s syndrome patients. Conclusion Early administration of Intravenous Infliximab therapy for severe sight-threatening uveitis and chorioretinitis in Egyptian Behçet’s syndrome patients has a favorable value regarding BCVA. Multidisciplinary approach in managing Behçet’s uveitis is mandatory to reach better functional visual outcome.

A novel surgical technique for macular manipulation in highly myopic eyes with long axial length

Purpose: We developed a novel surgical technique tailored for highly myopic eyes characterized by extended axial lengths. Myopic eyes are prone to macular complications including macular schisis, full-thickness macular holes, and retinal detachment, which can cause severe vision loss. A pars plana vitrectomy is necessary in these cases. However, due to the considerable distance between the posterior pole and the cannula, regular forceps cannot reach the macula in some cases. To overcome this, we inserted a trocar more posteriorly after localizing the ora serrata. Methods: First, we placed two ports and performed partial vitrectomy without the infusion of balanced salt solution (BSS) to reduce the intraocular pressure. Subsequently, we observed the peripheral retina localized to the ora serrata by scleral indentation using forceps. Following the precise marking of the area, a third trocar was inserted and its position and placement confirmed intraoperatively. Results: Surgical maneuvers including a removal of the internal limiting membrane were safely performed using regular forceps through the posteriorly located cannula. Conclusions: The described technique offers a solution to the challenges posed by the extended axial lengths of highly myopic eyes during vitreoretinal surgery. By inserting the trocar more posteriorly, surgeons can enhance accessibility to the macula without requiring specialized equipment or extensive maneuvers.

Update on “Cell Therapy” Clinics Offering Treatments of Ocular Conditions Using Direct-To-Consumer Marketing Websites in the U.S.

To assess the scope of U.S.-based companies advertising and administering non-Federal Drug Administration (FDA) approved cell-based therapy (herein called NFACT) for ocular conditions based on information from companies' public websites after the FDA's legal actions against specific NFACT clinics in 2018 and 2019. Current findings are compared to previously published data from 2017. Trend study looking at U.S.-based companies that use direct-to-consumer marketing and have websites advertising therapy for ocular conditions. A systematic and extensive keyword-based Internet search was utilized to identify, document, and analyze U.S. business websites offering NFACT for ocular conditions as of August 2022. Main outcomes measured include, clinic locations, marketed ocular conditions, types of NFACT offered, source of stem cells used, routes of administration, and treatment costs. From the prior analysis in 2017 to the 2019 analysis, there was a decrease in the number of NFACT clinics from 76 to 62 and companies from 40 to 39. Given the concerning persistence of NFACTs in August 2019 an additional analysis was performed in 2022 which showed a drastic decrease in NFACT clinics from 62 in 2019 to 18 in 2023 and from 39 companies to 13 in 2023. In both 2019 and 2022, the most commonly referenced ocular condition was age-related macular degeneration (2019 - 72%, 2022 - 92%). The state with the most clinics was in Texas (2019 - 12; 2022 - 5). Autologous adipose-derived stem cells were the most common cell type used in both analyses. In 2019 U.S.-based direct-to-consumer companies marketing NFACT persisted despite (1) a lack of high-quality clinical evidence supporting the efficacy of these procedures, (2) the association of some of these treatments with severe vision loss, and (3) increasing FDA oversight and recent legal action. In 2022 the number of clinics and companies decreased, but their persistence is a reminder that continued concern is necessary and ophthalmic associations need to continue advocacy efforts to protect patients from these potentially predatory organizations.

Parallel Analysis of Exosomes and Cytokines in Aqueous Humor Samples to Evaluate Biomarkers for Glaucoma.

Recent emerging studies have demonstrated numerous critical roles of exosomes in cell-to-cell signaling. We investigated exosomes in the aqueous humor of glaucoma patients and controls and compared their characteristics with other biomarkers such as cytokines. Glaucoma patients exhibited higher exosome particle counts and smaller sizes compared to controls. Higher exosome density was correlated with more severe visual field loss. Conversely, concentrations of aqueous humor cytokines, particularly PD-L1, were primarily associated with intraocular pressure, and none of the cytokines showed a significant association with visual field damage. This may reflect the characteristics of exosomes, which are advantageous for crossing various biological barriers. Exosomes may contain more information about glaucoma functional damage occurring in the retina or optic nerve head. This highlights the potential importance of exosomes as signaling mediators distinct from other existing molecules.

Novel Approaches to the Treatment of Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension (IIH) typically affects women of childbearing age, is associated with recent weight gain, and can result in debilitating headache as well as papilledema that can cause vision loss. There have been advances in the medical and surgical treatment of affected patients with IIH that can improve outcomes and tolerability of therapy. Medical treatment with agents that lower intracranial pressure through pathways other than carbonic anhydrase inhibition are being developed, and medically-directed weight loss as well as bariatric surgery now may be considered as primary therapy. New surgical options including venous sinus stenting have shown efficacy even with cases of severe vision loss. Our treatment options for IIH patients are becoming more diverse, and individualized treatment decisions are now possible to address specific components of the patient's disease manifestations and to lead to IIH remission.

A Single-Center Case Series of Acute Retinal Necrosis at Teikyo University: Clinical Characteristics and Treatment Outcomes.

Aim To evaluate the clinical characteristics, treatment course, and prognosis of patients with acute retinal necrosis (ARN), which can rapidly progress and cause severe vision loss. Design Single-center retrospective case series. Subjects and methods Six patients and seven eyes diagnosed with ARN at Teikyo University Hospital were included in this study. The clinical presentation and treatment prognosis were investigated based on data obtained from medical records. Results The mean age of the patients at the initial diagnosis was 63.6 years. Although the mean Logarithm of the Minimum Angle of Resolution (LogMAR) visual acuity tended to decrease from 0.77 at the first visit to 1.29 at the last visit, the difference was not statistically significant. Intraocular manifestations observed during the study period included ocular hypertension (14.3%), anterior uveitis (100.0%), retinal hemorrhage (71.4%), vitreous opacity (100.0%), retinal exudative vasculitis (85.7%), optic nerve atrophy (85.7%), retinal vascular occlusion (85.7%), choroidal atrophy (85.7%), macular edema (100.0%), subretinal fluid in the macula (71.4%), and retinal detachment (85.7%). Treatment modalities included oral and intravitreal antivirals (85.7%), antiplatelet medications (85.7%), steroid eye drops (85.7%), subcapsular (57.1%) and vitreous (42.9%) steroid injections, oral steroids (71.4%), and surgical intervention (85.7%). Vitrectomy led to retinal recovery in all five eyes that underwent the procedure. Conclusions The visual prognosis of patients with ARN is poor, particularly in those with preexisting visual impairment. Early detection coupled with antiviral therapy and prompt surgical intervention have been identified as potential factors that influence visual outcomes. Given the severity of ARN, collecting data from multiple centers could aid in devising future diagnostic and therapeutic strategies.

Metabolic Regulation of Endothelial Cells: A New Era for Treating Wet Age-Related Macular Degeneration.

Wet age-related macular degeneration (wet AMD) is a primary contributor to visual impairment and severe vision loss globally, but the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells (ECs) is mainly dictated by angiogenic growth factors. Even though treatments targeting vascular endothelial growth factor (VEGF), like ranibizumab, are widely administered, more than half of patients still exhibit inadequate or null responses, suggesting the involvement of other pathogenic mechanisms. With advances in research in recent years, it has become well recognized that EC metabolic regulation plays an active rather than merely passive responsive role in angiogenesis. Disturbances of these metabolic pathways may lead to excessive neovascularization in angiogenic diseases such as wet AMD, therefore targeted modulation of EC metabolism represents a promising therapeutic strategy for wet AMD. In this review, we comprehensively discuss the potential applications of EC metabolic regulation in wet AMD treatment from multiple perspectives, including the involvement of ECs in wet AMD pathogenesis, the major endothelial metabolic pathways, and novel therapeutic approaches targeting metabolism for wet AMD.

CCR5-overexpressing mesenchymal stem cells protect against experimental autoimmune uveitis: insights from single-cell transcriptome analysis.

Autoimmune uveitis is a leading cause of severe vision loss, and animal models provide unique opportunities for studying its pathogenesis and therapeutic strategies. Here we employ scRNA-seq, RNA-seq and various molecular and cellular approaches to characterize mouse models of classical experimental autoimmune uveitis (EAU), revealing that EAU causes broad retinal neuron degeneration and marker downregulation, and that Müller glia may act as antigen-presenting cells. Moreover, EAU immune response is primarily driven by Th1 cells, and results in dramatic upregulation of CC chemokines, especially CCL5, in the EAU retina. Accordingly, overexpression of CCR5, a CCL5 receptor, in mesenchymal stem cells (MSCs) enhances their homing capacity and improves their immunomodulatory outcomes in preventing EAU, by reducing infiltrating T cells and activated microglia and suppressing Nlrp3 inflammasome activation. Taken together, our data not only provide valuable insights into the molecular characteristics of EAU but also open an avenue for innovative MSC-based therapy.

Novel therapeutic perspectives for wet age-related macular degeneration: RGD-modified liposomes loaded with 2-deoxy-D-glucose as a promising nanomedicine

Choroidal neovascularization (CNV), characterized as a prominent feature of wet age-related macular degeneration (AMD), is a primary contributor to visual impairment and severe vision loss globally, while the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells is dictated by angiogenic growth factors alone. Even though treatments targeting vascular endothelial growth factor (VEGF), like Ranibizumab, are widely administered, more than half of the patients still exhibit inadequate or null responses, emphasizing the imperative need for solutions to this problem. Here, aiming to explore therapeutic strategies from a novel perspective of endothelial cell metabolism, a biocompatible nanomedicine delivery system is constructed by loading RGD peptide-modified liposomes with 2-deoxy-D-glucose (RGD@LP-2-DG). RGD@LP-2-DG displayed good targeting performance towards endothelial cells and excellent in vitro and in vivo inhibitory effects on neovascularization were demonstrated. Moreover, our mechanistic studies revealed that 2-DG interfered with N-glycosylation, leading to the inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream signaling. Notably, the remarkable inhibitory effect on neovascularization and biocompatibility of RGD@LP-2-DG render it a highly promising and clinically translatable therapeutic candidate for the treatment of wet AMD and other angiogenic diseases, particularly in patients who are unresponsive to currently available treatments.

Burden of Disease Study of Patients with Neovascular Age-Related Macular Degeneration in Spain.

Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that causes severe and irreversible vision loss. The disease can therefore have a significant impact on the life of patients' and their families. The aim of this study was to evaluate the socio-economic burden of nAMD in Spain. The annual cost per patient with nAMD was estimated for the first, second, and third year (or beyond) of treatment since diagnosis. Several cost categories were considered including direct healthcare costs (DHC), direct non-healthcare costs (DNHC), labor productivity losses (LPL), and intangible costs (IC) related to loss of quality of life. The average annual cost per patient was estimated by assigning a unit price or financial proxy to the resources consumed per patient. Reference year of costs was 2021. The mean annual cost of nAMD was estimated at €17,265, €15,403, and €14,465 per patient in the first, second, and third year of treatment after diagnosis. There was an additional one-off cost of €744 associated with the diagnosis of nAMD. DHC accounted for most of the total annual cost per patient independent of the year of treatment since diagnosis (48% in year1; 42% in year2; 39% in year3). Similarly, DNHC had an important contribution to the total costs (32% in year1; 35% in year2; 37% in year3), followed by IC (20% in year1; 23% in year2; 24% in year3), while the contribution of patients' LPL was minimal. This study estimated a high economic burden associated with nAMD for patients and their families, the healthcare system, and society at large. There is a need to improve the management of these patients to reduce the impact of nAMD disease progression.