Management Of Retinal Diseases Research Articles

Thyroid Hormone Signaling in Retinal Development and Function: Implications for Diabetic Retinopathy and Age-Related Macular Degeneration.

Thyroid Hormones (THs) play a central role in the development, cell growth, differentiation, and metabolic homeostasis of neurosensory systems, including the retina. The coordinated activity of various components of TH signaling, such as TH receptors (THRs) and the TH processing enzymes deiodinases 2 and 3 (DIO2, DIO3), is required for proper retinal maturation and function of the adult photoreceptors, Müller glial cells, and pigmented epithelial cells. Alterations of TH homeostasis, as observed both in frank or subclinical thyroid disorders, have been associated with sight-threatening diseases leading to irreversible vision loss i.e., diabetic retinopathy (DR), and age-related macular degeneration (AMD). Although observational studies do not allow causal inference, emerging data from preclinical models suggest a possible correlation between TH signaling imbalance and the development of retina disease. In this review, we analyze the most important features of TH signaling relevant to retinal development and function and its possible implication in DR and AMD etiology. A better understanding of TH pathways in these pathological settings might help identify novel targets and therapeutic strategies for the prevention and management of retinal disease.

Geometric Correspondence-Based Multimodal Learning for Ophthalmic Image Analysis.

Color fundus photography (CFP) and Optical coherence tomography (OCT) images are two of the most widely used modalities in the clinical diagnosis and management of retinal diseases. Despite the widespread use of multimodal imaging in clinical practice, few methods for automated diagnosis of eye diseases utilize correlated and complementary information from multiple modalities effectively. This paper explores how to leverage the information from CFP and OCT images to improve the automated diagnosis of retinal diseases. We propose a novel multimodal learning method, named geometric correspondence-based multimodal learning network (GeCoM-Net), to achieve the fusion of CFP and OCT images. Specifically, inspired by clinical observations, we consider the geometric correspondence between the OCT slice and the CFP region to learn the correlated features of the two modalities for robust fusion. Furthermore, we design a new feature selection strategy to extract discriminative OCT representations by automatically selecting the important feature maps from OCT slices. Unlike the existing multimodal learning methods, GeCoM-Net is the first method that formulates the geometric relationships between the OCT slice and the corresponding region of the CFP image explicitly for CFP and OCT fusion. Experiments have been conducted on a large-scale private dataset and a publicly available dataset to evaluate the effectiveness of GeCoM-Net for diagnosing diabetic macular edema (DME), impaired visual acuity (VA) and glaucoma. The empirical results show that our method outperforms the current state-of-the-art multimodal learning methods by improving the AUROC score 0.4%, 1.9% and 2.9% for DME, VA and glaucoma detection, respectively.

Panretinal handheld OCT angiography for pediatric retinal imaging

Comprehensive visualization of retina morphology is essential in the diagnosis and management of retinal diseases in pediatric populations. Conventional imaging techniques often face challenges in effectively capturing the peripheral retina, primarily due to the limitations in current optical designs, which lack the necessary field of view to characterize the far periphery. To address this gap, our study introduces a novel ultra-widefield optical coherence tomography angiography (OCTA) system. This system, specifically tailored for pediatric applications, incorporates an ultrahigh-speed 800 kHz swept-source laser. The system’s innovative design achieves a 140° field of view while maintaining excellent optical performance. Over the last 15 months, we have conducted 379 eye examinations on 96 babies using this system. It demonstrates marked efficacy in the diagnosis of retinopathy of prematurity, providing detailed and comprehensive peripheral retinal angiography. The capabilities of the ultra-widefield handheld OCTA system in enhancing the clarity and thoroughness of retina vascularization assessments have significantly improved the precision of diagnoses and the customization of treatment strategies. Our findings underscore the system’s potential to advance pediatric ophthalmology and broaden the scope of retinal imaging.

Management of retinal diseases, therapeutic association between ophthalmology and endocrinology in the treatment of diabetic retinopathy

Introduction: Effective management of retinal diseases, especially diabetic retinopathy, is crucial for preventing severe visual complications. Collaboration between ophthalmologists and endocrinologists plays a fundamental role in the effective treatment of this condition, aiming to preserve vision and improve patients' quality of life. Methods: A bibliographic review was conducted to understand the management of retinal diseases and the therapeutic association between ophthalmology and endocrinology in the treatment of diabetic retinopathy. We used databases such as MEDLINE, PubMed, and Scielo to identify relevant articles published in the last 20 years. Inclusion and exclusion criteria were defined to ensure the selection of pertinent studies. Results: After the search and selection of articles, patterns and trends in the management of diabetic retinopathy were identified. A variety of treatment options were located, including laser photocoagulation, intravitreal injections of medications, and vitreoretinal surgery. The importance of metabolic control of diabetes to prevent retinal damage was noted. The analysis of the studies also highlighted that the interaction between these specialties ensures better clinical outcomes. Conclusion: The importance of collaboration between ophthalmologists and endocrinologists in the management of diabetic retinopathy is reinforced. An integrated approach that considers both ophthalmological and endocrinological aspects of the disease is essential to provide effective care to patients. This cooperation can result in better visual outcomes and quality of life for those affected by diabetic retinopathy.

Visual Field Tests: A Narrative Review of Different Perimetric Methods.

Visual field (VF) testing dates back to fifth century B.C. It plays a pivotal role in the diagnosis, management, and prognosis of retinal and neurological diseases. This review summarizes each of the different VF tests and perimetric methods, including the advantages and disadvantages and adherence to the desired standard diagnostic criteria. The review targets beginners and eye care professionals and includes history and evolution, qualitative and quantitative tests, and subjective and objective perimetric methods. VF testing methods have evolved in terms of technique, precision, user-friendliness, and accuracy. Consequently, some earlier perimetric techniques, often still effective, are not used or have been forgotten. Newer technologies may not always be advantageous because of higher costs, and they may not achieve the desired sensitivity and specificity. VF testing is most often used in glaucoma and neurological diseases, but new objective methods that also measure response latencies are emerging for the management of retinal diseases. Given the varied perimetric methods available, clinicians are advised to select appropriate methods to suit their needs and target disease and to decide on applying simple vs. complex tests or between using subjective and objective methods. Newer, rapid, non-contact, objective methods may provide improved patient satisfaction and allow for the testing of children and the infirm.

Diagnosis of retinal damage using Resnet rescaling and support vector machine (Resnet-RS-SVM): a case study from an Indian hospital.

This study aims to address the challenge of identifying retinal damage in medical applications through a computer-aided diagnosis (CAD) approach. Data was collected from four prominent eye hospitals in India for analysis and model development. Data was collected from Silchar Medical College and Hospital (SMCH), Aravind Eye Hospital (Tamil Nadu), LV Prasad Eye Hospital (Hyderabad), and Medanta (Gurugram). A modified version of the ResNet-101 architecture, named ResNet-RS, was utilized for retinal damage identification. In this modified architecture, the last layer's softmax function was replaced with a support vector machine (SVM). The resulting model, termed ResNet-RS-SVM, was trained and evaluated on each hospital's dataset individually and collectively. The proposed ResNet-RS-SVM model achieved high accuracies across the datasets from the different hospitals: 99.17% for Aravind, 98.53% for LV Prasad, 98.33% for Medanta, and 100% for SMCH. When considering all hospitals collectively, the model attained an accuracy of 97.19%. The findings demonstrate the effectiveness of the ResNet-RS-SVM model in accurately identifying retinal damage in diverse datasets collected from multiple eye hospitals in India. This approach presents a promising advancement in computer-aided diagnosis for improving the detection and management of retinal diseases.

The role of ultra-widefield imaging with navigated central and peripheral cross-sectional and three-dimensional swept source optical coherence tomography in ophthalmology: Clinical applications.

To assess central and peripheral retinal and choroidal diseases using ultra-widefield (UWF) fundus imaging in combination with navigated central and peripheral cross-sectional and three-dimensional (3D) swept source optical coherence tomography (SS-OCT) scans. Retrospective study involving 332 consecutive patients, with a nearly equal distribution of males and females. The mean age of patients was 52 years (range 18-92 years). Average refractive error was -3.80 D (range +7.75 to -20.75 D). The observations in this study demonstrate the efficacy of peripheral navigated SS-OCT in assessing various ocular conditions. The technology provides high-quality images of the peripheral vitreous, vitreoretinal interface, retina, and choroid, enabling visualization of vitreous floaters and opacities, retinal holes and tears, pigmented lesions, and peripheral retinal degenerations. 3D OCT scans enhance the visualization of these abnormalities and improve diagnostic and therapeutic decisions. Navigated central and peripheral cross-sectional and 3D SS-OCT scans offer significant complementary benefits in the assessment and management of retinal diseases. Their addition to UWF imaging provides a comprehensive view of central and peripheral ocular structures, aiding in early detection, precise anatomical measurements, and objective monitoring of disease progression. In addition, this technology serves as a valuable tool for patient education, a teaching tool for trainees, and documentation for medico-legal purposes.

The ever-evolving landscape of medical and surgical management of retinal disease.

The ever-evolving landscape of medical and surgical management of retinal disease.

Evidence-Based Use of Bevacizumab in the Management of Neovascular Age-Related Macular Degeneration.

Indicated for colorectal cancer for decades, bevacizumab has been widely used off label to treat retinal diseases, and the benefits of its use, specifically in neovascular age-related macular degeneration, have been demonstrated in multiple clinical trials. The intravitreal delivery of bevacizumab requires it to be aseptically repackaged into individual syringes by compounding pharmacies for use in the eye. Although the repackaging process is permitted by the US Food and Drug Administration, the resultant product does not meet the specific standards of products approved for use as ophthalmic injectables nor is the parenteral innovator solution compliant with ophthalmic standards. Studies have also demonstrated variability in the quality and quantity of repackaged bevacizumab. This narrative review summarizes the evidence and discusses the role of off-label bevacizumab in the treatment and management of retinal diseases, its mechanism of action, current challenges and provides a critical appraisal of current evidence, clinical implications, and future directions. [Ophthalmic Surg Lasers Imaging Retina 2024;55:155-162.].

Postoperative Choroidal Vascular Biomarkers in Eyes with Rhegmatogenous Retinal Detachment-Related Giant Retinal Tears

PurposeChoroidal vascularity index (CVI) and choriocapillaris flow area (CFA) are perfusion biomarkers relevant to retinal disease management. There is limited knowledge regarding these biomarkers in eyes that have been successfully treated for rhegmatogenous retinal detachment (RRD) due to giant retinal tears (GRTs). This study aimed to analyze the relationship between choroidal perfusion biomarkers and functional outcomes in surgically treated eyes with GRT-associated RRD and their fellow eyes.MethodsA total of 33 GRT eyes and 29 fellow eyes were included in this study. All RRD-GRT eyes were treated with vitrectomy and categorized into two groups based on whether additional scleral buckles (SB) were placed. Visual and choroidal features were compared between the groups.ResultsThe subjects had an average age of 55.18 years, a mean time of 2.36 weeks before surgery, and a mean follow-up time of 25.9 months. Best-corrected visual acuity (BCVA) was substantially worse in GRT eyes (1.9 logMAR) than in fellow control eyes (0.23 logMAR) but substantially improved after surgery (0.59 logMAR). There were no differences in the presurgical characteristics and BCVA between the eyes that did and did not undergo SB. Long-term CVI and CFA were lower in eyes with GRT than in their fellow eyes. Among eyes with GRT, those with SB had significantly lower CVI and CFA. Correlation analysis revealed that the CVI and CFA were positively correlated with visual outcomes (negative correlation with logMAR).ConclusionDespite successful surgical repair, long-term functional and choroidal evaluations showed permanent changes in eyes with GRT. Positive correlations between perfusion biomarkers and visual function suggest that better choroidal vasculature is associated with better visual outcomes. The results of this study highlight the benefits of analyzing choroidal vasculature biomarkers and the relationship between the choroidal anatomy and vision.

Next-Generation Nanomedicine Approaches for the Management of Retinal Diseases.

Retinal diseases are one of the leading causes of blindness globally. The mainstay treatments for these blinding diseases are laser photocoagulation, vitrectomy, and repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) or steroids. Unfortunately, these therapies are associated with ocular complications like inflammation, elevated intraocular pressure, retinal detachment, endophthalmitis, and vitreous hemorrhage. Recent advances in nanomedicine seek to curtail these limitations, overcoming ocular barriers by developing non-invasive or minimally invasive delivery modalities. These modalities include delivering therapeutics to specific cellular targets in the retina, providing sustained delivery of drugs to avoid repeated intravitreal injections, and acting as a scaffold for neural tissue regeneration. These next-generation nanomedicine approaches could potentially revolutionize the treatment landscape of retinal diseases. This review describes the availability and limitations of current treatment strategies and highlights insights into the advancement of future approaches using next-generation nanomedicines to manage retinal diseases.

The impact of artificial intelligence on retinal disease management: Vision Academy retinal expert consensus.

The aim of this review is to define the "state-of-the-art" in artificial intelligence (AI)-enabled devices that support the management of retinal conditions and to provide Vision Academy recommendations on the topic. Most of the AI models described in the literature have not been approved for disease management purposes by regulatory authorities. These new technologies are promising as they may be able to provide personalized treatments as well as a personalized risk score for various retinal diseases. However, several issues still need to be addressed, such as the lack of a common regulatory pathway and a lack of clarity regarding the applicability of AI-enabled medical devices in different populations. It is likely that current clinical practice will need to change following the application of AI-enabled medical devices. These devices are likely to have an impact on the management of retinal disease. However, a consensus needs to be reached to ensure they are safe and effective for the overall population.

Semi-supervised OCT lesion segmentation via transformation-consistent with uncertainty and self-deep supervision.

Optical coherence tomography (OCT) is a non-invasive, high-resolution ocular imaging technique with important implications for the diagnosis and management of retinal diseases. Automatic segmentation of lesions in OCT images is critical for assessing disease progression and treatment outcomes. However, existing methods for lesion segmentation require numerous pixel-wise annotations, which are difficult and time-consuming to obtain. To address this challenge, we propose a novel framework for semi-supervised OCT lesion segmentation, termed transformation-consistent with uncertainty and self-deep supervision (TCUS). To address the issue of lesion area blurring in OCT images and unreliable predictions from the teacher network for unlabeled images, an uncertainty-guided transformation-consistent strategy is proposed. Transformation-consistent is used to enhance the unsupervised regularization effect. The student network gradually learns from meaningful and reliable targets by utilizing the uncertainty information from the teacher network, to alleviate the performance degradation caused by potential errors in the teacher network's prediction results. Additionally, self-deep supervision is used to acquire multi-scale information from labeled and unlabeled OCT images, enabling accurate segmentation of lesions of various sizes and shapes. Self-deep supervision significantly improves the accuracy of lesion segmentation in terms of the Dice coefficient. Experimental results on two OCT datasets demonstrate that the proposed TCUS outperforms state-of-the-art semi-supervised segmentation methods.

Patients' Perception of Robot-Driven Technology in the Management of Retinal Diseases.

There is increasing application of robots and other artificial intelligence-driven technologies in the management of retinal disease. These technologies have the potential to meet increasing demands for retinal diseases. However, there is currently a lack of understanding of patients' attitudes towards use of robots in ophthalmology. This study investigates patients' attitudes towards robot-led management of retinal disease. Paper questionnaires were distributed to 177 patients attending intravitreal treatment (IVT) at the Princess Alexandra Eye Pavilion between 1October 2022 and 31January 2023. The questionnaire collected information on age, sex, diagnosis and postcode. In the questionnaire, patients responded to questions about their attitudes towards robot-led diagnosis, treatment decisions and IVT injections. Responses were collected using a 5-category Likert scale which was analysed using ordinal logistic regression with adjustments for age, sex and deprivation status. Those from affluent socioeconomic backgrounds were significantly (p < 0.001) more accepting of robots diagnosing and deciding on treatment, although the total number of patients who were accepting was only 26 (14.7%). Furthermore, there was an increased proportion of patients who would accept robots if the robot made fewer mistakes than doctors, if the robot reduced waiting or appointment time and if the robot was able to communicate well and have empathy; the same association with socioeconomic background remains (p < 0.001). Lastly, 116 patients (65.5%) would not be happy if IVT injections were performed by a robot; this was more likely the case if the patient was female (p = 0.04) or from a more deprived socioeconomic background (p < 0.001). Attitudes towards robot involvement in diagnosis and management of retinal disease are significantly associated with socioeconomic backgrounds and sex. Additional studies are required to further investigate these determinants of robot receptiveness to ensure acceptance and compliance with treatment with these new technologies.

Impact of an immersive, interactive medical education initiative on guideline-based retinal disease management knowledge/competence and effectual practice change

BackgroundRetinal diseases, including wet or dry age-related macular degeneration, diabetic macular edema, and diabetic retinopathy (DR), are underdiagnosed and undertreated in the United States. Clinical trials support the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) therapies for several retinal conditions, but real-world data suggest underuse by clinicians, resulting in patients experiencing poorer visual outcomes over time. Continuing education (CE) has demonstrated effectiveness at changing practice behaviors, but more research is needed to understand whether CE can help address diagnostic and treatment gaps.MethodsThis test and control matched pair analysis examined pre-/post-test knowledge of retinal diseases and guideline-based screening and intervention among 10,786 healthcare practitioners (i.e., retina specialists, ophthalmologists, optometrists, primary care providers, diabetes educators, pharmacists/managed care specialists, and other healthcare providers, such as registered nurses, nurse practitioners, and physician assistants) who participated in a modular, interactive CE initiative. An additional medical claims analysis provided data on practice change, evaluating use of VEGF-A inhibitors among retina specialist and ophthalmologist learners (n = 7,827) pre-/post-education, compared to a matched control group of non-learners. Outcomes were pre-/post-test change in knowledge/competence and clinical change in application of anti-VEGF therapy, as identified by the medical claims analysis.ResultsLearners significantly improved knowledge/competence scores on early identification and treatment, identifying patients who could benefit from anti-VEGF agents, using guideline-recommended care, recognizing the importance of screening and referral, and recognizing the importance of early detection and care for DR (all P-values = 0.003 to 0.004). Compared with matched controls, learners’ incremental total injections for anti-VEGF agents for retinal conditions increased more after the CE intervention (P < 0.001); specifically, there were 18,513 more (new) anti-VEGF injections prescribed versus non-learners (P < 0.001).ConclusionsThis modular, interactive, immersive CE initiative resulted in significant knowledge/competence gains among retinal disease care providers and changes in practice-related treatment behaviors (i.e., appropriate consideration and greater incorporation of guideline-recommended anti-VEGF therapies) among participating ophthalmologists and retina specialists compared to matched controls. Future studies will utilize medical claims data to show longitudinal impact of this CE initiative on treatment behavior among specialists and impact on diagnosis and referral rates among optometrists and primary care providers who participate in future programming.

OculusGraphy: Signal Analysis of the Electroretinogram in a Rabbit Model of Endophthalmitis Using Discrete and Continuous Wavelet Transforms.

The electroretinogram is a clinical test used to assess the function of the photoreceptors and retinal circuits of various cells in the eye, with the recorded waveform being the result of the summated response of neural generators across the retina. The present investigation involved an analysis of the electroretinogram waveform in both the time and time-frequency domains through the utilization of the discrete wavelet transform and continuous wavelet transform techniques. The primary aim of this study was to monitor and evaluate the effects of treatment in a New Zealand rabbit model of endophthalmitis via electroretinogram waveform analysis and to compare these with normal human electroretinograms. The wavelet scalograms were analyzed using various mother wavelets, including the Daubechies, Ricker, Wavelet Biorthogonal 3.1 (bior3.1), Morlet, Haar, and Gaussian wavelets. Distinctive variances were identified in the wavelet scalograms between rabbit and human electroretinograms. The wavelet scalograms in the rabbit model of endophthalmitis showed recovery with treatment in parallel with the time-domain features. The study compared adult, child, and rabbit electroretinogram responses using DWT and CWT, finding that adult signals had higher power than child signals, and that rabbit signals showed differences in the a-wave and b-wave depending on the type of response tested, while the Haar wavelet was found to be superior in visualizing frequency components in electrophysiological signals for following the treatment of endophthalmitis and may give additional outcome measures for the management of retinal disease.

Use of physician extenders in ophthalmology: pros.

The goal of this review is to provide a description of the potential role of physician extenders within ophthalmology with a specific focus on the retina field. In this editorial, the evolving role of physician extenders (e.g. physician assistants, nurse practitioners) in medicine and ophthalmology is discussed. Within ophthalmology, an experiential discussion is provided regarding the opportunities to utilize physician extenders to expand the bandwidth of subspecialists and increase access for patient care. Physician extenders, such as physician assistants, provide a unique opportunity for ophthalmology to innovate next-generation care delivery models. The roles for physician extenders throughout highly specialized fields in medicine have become a critical component for team-based patient care. Within retina and other ophthalmic subspecialties, physician extenders can enable top-of-license practice for physicians, while directly expanding the umbrella of care the specialist can provide through the physician extender's role in chronic disease medical management. The deployment of a physician assistants within the retina care team provided greater access for patients requiring ongoing medical monitoring and triage for acute issues, while expanding the retina specialist's ability to see a higher volume of higher acuity patients and those patients requiring procedural/surgical interventions. Importantly, the physician assistant's role is focused exclusively on medical management of retinal diseases with all procedures being performed by the retina specialist.

Intravitreal Injection Planning during COVID-19 Pandemic: A Retrospective Study of Two Tertiary University Centers in Italy.

The COVID-19 pandemic has hampered the optimum management of retinal diseases. This study examined the impact of the pandemic on the intravitreal-injection practice in two academic centers in Italy along with the related medico-legal implications. A retrospective analysis of electronic medical records from 16 March 2020 to 14 March 2021 at the ophthalmological departments of University of Cagliari (SGD) and University Magna Græcia of Catanzaro (UMG) was conducted. The data collected between 16 March 2020 and 14 June 2020 (lockdown), 15 June 2020 and 13 September 2020 (unlock), and 14 September 2020 and 14 March 2021 (second wave) were compared with those of the same period of the previous year. Weekly data on the administered drug and the number and type of treated disease were collected and analyzed. During the lockdown, a drop of 59% at SGD (p < 0.00001) and 77% at UMG (p < 0.00001) in intravitreal injections was found. In the first year of the pandemic, the reduction in injections was approximately of 27% (p < 0.0008) and 38% (p < 0.0001) at SGD and UMG, respectively. The COVID-19-related containment measures and the health resources redistribution have led to a delay in the treatment of chronic diseases of the retina, prioritizing the undeferrable ones. The lack of management guidelines has conceived relevant ethical and medico-legal issues that need to be considered in future measures planning.

Long-term efficacy and safety of RazumabTM (biosimilar ranibizumab) in Indian patients with retinal diseases: results from retrospective REAR RD-2 study

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; To evaluate risk factors associated with retinal diseases and efficacy and safety of Razumab&lt;sup&gt;TM&lt;/sup&gt; (biosimilar ranibizumab) in the management of retinal diseases in Indian patients with wet age-related macular degeneration (wet AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and myopic choroidal neovascularization (mCNV).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; In the retrospective, observational REAR RD-2 study, all patients with retinal diseases who were treated with biosimilar ranibizumab were included from multiple Indian sites. The demographic parameters, disease characteristics and treatment details were recorded. Efficacy assessments included improvement in best corrected visual acuity (BCVA), and decrease in central subfield thickness (CSFT), intra-retinal fluid (IRF) and sub-retinal fluid (SRF) from baseline to week 48.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; Data of 1422 patients (wet AMD-27.57%; DME-30.7%, RVO-33.47%; mCNV-5.48%), who were treated with biosimilar ranibizumab, was analyzed. The most common age group of patients was 61-70 years (36.6%). The most common ocular risk factor identified was glaucoma (24.90%). A total of 85.72% patients were treatment naïve and 14.28% were previously treated patients. Biosimilar ranibizumab treatment resulted in significant (p&amp;lt;0.05) improvements in the mean BCVA and CSFT, and the proportion of patients with IRF and SRF was significantly reduced throughout the treatment. No new safety concerns with biosimilar ranibizumab were observed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Retinal diseases are more common in the age group of 61-70 years. Glaucoma was the most common ocular risk factor identified for retinal diseases. Long-term treatment with biosimilar ranibizumab was effective and well-tolerated in retinal diseases including wAMD, DME, RVO and mCNV in real-world Indian scenario. &lt;/p&gt;&lt;p&gt;&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;

Melatonin loaded hybrid nanomedicine: DoE approach, optimization and in vitro study on diabetic retinopathy model

Melatonin (MEL) is a pleiotropic neurohormone of increasing interest as a neuroprotective agent in ocular diseases. Improving the mucoadhesiveness is a proposed strategy to increase the bioavailability of topical formulations. Herein, the design and optimization of MEL-loaded lipid-polymer hybrid nanoparticles (mel-LPHNs) using Design of Experiment (DoE) was performed. LPHNs consisted of PLGA-PEG polymer nanoparticles coated with a cationic lipid-shell. The optimized nanomedicine showed suitable size for ophthalmic administration (189.4 nm; PDI 0.260) with a positive surface charge (+39.8 mV), high encapsulation efficiency (79.8 %), suitable pH and osmolarity values, good mucoadhesive properties and a controlled release profile. Differential Scanning Calorimetry and Fourier-Transform Infrared Spectroscopy confirmed the encapsulation of melatonin in the systems and the interaction between lipids and polymer matrix. Biological evaluation in an in vitro model of diabetic retinopathy demonstrated enhanced neuroprotective and antioxidant activities of mel-LPHNs, compared to melatonin aqueous solution at the same concentration (0.1 and 1 μM). A modified Draize test was performed to assess the ocular tolerability of the formulation showing no signs of irritation. To the best our knowledge, this study reported for the first time the development of mel-LPHNs, a novel and safe hybrid platform suitable for the topical management of retinal diseases.