Objectives: Insulin plays a crucial role in neuronal survival and oxidative stress modulation, making it a potential therapeutic target. This study investigates the effects of insulin in combination with a mesenchymal cell-derived secretome in patients with degenerative neuroretinal diseases. Methods: Sixty-four patients with severe neuroretinal diseases who had previously undergone the Limoli Retinal Restoration Technique (LRRT) were included in this longitudinal study and divided into groups: group 1 received a single injection of 5 units of insulin lispro into the suprachoroidal space of the worse-seeing eye; group 2 received insulin injection in the better-seeing eye. Retinal function was assessed using microperimetry (MY) before and after treatment (approximately 1 year for eye drops). Group 3 consisted of patients who demonstrated improvement in MY after insulin injection. These patients continued treatment with daily insulin eye drops. Results: In group 1, insulin-treated eyes showed a significant increase in retinal sensitivity from 10.09 dB to 10.75 dB (p = 0.0067), while untreated eyes declined from 12.35 dB to 11.92 dB (p = 0.0448). In group 2, insulin-treated eyes improved from 10.8 dB to 11.63 dB (p = 0.05), whereas untreated eyes exhibited a decline from 8.68 dB to 8.50 dB (p = 0.6771). In group 3, patients using insulin eye drops showed a stabilization or mild increase in retinal sensitivity, from 11.39 dB to 11.73 dB (p = 0.231). Conclusions: The addition of insulin in patients previously treated with the LRRT was associated with improved sensitivity and a stabilizing effect on neuroretinal function.

Retinal ischemic perivascular lesions (RIPLs) are characteristic focal thinning of the inner nuclear layer, with an upward expansion of the outer nuclear layer identified by spectral domain optical coherence tomography (SD-OCT), causing a focal irregular appearance of the middle retina. RIPLs result from retinal hypoperfusion in the deep capillary plexus, as a legacy of paracentral acute middle maculopathy, representing permanent anatomical markers of prior ischemic events. Although frequently found incidentally during routine eye examinations, RIPLs may provide insights into subclinical vascular damage that underpins various cardio- and cerebrovascular diseases. The aim of this narrative review is to summarize the relationships of RIPLs with retinal and systemic vascular diseases, including arterial hypertension, coronary artery disease, carotid artery stenosis, atrial fibrillation, stroke, sickle cell disease, and diabetes mellitus. Cardiovascular and metabolic diseases, which are the leading causes of morbidity and mortality worldwide, often remain asymptomatic for years despite early structural changes until severe adverse events occur. Noninvasive retinal biomarkers such as RIPLs, which are readily and noninvasively detected through SD-OCT scans, could help in the early detection and stratification of patients at risk for cardiovascular diseases, facilitate timely medical interventions and lifestyle changes, and ultimately improve disease prevention in a "personalized medicine" approach. While further research is needed to establish the prevalence of RIPLs in the general population and their full clinical significance, advances in ophthalmic imaging technologies combined with rapid progress in artificial intelligence applications in medical research could accelerate the development of RIPLs in retinal imaging-based oculomics.

Vision impairment and blindness are a major global health challenge where gaps in the ophthalmology workforce limit access to specialist care. We evaluate AMIE, a medically fine-tuned conversational system based on Gemini with integrated web search and self-critique reasoning, using real-world clinical vignettes that reflect scenarios a general ophthalmologist would be expected to manage. We conducted two complementary evaluations: (1) a human-AI interactive diagnostic reasoning study in which ophthalmologists recorded initial differentials and plans, then reviewed AMIE's structured output and revised their answers; and (2) a masked preference and quality study comparing AMIE's narrative outputs with case author reference answers using a predefined rubric. AMIE showed standalone diagnostic performance comparable to clinicians at baseline. Crucially, after reviewing AMIE's responses, ophthalmologists tended to rank the correct diagnosis higher, reached greater agreement with one another, and enriched their investigation and management plans. Improvements were observed even when AMIE's top choice differed from or underperformed the clinician baseline, consistent with a complementary effect in which structured reasoning support helps clinicians re-rank rather than simply accept the model output. Preferences varied by clinical grade, suggesting opportunities to personalise responses by experience. Without ophthalmology-specific fine-tuning, AMIE matched clinician baseline and augmented clinical reasoning at the point of need, motivating multi-axis evaluation, domain adaptation, and prospective multimodal studies in real-world settings.

This research wanted to explore the recent and future therapeutic possibilities in patients affected by neuroretinal degeneration through the use of stem cells. There are numerous degenerative neuroretinal diseases, each with its own etiology and genetics, including glaucoma, age-related macular degeneration, degenerative myopia, diabetic retinopathy, inherited retinal dystrophies, etc. Molecular dysfunction may initially affect neural cells, ganglion cells, photoreceptors (cones or rods), and support cells, such as Müller cells or retinal pigment epithelium cells. As the disease progresses, dysfunction and subsequent loss of these cells lead to severe sensory impairment: the end result is the permanent and irreversible loss of vision or part of it. In the last two decades, new therapeutic avenues aimed at treating degenerative eye diseases have been hypothesized. These approaches include restoration of defective genes, when the disease is caused by a genetic defect, and stem cell transplantation to replace dead cells or repair defective ones, regardless of the cause. Moreover, for gene therapy to be effective, it should be applied before the retina is compromised by the degenerative disease. For this reason, the interest of the scientific community has also turned to restorative strategies based on the use of stem cells, either systemically injected or locally implanted. There are numerous advantages to using cell therapy in ophthalmology. The surgical approach is theoretically simple and potentially within the reach of ophthalmologists. The effect of cell transplantation can be easily monitored with currently available imaging methods. According to the case, the contralateral eye could be used as a control. Long-term immunosuppressive treatment is not required either in the case of heterologous implants because of the immune privilege of the eye or of autologous cells. In summary, the study investigated the various issues described above in light of the new regenerative therapies with stem cells.

PURPOSE OF REVIEW:Given the increasing global burden of diabetic retinopathy and the rapid advancements in artificial intelligence, this review aims to summarize the current state of artificial intelligence technology in diabetic retinopathy detection and management, assessing its potential to improve care and visual outcomes in real-world settings. RECENT FINDINGS:Most recent studies focused on the integration of artificial intelligence in the field of diabetic retinopathy screening, focusing on real-world efficacy and clinical implementation of such artificial intelligence models. Additionally, artificial intelligence holds the potential to predict diabetic retinopathy progression, enhance personalized treatment strategies, and identify systemic disease biomarkers from ocular images through 'oculomics', moving towards a more precise, efficient, and accessible care. The emergence of foundation model architectures and generative artificial intelligence, which more clearly reflect the clinical care process, may enable rapid advances in diabetic retinopathy care, research and medical education. SUMMARY:This review explores the emerging technology of artificial intelligence to assess the potential to improve patient outcomes and optimize personalized management in healthcare delivery and medical research. While artificial intelligence is expected to play an increasingly important role in diabetic retinopathy care, ongoing research and clinical trials are essential to address implementation issues and focus on long-term patient outcomes for successful real-world adoption of artificial intelligence in diabetic retinopathy.

center dot PURPOSE: To evaluate the risk of acute cardiovascular events (CVE), including cardiovascular diseases, cerebrovascular diseases, and all-cause mortality in patients with paracentral acute middle maculopathy (PAMM). center dot DESIGN: Retrospective cohort study. center dot METHODS: We studied 43 individuals with optical coherence tomography-documented PAMM attending Moorfields Eye Hospital between January 2014 and June 2021. We excluded patients with preceding ( < 2 years) major adverse cardiac events. We stratified patients by age ( < 50 and >= 50 years) and whether associated with retinal vascular diseases (RVD) or isolated (iPAMM). We assessed risk factors, clinical characteristics, and visual prognosis of the patients. CVE risk was estimated using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards regression. center dot RESULTS: In young patients with iPAMM patients ( n = 12), underlying predisposing factors included six (50%) sickle cell disease and five (41.6%) others, including breakthrough bleeding in pregnancy, migraine, genetic cardiomyopathy, amphetamine use; among those with PAMM + RVD ( n = 12) one (9%) had a vascular disorder, and four (44.4%) oral contraceptive use. In the older group of 20 patients, 15 (75%) had at least one coronary risk factor. During a median follow-up of 14 months (range 12-54), older subjects with iPAMM had a higher risk of developing CVE than those with PAMM + RVD ( P < .001). Notably, iPAMM displayed a significantly earlier peak in peri-PAMM CVE risk compared to PAMM + RVD (median: one month, range 1-40 months vs 36 months, range 12-54 months). Relative to those with PAMM + RVD, risk of CVE was significantly higher in patients with iPAMM, adjusted for age and sex (hazard ratio: 6.37, 95% confidence interval 1.68-24.14, P = .017). No young patients experienced adverse CVE. At baseline, older iPAMM patients mean best corrected visual acuity of 0.7 (0-1.8) logarithm of the minimum angle resolution, which improved significantly to 0.2 (01.30) logarithm of the minimum angle resolution at the latest visit ( P = .033). center dot CONCLUSIONS: Young individuals with iPAMM have a higher prevalence of predisposing factors compared to those presenting with combined PAMM + RVD. Older patients with iPAMM had a higher risk of CVE than those with PAMM + RVD, especially in the peri-onset timeframe. This suggests the need for a prompt cardiovascular assessment to rule out systemic etiologies and optimize cardiovascular risk factors, in addition to ongoing ophthalmology input. (Am J Ophthalmol 2024;267: 286-292. (c) 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ))

Age-related macular degeneration (AMD) and age-related neurological diseases (ANDs), such as Alzheimer’s and Parkinson’s Diseases, are increasingly prevalent conditions that significantly contribute to global morbidity, disability, and mortality. The retina, as an accessible part of the central nervous system (CNS), provides a unique window to study brain aging and neurodegeneration. By examining the associations between AMD and ANDs, this review aims to highlight novel insights into fundamental mechanisms of aging and their role in neurodegenerative disease progression. This review integrates knowledge from the emerging field of aging research, which identifies common denominators of biological aging, specifically loss of proteostasis, impaired macroautophagy, mitochondrial dysfunction, and inflammation. Finally, we emphasize the clinical relevance of these pathways and the potential for cross-disease therapies that target common aging hallmarks. Identifying these shared pathways could open avenues to develop therapeutic strategies targeting mechanisms common to multiple degenerative diseases, potentially attenuating disease progression and promoting the healthspan.

Cataracts can reduce the quality of vision in visually impaired patients who already have a visual impairment. The most common causes of low vision include age-related macular degeneration (AMD), high myopia (HM), diabetic retinopathy (DR), glaucoma (GL), and inherited degenerative ocular diseases. The surgery aims to improve their independence, quality of life, and ability to engage in daily, social, and work activities. Phacoemulsification and intraocular lens (IOL) implantation, combined with visual rehabilitation, can improve visual acuity of visually impaired patients. Therefore, comprehensive guidelines for cataract surgery in patients with low vision would be beneficial to ensure optimal surgical outcomes by improving surgical planning, execution, and postoperative care, along with a well-coordinated rehabilitation process. In cases of reduced metabolism, such as low vision, oxidative stress can be aggravated by light exposure and surgical interventions. Thus, maintaining redox balance is crucial for stabilizing retinal conditions. Patients with visual impairments rely on retinal regions with the greatest residual function, and cataract surgery aims to enhance focus on these areas, improving reading quality and reducing scotoma perception. Thorough informed consent is crucial, ensuring that patients are fully aware of the potential risks, benefits, and limitations of surgery. Close postoperative follow-up in the first 6 months is crucial to detect and manage any complications promptly, such as reactivation of maculopathy. The aim of this work is to establish potential guidelines for optimal rehabilitation outcomes through careful literature analysis.

PURPOSE:To investigate the frequency and type of artifacts on OCT angiography (OCTA) images and the relationship with clinical features in eyes with diabetic macular edema (DME). DESIGN:Retrospective, cross-sectional comparative study. SUBJECTS:One hundred ninety-two eyes of 140 patients with DME were included. METHODS:Medical records, OCT and OCTA images (Spectralis), and ultrawidefield color fundus photographs (Optos plc) were evaluated. MAIN OUTCOME MEASURES:The frequency of artifact types (segmentation, motion, projection artifact, and low signal) was determined. The relationships between artifact types and clinical features such as best-corrected visual acuity (BCVA), mean central retinal thickness (CRT), foveal avascular zone (FAZ) area, perimeter, circularity index, perfusion density (PD), vessel density (VD), fractal dimension (FD) in the superficial capillary plexus, intermediate capillary plexus (ICP), and deep capillary plexus (DCP), flow voids (FVs) in the choriocapillaris, presence of hard exudate (HE), and cataract were determined. RESULTS:The mean age was 71.6 ± 11.4 years, and 86 (61.4%) out of 140 were men. Artifacts were present in 63 (32.8%) of 192 eyes. Twenty-nine (15.1%) eyes had segmentation artifacts, 12 (6.3%) had motion artifacts, 11 (5.7%) had projection artifacts, and 18 (9.4%) had low signal. Best-corrected visual acuity, PD, VD, and FD in ICP and DCP were significantly lower; and CRT, FAZ area and perimeter in ICP and DCP, and presence of cystoid macular edema, HE, and cataract were higher in eyes with artifacts versus eyes without artifacts (P < 0.05 for each). Multivariate linear regression analysis showed a significant association between segmentation artifacts and decreased BCVA (odds ratio [OR], 5.277; P = 0.02), increased CRT (OR, 1.015; P < 0.001), increased area of FAZ in DCP (OR, 6.625; P = 0.02), and increased perimeter of FAZ in DCP (OR, 1.775; P < 0.04); there was also a significant association between projection artifacts and presence of HE (OR, 2.017; P = 0.02) and between motion artifacts and presence of cataract (OR, 4.102; P = 0.01). CONCLUSIONS:OCT angiography artifacts were present in one third of DME eyes, with segmentation artifacts being the most frequent type. Determining OCTA artifacts is crucial to ensure accurate clinical evaluation. These data could help in developing more standardized clinical protocols for image acquisition and interpretation used in clinical practice and research. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Introduction: This study aimed to evaluate the association between macular optical coherence tomography angiography (OCT-A) metrics, characteristics of ultrawide field (UWF) imaging, and cerebrovascular disease in patients with diabetes mellitus (DM) with different stages of diabetic retinopathy (DR). Methods: 516 eyes of 258 DM patients were enrolled in two centers (Milan and Belfast). UWF color fundus photos (CFPs) were obtained with Optos California (Optos, PLC) and graded for both DR severity and predominantly peripheral lesions presence (>50% of CFP lesions) by two independent graders. OCT-A (3 × 3 mm), available in 252 eyes of 136 patients, was used to determine perimeter, area, and circularity index of the foveal avascular zone and vessel density (VD); perfusion density (PD); fractal dimension on superficial, intermediate (ICP), and deep capillary plexuses; flow voids (FVs) in the choriocapillaris. Results: Out of 516 eyes, 108 eyes (20.9%) had no DR, and 6 eyes were not gradable. The remaining 402 eyes were as follows: 10.3% (53) had mild nonproliferative DR (NPDR), 38.2% (197) had moderate NPDR, 11.8% (61) had severe NPDR, and 17.6% (91) had proliferative DR. A worse DR stage was associated with a history of stroke (p = 0.044). Logistic regression analysis after taking into account sex, type of DM, age, DM duration, and OCT-A variables found that PD and VD on ICP were significantly associated with presence of stroke and DR severity. Conclusion: OCT-A metrics show an association with the presence of cerebrovascular complications, providing potentially useful parameters to estimate vascular risk in patients with DM.

PURPOSE:To investigate the sociodemographic profile, the association with retinal vascular diseases (RVD) and systemic comorbidities, and visual outcomes of patients with paracentral acute middle maculopathy (PAMM) in a large, ethnically diverse single-center cohort. DESIGN:Retrospective cohort study. METHODS:Electronic health record query for all patients presenting with PAMM at Moorfields Eye Hospital, London, was completed. Detailed demographic, clinical, and systemic information were collected and analyzed. RESULTS:A total of 78 eyes of 78 patients with confirmed PAMM were included in the study. Forty patients (51.3%) presented with no RVD, 20 patients (25.6%) with retinal vein occlusion (RVO), 16 patients (20.5%) with retinal artery occlusion (RAO), and 2 patients (2.6%) with concomitant RAO and RVO. Patients with PAMM+RAO were older than those with RVO (P = .02) and more likely to have a history of major adverse cardiovascular events (MACE) (P = .01), with a significantly worse presenting best corrected visual acuity (BCVA) (20/50) compared to patients with RVO (P = .02) and no RVD (P < .001). Individuals with isolated PAMM had a significantly higher prevalence of previous MACE (P = .04) and sickle cell disease (SCD) (P = .04) compared to those with RVO. At the last follow-up, 64 patients (85.3%) had a good BCVA (>20/32). CONCLUSIONS:The significant association of PAMM with RVD supports the hypothesis of an ischemic etiology. Individuals with isolated PAMM had a higher prevalence of MACE and SCD. Thus, it is important to prompt immediate referral for a comprehensive systemic evaluation. Across the whole cohort, PAMM was associated with good BCVA improvement during follow-up, indicating a good visual prognosis.

The retina and the optic nerve are considered extensions of the central nervous system (CNS) and thus can serve as the window for evaluation of CNS disorders. Spectral domain optical coherence tomography (OCT) allows for detailed evaluation of the retina and the optic nerve. OCT can non-invasively document changes in single retina layer thickness and structure due to neuronal and retinal glial cells (RGC) modifications in systemic and local inflammatory and neurodegenerative diseases. These can include evaluation of retinal nerve fibre layer and ganglion cell complex, hyper-reflective retinal spots (HRS, sign of activated microglial cells in the retina), subfoveal neuroretinal detachment, disorganization of the inner retinal layers (DRIL), thickness and integrity of the outer retinal layers and choroidal thickness. This review paper will report the most recent data on the use of OCT as a non invasive imaging biomarker for evaluation of the most common systemic neuroinflammatory and neurodegenerative/neurocognitive disorders in the adults and in paediatric population. In the adult population the main focus will be on diabetes mellitus, multiple sclerosis, optic neuromyelitis, neuromyelitis optica spectrum disorders, longitudinal extensive transverse myelitis, Alzheimer and Parkinson diseases, Amyotrophic lateral sclerosis, Huntington’s disease and schizophrenia. In the paediatric population, demyelinating diseases, lysosomal storage diseases, Nieman Pick type C disease, hypoxic ischaemic encephalopathy, human immunodeficiency virus, leukodystrophies spinocerebellar ataxia will be addressed.

AIM:The purpose of this review is to examine the applications of novel digital technology domains for the screening and management of patients with diabetic retinopathy (DR).METHODS:A PubMed engine search was performed, using the terms "Telemedicine", "Digital health", "Telehealth", "Telescreening", "Artificial intelligence", "Deep learning", "Smartphone", "Triage", "Screening", "Home-based", "Monitoring", "Ophthalmology", "Diabetes", "Diabetic Retinopathy", "Retinal imaging". Full-text English language studies from January 1, 2010, to February 1, 2022, and reference lists were considered for the conceptual framework of this review.RESULTS:Diabetes mellitus and its eye complications, including DR, are particularly well suited to digital technologies, providing an ideal model for telehealth initiatives and real-world applications. The current development in the adoption of telemedicine, artificial intelligence and remote monitoring as an alternative to or in addition to traditional forms of care will be discussed.CONCLUSIONS:Advances in digital health have created an ecosystem ripe for telemedicine in the field of DR to thrive. Stakeholders and policymakers should adopt a participatory approach to ensure sustained implementation of these technologies after the COVID-19 pandemic. This article belongs to the Topical Collection "Diabetic Eye Disease", managed by Giuseppe Querques.