Purpose:To compare 1-year best-corrected visual acuity (BCVA) after pars plana vitrectomy (PPV) for lamellar macular hole (LMH) between combined phacovitrectomy and sequential strategies, and to explore factors associated with postoperative visual outcome. Methods:Multicenter observational study of adults with optical coherence tomography (OCT)-confirmed LMH undergoing PPV. Surgical sequence was classified as combined surgery or sequential surgery (PPV→phacoemulsification, PPV in pseudophakic eyes, or PPV without subsequent cataract extraction). LMHs were classified as tractional, mixed, or degenerative based on OCT criteria. BCVA (logMAR) was recorded preoperatively and at 1 year. Ceiling effect was defined as achieving 1-year BCVA ≤0.22 logMAR. Independent predictors of 1-year BCVA were assessed using a linear mixed-effects model with a random intercept for patient. Results:A total of 175 eyes from 167 patients were included; 1-year BCVA was available for 126 eyes (72.0%), whereas 49 eyes (28.0%) had missing 1-year BCVA. Among eyes with recorded 1-year BCVA, no statistically significant differences were detected between combined and sequential surgery (0.2 [0.1-0.3] vs 0.2 [0.1-0.3]; p = 0.939) or among LMH subtypes. Overall, BCVA improved from 0.4 (IQR 0.3-0.5) to 0.2 (0.1-0.3) at 1 year. In ceiling-effect analysis, baseline BCVA (p = 0.013) and the presence of isolated epiretinal membrane (p = 0.032) were associated with achieving BCVA ≤0.22 logMAR. In the mixed-effects model, baseline BCVA was the only independent predictor of 1-year BCVA (β = 0.60; 95% CI 0.32-0.89; p < 0.001). Conclusion:PPV for LMH was associated with visual improvement at 1 year, and the study did not detect statistically significant differences in final BCVA between combined and sequential strategies or among LMH subtypes. Baseline BCVA was the main determinant of 1-year outcomes, supporting individualized selection of surgical sequence based on lens status and shared patient-surgeon preferences.

Background: Age-related macular degeneration (AMD) is a multifactorial retinal disease in which alterations in lipid metabolism and dysregulation of the complement system play a central role. The aim of this study was to characterize a novel double-knockout (DK) mouse model deficient in apolipoprotein E and complement factor H (ApoE-/-Cfh-/-) as an experimental model of early and intermediate AMD. Methods: ApoE-/-Cfh-/- mice and wild-type controls underwent comprehensive morphological, ultrastructural, biochemical, and molecular analyses. Retinal and retinal pigment epithelium (RPE) integrity, Bruch's membrane (BM) morphology, lipid accumulation, complement activation, angiogenic signaling, and synaptic organization were evaluated using histology, electron microscopy, immunohistochemistry, biochemical assays, and gene expression analyses. Results: DK mice exhibited significant RPE thinning, disruption of tight junctions, vacuolization, and BM thickening (p < 0.05). Lipid accumulation and plasma lipid levels significantly increased compared with controls (p < 0.01). Complement activation was significantly enhanced, as evidenced by increased C5b-9 deposition (p < 0.01). In addition, DK mice exhibited increased vascular endothelial growth factor expression (p < 0.05), altered matrix metalloproteinase activity (p < 0.05), and significant synaptic disorganization between photoreceptors and second-order neurons (p < 0.05). Conclusions: The ApoE-/-Cfh-/- mouse reproduces key molecular and structural features of early and intermediate retinal degeneration with statistically significant alterations. Although it does not progress to advanced disease stages, it represents a valuable model to investigate several factors of AMD pathogenesis and evaluate therapeutic strategies targeting early disease mechanisms.

Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) are leading causes of visual impairment and require long-term intravitreal anti-vascular endothelial growth factor (VEGF) therapy. However, treatment burden and suboptimal real-world outcomes remain major challenges. Faricimab is a bispecific monoclonal antibody that simultaneously inhibits VEGF-A and angiopoietin-2 (Ang-2), a key mediator of vascular destabilization, leakage and inflammation, offering a novel dual-pathway approach aimed at improving efficacy and durability. This narrative review summarizes evidence from pivotal clinical trials and recent real-world studies evaluating the efficacy, durability, and safety of faricimab in patients with nAMD and DME. Real-world evidence from international cohorts and emerging data from Spanish routine clinical practice largely corroborate previous findings, showing anatomical improvements, stable or improved visual outcomes, and reduced treatment burden in treatment-naïve and previously treated eyes. Overall, the evidence reviewed indicates that faricimab is an effective and well-tolerated therapeutic option that may help address unmet needs in the long-term management of nAMD and DME. Importantly, data from real-world clinical practice are consistent with findings from pivotal trials, supporting the translation of faricimab’s outcomes into routine care.

Introduction:The increasing global prevalence of childhood myopia has become a significant public health concern. Among environmental risk factors, reduced outdoor activity (OA) has been consistently associated with a higher incidence of myopia. While questionnaires are traditionally used to estimate sunlight exposure, conjunctival ultraviolet autofluorescence (CUVAF) has emerged as an objective biomarker for cumulative ocular UV exposure. Methods:A cross-sectional case-control study was conducted among 2,616 children aged 7-8 and 11-12 years from 39 schools in Madrid, Spain. After reviewing the exclusion criteria, 354 children were removed from the study, leaving 2,262 participants in the sample. Participants were classified based on refractive error and underwent ocular examination and lifestyle questionnaires. The CUVAF area was measured in 1,129 children for logistical reasons, and they were grouped according to weekly time spent in OA (<7 vs. ≥7 h). Multivariate logistic regression and ROC curve analyses were performed to assess associations between OA, CUVAF, and myopia. Results:Myopia prevalence was significantly lower in children spending ≥7 h per week in OA than those with less exposure (9% vs. 18%; p < 0.001). CUVAF presence was strongly associated with higher OA and lower prevalence of myopia. A negative correlation was observed between CUVAF and myopia across schools (r = -0.6; p < 0.05). A diagnostic model using age-adjusted CUVAF showed a 91.9% probability of being non-myopic (negative predictive value) (positive predictive value: 10.79%; sensitivity: 76.5%; specificity: 29.6%). Each additional hour of OA reduced myopia risk by 2% (OR = 0.98; p = 0.01), while ≥7 h weekly halved the risk (OR = 0.50; p < 0.001). Conversely, the prevalence of high CUVAF increased with greater OA (OR = 2.54 for ≥7 h/week). Conclusion:CUVAF is a reliable, objective, and non-invasive biomarker of outdoor light exposure that correlates inversely with myopia in children. The larger sample size of this study supports the potential clinical utility of CUVAF not only for evaluating an individual's risk of myopia development during childhood but also for monitoring adherence to lifestyle modifications aimed at its prevention. Its integration into routine screening could improve early detection and personalized prevention strategies for childhood myopia.

OBJECTIVE:To evaluate the visual outcomes in neovascular age-related macular degeneration (nAMD) eyes initiating anti-vascular endothelial growth factor treatment with baseline visual acuity (VA) ≥70 letters. METHODS:Multicentre, real-world, and national database study. Demographics, VA, number of injections, and patient visit data were collected using a validated online tool. Subgroup analysis included 2 nonoverlapping participant groups defined by baseline VA: Good vision eyes (GVE, "70-100 letters") and non-GVE ("0-69 letters") at 12, 24, and 36 months. RESULTS:A total of 3 138 eyes (2 520 patients) were included in the analysis, followed up for 12 (n = 2 426; 77.3%), 24 (n = 1 793; 57.1%), and 36 months (n = 1 167; 37.2%). GVE had significantly better 24-month final VA (71.0 ± 13.8 vs 52.3 ± 23.2; p < 0.001) than NGVE. Mean VA change (letters) at 12, 24, and 36 months of follow-up was significantly lower in the GVE -2.4 (-3.1, -1.6), -4.5 (-5.6, -3.5), and -7.8 (-9.4, -6.2) than in NGVE +6.7 (5.8, 7.6), +5.0 (3.8, 6.2), and +4.0 (2.5, 5.5) group, respectively. The number of injections and percentage of visits with active lesions were higher in GVE through 36 months. CONCLUSIONS:The mean VA of GVE tends to drop, but it is still much higher than NGVE eyes at 12, 24, and 36 months. Early detection and prompt treatment are key and should be considered in treatment access policies, regulatory frameworks, and clinical guidelines, as defining a threshold to start treatment may have a clear impact on final visual function, patient autonomy and legal blindness rates in nAMD patients.

Age-related Macular Degeneration (AMD) is the leading cause of blindness in the elderly, with its neovascular form characterised by abnormal vessel growth. Current anti-VEGF therapies require frequent intravitreal injections and show variable efficacy. Faricimab, a novel bispecific antibody targeting VEGF-A and ANG-2, offers a dual mechanism with the potential for enhanced efficacy and extended dosing intervals. This study aimed to characterise the intravitreal pharmacokinetics, biodistribution, and ocular localization of faricimab in a rat model of laser-induced choroidal neovascularization (CNV) using non-invasive molecular imaging. Faricimab was conjugated with DFO and radiolabelled with zirconium-89 ([89Zr]Zr-DFO-faricimab), maintaining functional binding to VEGF-A and ANG-2. Following intravitreal injection, pharmacokinetics was assessed by PET/CT, blood sampling, and autoradiography, alongside structural retinal evaluation by OCT. Both healthy and CNV-induced rats demonstrated biphasic ocular clearance with similar half-lives, obtaining no significant differences (Control AUC₀-∞ = 5587.3 ± 1419.3%·hour and AMD AUC₀-∞ = 4079.1 ± 1178.6%·hour). Autoradiography confirmed predominant retention in the posterior segment, with AMD eyes showing higher early accumulation, suggesting altered diffusion, and increased retinal binding. Whole-body biodistribution revealed systemic uptake primarily in the liver and spleen, consistent with antibody catabolism. This work represents the first study to report pharmacokinetic data of faricimab as well as its intraocular distribution in an AMD model. Our findings support its therapeutic potential and highlight PET imaging as a powerful non-invasive tool for longitudinal ocular pharmacokinetic studies.

Choroidal neovascularization (CNV) and inflammation play an important role in retinal disease development and the acute phase reactant C-reactive protein (CRP) has been shown to contribute to Age-related macular degeneration (AMD) in vitro. Our aim was to evaluate whether monomeric and pentameric CRP (pCRP, mCRP) isoforms contribute to CNV in vivo and to characterize the mechanism of CRP dissociation in-vivo and in vitro. Both CRP isoforms were intravitreally (IVT) or intravenously (IV) injected in mice, CNV was laser-induced, retinography and fluorescein angiography were performed to evaluate edema. Lectin, mCRP, F4/80 and C5b9 localization were assessed by immunofluorescence and visualized under a confocal microscope. CNV, intensity of fluorescence of mCRP (IF mCRP) was also quantified. To confirm pCRP dissociation in RPE cells and mice, pCRP was coupled to a fluorochrome and IVT injected. A statistical increase in CNV areas was observed in pCRP IVT injected males (p < 0.05) while a statistical decrease was shown in females (p < 0.05). After IV injection, pCRP males showed an increase in CNV areas only vs. mCRP injected mice (p < 0.05) and in females the injection of pCRP injected mice showed higher CNV areas vs. vehicle (p < 0.05) and vs. mCRP injected mice (p < 0.05). Retinal edema after IVT CRP injection was observed mainly in mCRP injected mice. In females there was an IF mCRP statistical decrease in pCRP IVT injected mice vs. vehicle and a statistical increase in pCRP IV injected mice vs. vehicle (p < 0.05). Mice injected with IVT isoforms showed F4/80 positive cells and C5b-9 deposition around the CNV areas. mCRP labeling was observed in the intercellular space of the endothelial cells in the angiogenic area and detected in pCRP IVT injected animals, demonstrating the dissociation of pCRP into mCRP both in vitro and in vivo in proinflammatory microenvironments. In conclusion, CRP administration increased the area of CNV and the edema observed in the subretinal space, suggesting that CRP is activated in the CNV inflammatory environment. In addition, we demonstrated that pCRP dissociates in vivo into mCRP in damaged areas close to CNV, hypothesizing that the CNV process is exacerbated by mCRP.

Introduction: New anti-vascular endothelial growth factor (VEGF) treatments are emerging for the treatment of diabetic macular edema (DME)/neovascular age-related macular degeneration (nAMD). This study aimed to explore the treatment attributes patients find important when deciding on treatment options. Methods: This noninterventional survey study assessed treatment preferences through a discrete choice experiment (DCE) among patients with DME/nAMD in the USA, Canada, France, Italy, Spain, and the UK. The DCE design was informed by a targeted literature review and qualitative interview research and included five treatment attributes: mode of administration, frequency of examinations, frequency of injections or refills, likely change in visual acuity, and eye-related side effects. Conditional logit models were used to analyze the choice data. Results: Overall, 537 patients completed the DCE (DME, n = 173; nAMD, n = 364). Patients reported preferring “injection” over “implant surgery and refills” and better visual outcomes over “stabilization,” which were also the most important attributes driving preference (35.1% and 31.5%, respectively). They also showed a preference for less-frequent treatment and examinations and for “mild-moderate, frequent” over “severe, rare” side effects. These findings were generally consistent across the two conditions, although significant differences were found depending on anti-VEGF treatment duration (nAMD, DME) and number of reported barriers (nAMD). Conclusion: Patient preferences for treatment are driven by several factors. Considering these preferences is essential when designing/introducing new therapies. Individual treatment preferences should be identified and given key consideration when helping patients select from an expanding array of treatment options.

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are common retinal diseases responsible for most blindness in working-age and elderly populations. Oxidative stress and mitochondrial dysfunction play roles in these pathogenesis, and new therapies counteracting these contributors could be of great interest. Some molecules, like coenzyme Q10 (CoQ10), are considered beneficial to maintain mitochondrial homeostasis and contribute to the prevention of cellular apoptosis. We investigated the impact of adding CoQ10 (Q) to a nutritional antioxidant complex (Nutrof Total®; N) on the mitochondrial status and apoptosis in an in vitro hydrogen peroxide (H2O2)-induced oxidative stress model in human retinal pigment epithelium (RPE) cells. H2O2 significantly increased 8-OHdG levels (p < 0.05), caspase-3 (p < 0.0001) and TUNEL intensity (p < 0.01), and RANTES (p < 0.05), caspase-1 (p < 0.05), superoxide (p < 0.05), and DRP-1 (p < 0.05) levels, and also decreased IL1β, SOD2, and CAT gene expression (p < 0.05) vs. control. Remarkably, Q showed a significant recovery in IL1β gene expression, TUNEL, TNFα, caspase-1, and JC-1 (p < 0.05) vs. H2O2, and NQ showed a synergist effect in caspase-3 (p < 0.01), TUNEL (p < 0.0001), mtDNA, and DRP-1 (p < 0.05). Our results showed that CoQ10 supplementation is effective in restoring/preventing apoptosis and mitochondrial stress-related damage, suggesting that it could be a valid strategy in degenerative processes such as AMD or DR.

Background: The objective of this study was to evaluate the association of the presence of conjunctival ultraviolet autofluorescence (CUVAF) with the level and progression of myopia and the impact of reduced sunlight exposure during the COVID-19 pandemic confinement (PC). Methods: A retrospective observational study was carried out using three cohorts, children (9–17 years old), young adults (18–25 years old), and adults (>40 years old) with myopia (≤0.75D) and at least three annual eye examinations (before and after PC). All participants underwent an automatic objective refraction and CUVAF area analysis. All the participants filled out a questionnaire regarding lifestyle and myopia history. Results: The 298 recruited participants showed that during the PC, children’s and young adults' myopia progression rate increased on average by −0.50 and −0.30 D/year, respectively, compared with the pre-pandemic level (p < 0.0001 and p < 0.01). A significantly greater progression was observed in those with low baseline myopia compared to those with moderate or high myopia (p < 0.01). CUVAF shows its protective effect associated with outdoor activity (OA) with regard to the age of onset of myopia and mean diopters (p < 0.01). In fact, although there were no differences in the increase in diopters between children with and without CUVAF during the PC, those who had CUVAF started with lower gains (−0.3 D/year) compared to those who did not (−0.5 D/year; p < 0.05). The myopia treatments (atropine drops, Ortho-K, and MiSight® contact lenses) showed a reduction effect in myopic progression rate post-PC in comparison with non-treated children (p < 0.0001, p < 0.0001 and p < 0.01, respectively). Conclusions: The strict restriction of OA during PC led to the rate of myopia progression doubling among children and young adults. This progression occurred mainly in children with previously low myopia, and CUVAF, as a biomarker of OA, reflects its potential to provide benefits in the form of recommended behavioral changes to protect against the development of myopia.

Aims/Purpose: Increased systemic levels of the acute phase reactant C‐reactive protein (CRP) have been linked to increased risk of age‐related macular degeneration (AMD). CRP undergoes conformational changes upon activation in inflammatory microenvironments between pentameric (pCRP) and monomeric forms (mCRP). CRP conformations present different phenotypes, as mCRP has more proinflammatory properties and has been shown to induce blood retinal barrier disruption in vitro. Thus, we aimed to evaluate the impact of CRP forms on choroidal neovascularization (CNV) in vivo. Methods: pCRP and mCRP forms were intravenously (iv) or intravitreally (ivt) injected in C57BL6/J mice ( n = 12) previously subjected to CNV induction by laser and compared to controls. CNV lesions were monitored by fluorescein angiography and mice were euthanized 11 days after lesion induction. CNV areas were measured in lectin stained choroidal flatmounts. To evaluate the CRP dissociation, pCRP was coupled to a fluorescent molecule before injection. After tissue extraction mCRP was detected by immunofluorescence in posterior pole flatmounts. Results: Both pCRP and mCRP injected significantly increased CNV areas compared to control mice. Retinal severe edema was also observed close to the lesion in retinographies, and was more severe in intravitreally injected groups. Finally, pCRP was observed to dissociate into mCRP in intravitreally injected animals with pCRP. Conclusions: We confirmed that CRP increases CNV areas and severe edema in the retina, suggesting that CRP is activated in the CNV inflammatory environment. Additionally, the pCRP form dissociates in vivo into mCRP close to CNV damaged tissue, hypothesizing that mCRP is the CRP conformation that contributes to the exacerbation of the CNV process. Further studies are needed to investigate anti‐mCRP molecules as candidates for mono‐ or anti‐VEGF combined therapy for AMD treatments.

To estimate the economic impact for the society, generated as a consequence of the onset of loss of vision and irreversible legal blindness, for the main ophthalmologic diseases in Spain: glaucoma, diabetic retinopathy (DR), diabetic macular edema (DME), age-related macular degeneration (AMD) and high myopia (HM). A cost analysis model was developed to estimate the economic burden of glaucoma, DR, DME, AMD and HM over a 10-year time horizon (2021-2030), from a societal perspective in Spain. The epidemiological and economic parameters used in the model were obtained through a literature review. Prevalence, incidence, and progression stages were used to establish the epidemiological flows. Annual costs per patient from publications were included and classified into direct healthcare, direct non-healthcare and indirect costs. Costs from other countries were converted based on purchasing-power-parity (€EUR, PPP). Epidemiological parameters about population and cost results were validated by a panel of experts. All costs were adjusted to euros, 2021 (€, 2021), and using the Consumer Price Index (CPI) of the last 10 years, extrapolated to 2030 euros (€, 2030). It was estimated that the total population of patients with the main diseases pathologies (glaucoma, DR, DME, AMD and HM) will increase to 7.99 million patients by 2030, representing an increase of 103

Introduction: Understanding patient perspectives of treatment may improve adherence and outcomes. This study explored real-world patient experiences with anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD). Methods: This multinational, non-interventional, quantitative, cross-sectional, observational survey assessed treatment barriers/burden, patient-reported visual functioning, and treatment satisfaction in DME and nAMD patients in the United States, United Kingdom, Canada, France, Italy, and Spain. Treatment patterns and visual outcomes were extracted from medical charts. Regression models evaluated relationships between adherence, total missed visits, number of anti-VEGF injections and clinical and patient-reported outcomes for visual functioning. Association between treatment satisfaction and aspects of burden were assessed. Results: The survey was completed by 183 DME and 391 nAMD patients. Patients had moderately high vision-related functioning (25-item National Eye Institute Visual Functioning Questionnaire score: mean=74.8) and were satisfied with their current treatment (mean total score: Macular Disease Treatment Satisfaction Questionnaire=59.2; Retinopathy Treatment Satisfaction Questionnaire=61.3). Treatment satisfaction scores were worse with higher time-related impacts of treatment (nAMD/DME), higher impacts on finances and daily life (nAMD), negative impact on employment and lower expectations for treatment effectiveness (DME). Most patients reported ≥1 barrier (66.1% DME, 49.2% nAMD patients) related to treatment (35.0%), clinic (32.6%), and COVID-19 (21.1%). Moreover, 44.9% of patients reported some impairment in activities of daily living. Work absenteeism was observed among >60% of working patients. Nearly one-quarter (24.2%) of patients needed ≥1 day to recover from intravitreal injections; most reported ≥30 minutes of travel time (73.7%) and clinic wait time (54.2%). In unadjusted univariable analyses, treatment adherence (vs non adherence) was related to higher most recent visual acuity (β = 8.98 letters; CI, 1.34–16.62) and lower odds of visual acuity below driving vision (≤ 69 letters) (OR = 0.50; CI, 0.25–1.00) . Conclusion: More durable treatments with reduced frequency of injections/visits may reduce treatment burden and improve patient satisfaction, which may enhance adherence and visual outcomes.

IntroductionThe prevalence of myopia has increased significantly in recent years including an earlier onset of myopia development on the pediatric population. The main objective of the study is to compare CUVAF (Conjunctival Ultraviolet Autofluorescence) in children with and without myopia to validate its usefulness as an outdoor protective biomarker.MethodsA case–control observational study was conducted in a child cohort from subjects that attended to the Ophthalmology Department of Clínica Universidad de Navarra for an ophthalmological examination. The general exclusion criteria were (among others): amblyopia, congenital myopia, general ophthalmic disease, and any conjunctival alteration that might difficult the measurement of the CUVAF area. All participants underwent an automatic objective refraction under cycloplegic effect, biometry to measure axial length (AL) and central corneal radius (CCR), and completed a questionnaire about their lifestyle habits. A total of 4 images of the bulbar conjunctiva were taken with blue light in order to quantify the CUVAF area.ResultsA total of 263 subjects (6 to 17 years old) were analyzed with no significant differences in demographic data between case group and control group. There were 50 non-myopic subjects (19%) and 213 myopic subjects (81%). In relation to the outdoor activities (OA), myopic subjects spent significantly fewer hours per week outdoors than the control-group (p = 0.03). About the CUVAF area, the differences between groups were statistically significant, showing that the myopic group has a significantly smaller CUVAF area than the control-group (0.33 ± 0.72 mm2 vs. 0.78 ± 1.22 mm2; p = 0.0023), likewise, the frequency of CUVAF area absence between both groups showed an odds ratio (OR) of 2.52 (CI95% 1.33–4.74). A Pearson correlation test was done, obtaining a strong significant inverse correlation between myopia degree-CUVAF area (r = 0.1877; IC95% 0.068–0.302), and also ratio (AL/CCR)-CUVAF area (p = 0.002 and p = 0.04) respectively.ConclusionCUVAF is a useful biomarker for OA and it has an inverse relationship with myopia degree also in pediatric age, especially after the age of 12, so it could be useful to differentiate the risk of developing myopia. Having a CUVAF area greater than that corresponding to age, protect to myopia 2.5 times, being almost 5 times the protection in case of high myopia.

Age-related macular degeneration (AMD) is a leading cause of severe vision loss in older individuals in developed countries. Despite advances in our understanding of AMD, its pathophysiology remains poorly understood. Matrix metalloproteinases (MMPs) have been proposed to play a role in AMD development. In this study, we aimed to characterize MMP-13 in AMD. We used retinal pigment epithelial cells, a murine model of laser-induced choroidal neovascularization, and plasma samples from patients with neovascular AMD to conduct our study. Our results show that MMP13 expression significantly increased under oxidative stress conditions in cultured retinal pigment epithelial cells. In the murine model, MMP13 was overexpressed in both retinal pigment epithelial cells and endothelial cells during choroidal neovascularization. Additionally, the total MMP13 levels in the plasma of patients with neovascular AMD were significantly lower than those in the control group. This suggests a reduced diffusion from the tissues or release from circulating cells in the bloodstream, given that the number and function of monocytes have been reported to be deficient in patients with AMD. Although more studies are needed to elucidate the role of MMP13 in AMD, it could be a promising therapeutic target for treating AMD.

Exposure to blue light has seriously increased in our environment since the arrival of light emitting diodes (LEDs) and, in recent years, the proliferation of digital devices rich in blue light. This raises some questions about its potential deleterious effects on eye health. The aim of this narrative review is to provide an update on the ocular effects of blue light and to discuss the efficiency of methods of protection and prevention against potential blue light-induced ocular injury. The search of relevant English articles was conducted in PubMed, Medline, and Google Scholar databases until December 2022. Blue light exposure provokes photochemical reactions in most eye tissues, in particular the cornea, the lens, and the retina. In vitro and in vivo studies have shown that certain exposures to blue light (depending on the wavelength or intensity) can cause temporary or permanent damage to some structures of the eye, especially the retina. However, currently, there is no evidence that screen use and LEDs in normal use are deleterious to the human retina. Regarding protection, there is currently no evidence of a beneficial effect of blue blocking lenses for the prevention of eye diseases, in particular age-related macular degeneration (AMD). In humans, macular pigments (composed of lutein and zeaxanthin) represent a natural protection by filtering blue light, and can be increased through increased intake from foods or food supplements. These nutrients are associated with lower risk for AMD and cataract. Antioxidants such as vitamins C, E, or zinc might also contribute to the prevention of photochemical ocular damage by preventing oxidative stress. Currently, there is no evidence that LEDs in normal use at domestic intensity levels or in screen devices are retinotoxic to the human eye. However, the potential toxicity of long-term cumulative exposure and the dose-response effect are currently unknown.

Objective To assess the effectiveness and safety of the intravitreal fluocinolone-acetonide implant (FAc-i) in patients with chronic diabetic macular edema who did not sufficiently respond to other available therapies. Methods This was a multicenter, prospective, non-randomized, and phase-IV observational study conducted on patients with recurrent-DME who were insufficient responders to currently available therapies (REACT-Study). The primary end-point was the mean change in best-corrected-visual-acuity from baseline to month-24 values. Results Thirty-one eyes from 31 patients were included in the study. Mean age was 68.0 ± 7.7 years, and 10 (32.3%) were women. Study patients had received 5.3 ± 7.3 previous DME treatments before starting the study. In the overall study sample, BCVA improved from 56.1 ± 12.3 letters at baseline to 62.4 ± 17.0 letters at month-24 ( p = 0.0510). The eyes with a baseline BCVA < 70 ETDRS letters had a significant improvement in BCVA from 53.2 ± 10.2 letters at baseline to 61.5 ± 17.9 letters at month-24 ( p = 0.0165). In the overall study population, central-subfoveal-thickness (CST) was significantly reduced from 474.0 ± 135.1 µm at baseline to 333.4 ± 135.6 at month-24 ( p < 0.0001). Similarly, macular-volume (MV) was significantly reduced from 10.7 ± 2.7 mm 3 at baseline to 9.6 ± 2.9 mm 3 ( p = 0.0027) at month-24. Among the 31 study eyes, 19 (61.3%) required an additional treatment for DME. Throughout the study, 9 (29.0%) eyes required ocular hypotensive medication for controlling their intraocular-pressure and 5 (16.1%) eyes underwent cataract surgery. Conclusions In DME eyes who did not sufficiently respond to previous therapies, the FAc-i was associated with an improvement in visual and anatomic outcomes. There were no unexpected adverse-events. Trial registration number EudraCT identifier: 2016-001680-37.