Assessment of the predictive ability of theranostics for corneal cross-linking in treating keratoconus: a randomized clinical trial.

PURPOSE: To validate the ability of theranostic imaging biomarkers in assessing the propensity of corneal cross-linking (CXL) in flattening the maximum keratometry (Kmax) index. DESIGN: Prospective, randomized, multicenter, masked clinical trial (NCT05457647). PARTICIPANTS: Fifty patients with progressive keratoconus. INTERVENTION: Participants were stratified to undergo epithelium-off (epi-off; 25 eyes) and epithelium-on (epi-on; 25 eyes) CXL protocols using UV-A medical device incorporating theranostic software module. The device used controlled UV-A light both for performing CXL and for estimating the corneal riboflavin concentration (riboflavin score) and assessing treatment effect (theranostic score) in real time. A 0.22% riboflavin formulation was applied onto the cornea for 15 minutes and 20 minutes in epi-off and epi-on protocols respectively. All eyes underwent 9 minutes UV-A irradiance at 10 mW/cm2. MAIN OUTCOME MEASURES: The primary outcome measure was validation of the combined use of theranostic imaging biomarkers through measurement of their accuracy (proportion of correctly classified eyes) and precision (positive predictive value) to correctly classify eyes and positively predict a Kmax flattening at 1 year after CXL. Other outcome measures were the change of Kmax, endothelial cell density, uncorrected and corrected distance visual acuity, manifest spherical equivalent refraction, and central corneal thickness one year after CXL. RESULTS: Accuracy and precision of the combined use of theranostic imaging biomarkers in predicting eyes that had more than 0.1 diopter (D) Kmax flattening at 1 year were 91% and 95% respectively. The Kmax value significantly flattened by a median of -1.3 D (IQR: -2.11, -0.49 D; P < 0.001); both the uncorrected and corrected distance visual acuity improved by a median of -0.1 LogMAR (IQR: -0.3, 0.0 LogMAR; P < 0.001 and IQR: -0.2, 0.0 LogMAR; P < 0.001 respectively). There were no significant changes in endothelial cell density (P = 0.33) and central corneal thickness (P = 0.07) 1 year postoperatively. CONCLUSIONS: The study demonstrated the efficacy of integrating theranostics in a UV-A medical device for the precise and predictive treatment of keratoconus with epi-off and epi-on CXL protocols. The concentration of riboflavin and its UV-A light mediated photo-activation in the cornea are the primary factors determining CXL treatment efficacy.

Spatial targeted delivery of riboflavin with a controlled corneal iontophoresis delivery system in theranostic-guided UV-A light photo-therapy.

Seven human donor eye globes underwent corneal cross-linking using theranostic UV-A device with accessory corneal iontophoresis system for patterned delivery of a 0.22% riboflavin solution. Theranostic-guided UV-A light illumination assessed riboflavin distribution and treated corneas at 10 mW/cm2 for 9 min with a 5.0-mm beam size. Corneal topography maps were taken at baseline and 2-h post-treatment. Analysis utilized corneal topography elevation data, with results showing controlled riboflavin delivery led to a consistent gradient, with 40% higher levels centrally (248 ± 79 µg/cm3) than peripherally (180 ± 72 µg/cm3 at ±2.5 mm from the center). Theranostic-guided UV-A light irradiation resulted in significant changes in corneal topography, with a decrease in best-fit sphere value (-0.7 ± 0.2 D; p < 0.001) and consistent downward shift in corneal elevation map (-11.7 ± 3.7 µm). The coefficient of variation was 2.5%, indicating high procedure performance in achieving significant and reliable corneal flattening.

Targeted next-generation sequencing analysis in Italian patients with keratoconus.

OBJECTIVE: To report variants in 26 candidate genes and describe the clinical features of Italian patients with keratoconus (KC). SUBJECTS/METHODS: Sixty-four patients with a confirmed diagnosis of KC were enrolled in this genetic association study. Patients were classified into two study groups according to whether they had a confirmed diagnosis of progressive or stable KC. A purpose-developed Next Generation Sequencing (NGS) panel was used to identify and analyse the coding exons and flanking exon/intron boundaries of 26 genes known to be associated with KC and corneal dystrophies. Interpretation of the pathogenic significance of variants was performed using in silico predictive algorithms. RESULT: The targeted NGS research identified a total of 167 allelic variants of 22 genes in the study population; twenty-four patients had stable keratoconus (n. 54 variants) and forty patients had progressive disease (n. 113 variants). We identified genetic variants of certain pathogenic significance in five patients with progressive KC; in addition, eight novel genetic variants were found in eight patients with progressive KC. Mutations of FLG, LOXHD1, ZNF469, and DOCK9 genes were twice more frequently identified in patients with progressive than stable disease. Filaggrin gene variants were found in 49 patients (76% of total), of whom 32 patients (80% of progressive KC group) had progressive disease. CONCLUSIONS: Targeted NGS research provided new insights into the causative effect of candidate genes in the clinical phenotype of keratoconus. Filaggrin mutations were found to represent a genetic risk factor for development of progressive disease in Italy.

Short Wavelength Automated Perimetry, Standard Automated Perimetry, and Optical Coherence Tomography in Dominant Optic Atrophy.

Background: Blue-yellow axis dyschromatopsia is well-known in Autosomal Dominant Optic Atrophy (ADOA) patients, but there were no data on the correlation between retinal structure and short-wavelength automated perimetry (SWAP) values in this pathology. Methods: In this cross-sectional case-control study, we assessed the correlation between best corrected visual acuity (BCVA), standard automated perimetry (SAP), SWAP, and optical coherence tomography (OCT) parameters of 9 ADOA patients compared with healthy controls. Correlation analysis was performed between BCVA, mean deviation, pattern standard deviation (PSD), and fovea sensitivity (FS) values and the OCT thickness of each retinal layer and the peripapillary retinal nerve fiber layer (pRNFL). Results: The following significant and strong correlations were found: between BCVA and ganglion cell layer (GCL) and the global (G) pRNFL thicknesses; between SAP FS and GCL and the G-pRNFL thicknesses; between SWAP PSD and total retina, GCL, inner plexiform layer, inner nuclear layer, inner retinal layer and the temporal pRNFL thicknesses. We found a constant shorter duration of the SITA-SWAP compared with the SITA-STANDARD strategy. Conclusions: SWAP, SAP, and BCVA values provided relevant clinical information about retinal involvement in our ADOA patients. The perimetric functional parameters that seemed to correlate better with structure involvement were FS on SAP and PSD on SWAP.

Estimated prevalence of keratoconus in the largest metropolitan area of Italy.

PURPOSE: To estimate the prevalence of keratoconus in a population of subjects undergoing first eye examination in an eye clinic in Italy. METHODS: A single-center, cross-sectional, study was conducted involving patients who underwent first eye examination at an eye clinic in Rome between September 2021 and June 2022. The prevalence of keratoconus was determined by Placido-disk corneal topography using the maximum keratometry (Kmax) value and the Cone Magnitude and Location Index (CLMI) for keratoconus screening. Subjective analysis was performed by two experienced corneal specialists, who classified the outcome into two groups: normal and keratoconus. Risk factors, including family history of keratoconus, allergy or atopy, thyroid disease, eye rubbing habit and gender were also examined. RESULTS: A total of 512 subjects between 7 and 81 years old were evaluated. The inter-observer agreement to classify subjects in normal or keratoconus group was excellent (k = 1.0); the estimated prevalence in the specific population was 2.1%. Presence of positive family history (9% of keratoconus vs 5% normal), concomitant allergy or atopy (27% vs 9%) and eye rubbing habit (18% vs 4%) were associated with a higher risk of disease. CONCLUSION: This study reported a high estimated prevalence of keratoconus in a metropolitan area of Italy, as found in recent studies in the Mediterranean and Middle East countries. Screening for keratoconus is highly recommendable and easily feasible with corneal topography under expert supervision and may be indicated primarily in young population to improve early detection and prompt therapeutic management for halting disease progression.

Real-time monitoring of riboflavin concentration using different clinically available ophthalmic formulations for epi-off and epi-on corneal cross-linking.

PURPOSE: To assess the feasibility of theranostics to determine the riboflavin concentration in the cornea using clinically available ophthalmic formulations during epithelium-off (epi-off) and transepithelial (epi-on) corneal cross-linking procedures. METHODS: Thirty-two eye bank human donor corneas were equally randomized in eight groups; groups 1 to 3 and groups 4 to 8 underwent epi-off and epi-on delivery of riboflavin respectively. Riboflavin ophthalmic solutions were applied onto the cornea according to the manufacturers' instructions. The amount of riboflavin into the cornea was estimated, at preset time intervals during imbibition time, using theranostic UV-A device (C4V CHROMO4VIS, Regensight srl, Italy) and expressed as riboflavin score (d.u.). Measurements of corneal riboflavin concentration (expressed as µg/cm3) were also performed by spectroscopy absorbance technique (AvaLight-DH-S-BAL, Avantes) for external validation of theranostic measurements. RESULTS: At the end of imbibition time in epi-off delivery protocols, the average riboflavin score ranged from 0.77 ± 0.38 (the average corneal riboflavin concentration was 213 ± 190 µg/cm3) to 1.79 ± 0.07 (554 ± 103 µg/cm3). In epi-on delivery protocols, the average riboflavin score ranged from 0.17 ± 0.01 to 0.67 ± 0.19 (corneal riboflavin concentration ranged from 6 ± 5 µg/cm3 to 122 ± 39 µg/cm3) at the end of imbibition time. A statistically significant linear correlation (P ≤ 0.05) was found between the theranostic and spectrophotometry measurements in all groups. CONCLUSIONS: Real-time theranostic imaging provided an accurate strategy for assessing permeation of riboflavin into the human cornea during the imbibition phase of corneal cross-linking, regardless of delivery protocol. A large variability in corneal riboflavin concentration exists between clinically available ophthalmic formulations both in epi-off and epi-on delivery protocols.

Selective Hydrofunctionalization of N-Allenyl Derivatives with Heteronucleophiles Catalyzed by Brønsted Acids.

In this study, we present a novel and environmentally sustainable protocol for the γ-hydrofunctionalization of N-allenyl compounds using various heteronucleophiles catalyzed solely by simple Brønsted acids. The method displays remarkable attributes, highlighting its sustainability, efficiency, regio- and stereoselectivity, as well as its versatile applicability to diverse heteroatom-containing enamides. Notably, our approach eliminates the need for metal catalysts and toxic solvents, representing a significant advancement in greener chemistry practices. We demonstrate the broad scope of our protocol by successfully scaling up reactions to gram-scale syntheses, underscoring its robustness for potential industrial implementation. The resulting γ-heterosubstituted enamides offer new possibilities for further synthetic transformations, yielding highly functionalized compounds with diverse applications. Mechanistic investigations reveal the pivotal role of CSA as a catalyst, enabling alcohol addition via a covalent activation mode.

Non-Invasive High-Resolution Imaging of In Vivo Human Myelinated Axons.

This work aims to reveal the microscopic (2-3 micrometer resolution) appearance of human myelinated nerve fibers in vivo for the first time. We analyzed the myelinated retinal nerve fibers of a male patient without other neurological disorders in a non-invasive way using the transscleral optical phase imaging method with adaptive optics. We also analyzed the fellow eye with non-myelinated nerve fibers and compared the results with traditional ocular imaging methods such as optical coherence tomography. We documented the microscopic appearance of human myelin and myelinated axons in vivo. This method allowed us to obtain better details than through traditional ocular imaging methods. We hope these findings will be useful to the scientific community to evaluate neuro-retinal structures through new imaging techniques and more accurately document nerve anatomy and the pathophysiology of this disease.

Accuracy of an Air-Puff Dynamic Tonometry Biomarker to Discriminate the Corneal Biomechanical Response in Patients With Keratoconus.

PURPOSE: The aim of this study was to assess accuracy of the mean corneal stiffness ( kc , N/m) parameter to discriminate between patients with keratoconus and age-matched healthy subjects. METHODS: Dynamic Scheimpflug imaging tonometry was performed with Corvis ST (Oculus Optikgeräte GmbH, Germany) in patients with keratoconus (n = 24; study group) and age-matched healthy subjects (n = 32; control). An image processing algorithm was developed to analyze the video sequence of the Corvis ST air-puff event and to determine the geometric and temporal parameters that correlated with the corneal tissue biomechanical properties. A modified 3-element viscoelastic model was used to derive the kc parameter, which represented the corneal tissue resistance to deformation under load. Receiver operating characteristic curves were used to assess the overall diagnostic performance for determining the area under the curve, sensitivity, and specificity of the kc in assessing the corneal tissue deformation to the Corvis ST air-puff event in keratoconus and control eyes. The Corvis Biomechanical Index ( CBI ) was analyzed for external validation. RESULTS: The kc parameter was significantly different between keratoconus and controls ( P < 0.001), ranging from 24.9 ±3.0 to 34.2 ±3.5 N/m, respectively. It was highly correlated with CBI (r = -0.69; P < 0.001); however, the kc parameter had greater specificity (94%) than CBI (75%), whereas the 2 biomarkers had similar area under the curve (0.98 vs. 0.94) and sensitivity (96% vs. 92%) in predicting the occurrence of keratoconus. CONCLUSIONS: The kc parameter extracted by video processing analysis of dynamic Scheimpflug tonometry data was highly accurate in discriminating patients with clinically manifest keratoconus compared with controls.

Assessing Feasibility of Cognitive Impairment Testing Using Social Robotic Technology Augmented with Affective Computing and Emotional State Detection Systems.

Social robots represent a valid opportunity to manage the diagnosis, treatment, care, and support of older people with dementia. The aim of this study is to validate the Mini-Mental State Examination (MMSE) test administered by the Pepper robot equipped with systems to detect psychophysical and emotional states in older patients. Our main result is that the Pepper robot is capable of administering the MMSE and that cognitive status is not a determinant in the effective use of a social robot. People with mild cognitive impairment appreciate the robot, as it interacts with them. Acceptability does not relate strictly to the user experience, but the willingness to interact with the robot is an important variable for engagement. We demonstrate the feasibility of a novel approach that, in the future, could lead to more natural human-machine interaction when delivering cognitive tests with the aid of a social robot and a Computational Psychophysiology Module (CPM).

Stereoselective Synthesis of α-Disubstituted ß-Homoprolines.

An efficient enantioselective synthesis of chiral α-disubstituted ß-homoprolines was developed, starting with the stereodivergent allylation of chiral N-tert-butanesulfinyl imines derived from 4-bromobutanal with indium or zinc and using well-established and reliable synthetic transformations. This methodology allows the easy introduction of different substituents at the α-position of the pyrrolidine scaffold and is characterized by the possibility of switching the absolute configuration of the newly formed stereocenter either by changing the configuration of the tert-butanesufinamide chiral auxiliary or by using a different stereodivergent allylation protocol with the same auxiliary.

Paving the Way for Predicting the Progression of Cognitive Decline: The Potential Role of Machine Learning Algorithms in the Clinical Management of Neurodegenerative Disorders.

Alzheimer's disease (AD) is the most common form of neurodegenerative disorder. The prodromal phase of AD is mild cognitive impairment (MCI). The capacity to predict the transitional phase from MCI to AD represents a challenge for the scientific community. The adoption of artificial intelligence (AI) is useful for diagnostic, predictive analysis starting from the clinical epidemiology of neurodegenerative disorders. We propose a Machine Learning Model (MLM) where the algorithms were trained on a set of neuropsychological, neurophysiological, and clinical data to predict the diagnosis of cognitive decline in both MCI and AD patients. METHODS: We built a dataset with clinical and neuropsychological data of 4848 patients, of which 2156 had a diagnosis of AD, and 2684 of MCI, for the Machine Learning Model, and 60 patients were enrolled for the test dataset. We trained an ML algorithm using RoboMate software based on the training dataset, and then calculated its accuracy using the test dataset. RESULTS: The Receiver Operating Characteristic (ROC) analysis revealed that diagnostic accuracy was 86%, with an appropriate cutoff value of 1.5; sensitivity was 72%; and specificity reached a value of 91% for clinical data prediction with MMSE. CONCLUSION: This method may support clinicians to provide a second opinion concerning high prognostic power in the progression of cognitive impairment. The MLM used in this study is based on big data that were confirmed in enrolled patients and given a credibility about the presence of determinant risk factors also supported by a cognitive test score.

Putting a "C60 Ball" and Chain to Chlorin e6 Improves Its Cellular Uptake and Photodynamic Performances.

Chlorin e6 (Ce6) and fullerene (C60) are among the most used photosensitizers (PSs) for photodynamic therapy (PDT). Through the combination of the chemical and photophysical properties of Ce6 and C60, in principle, we can obtain an "ideal" photosensitizer that is able to bypass the limitations of the two molecules alone, i.e., the low cellular uptake of Ce6 and the scarce solubility and absorption in the red region of the C60. Here, we synthesized and characterized a Ce6-C60 dyad. The UV-Vis spectrum of the dyad showed the typical absorption bands of both fullerene and Ce6, while a quenching of Ce6 fluorescence was observed. This behavior is typical in the formation of a fullerene-antenna system and is due to the intramolecular energy, or electron transfer from the antenna (Ce6) to the fullerene. Consequently, the Ce6-C60 dyad showed an enhancement in the generation of reactive oxygen species (ROS). Flow cytometry measurements demonstrated how the uptake of the Ce6 was strongly improved by the conjugation with C60. The Ce6-C60 dyad exhibited in A431 cancer cells low dark toxicity and a higher PDT efficacy than Ce6 alone, due to the enhancement of the uptake and the improvement of ROS generation.

Recent Advances in Asymmetric Synthesis of Pyrrolidine-Based Organocatalysts and Their Application: A 15-Year Update.

In 1971, chemists from Hoffmann-La Roche and Schering AG independently discovered a new asymmetric intramolecular aldol reaction catalyzed by the natural amino acid proline, a transformation now known as the Hajos-Parrish-Eder-Sauer-Wiechert reaction. These remarkable results remained forgotten until List and Barbas reported in 2000 that L-proline was also able to catalyze intermolecular aldol reactions with non-negligible enantioselectivities. In the same year, MacMillan reported on asymmetric Diels-Alder cycloadditions which were efficiently catalyzed by imidazolidinones deriving from natural amino acids. These two seminal reports marked the birth of modern asymmetric organocatalysis. A further important breakthrough in this field happened in 2005, when Jørgensen and Hayashi independently proposed the use of diarylprolinol silyl ethers for the asymmetric functionalization of aldehydes. During the last 20 years, asymmetric organocatalysis has emerged as a very powerful tool for the facile construction of complex molecular architectures. Along the way, a deeper knowledge of organocatalytic reaction mechanisms has been acquired, allowing for the fine-tuning of the structures of privileged catalysts or proposing completely new molecular entities that are able to efficiently catalyze these transformations. This review highlights the most recent advances in the asymmetric synthesis of organocatalysts deriving from or related to proline, starting from 2008.

Predicting corneal cross-linking treatment efficacy with real-time assessment of corneal riboflavin concentration.

PURPOSE: To assess predictability of tissue biomechanical stiffening induced by UV-A light-mediated real-time assessment of riboflavin concentration during corneal crosslinking (CXL) of human donor tissues. SETTING: Studio Italiano di Oftalmologia, Rome, Italy. DESIGN: Laboratory study. METHODS: 20 sclerocorneal tissues were randomly stratified to undergo CXL with either the epithelium intact (n = 12) or removed (n = 8). Samples underwent corneal soaking with 0.22% riboflavin formulation (RitSight) with dosing time of t = 10 minutes and t = 20 minutes in epithelium-off and epithelium-on protocols, respectively. All tissues underwent 9-minute UV-A irradiance at 10 mW/cm 2 using theranostic device (C4V CHROMO4VIS). The device used controlled UV-A light irradiation to induce both imaging and treatment of the cornea, providing a real-time measure of corneal riboflavin concentration and treatment efficacy (ie, theranostic score) during surgery. Tissue biomechanics were assessed with an air-puff device (Corvis), which was performed before and after treatment. A 3-element viscoelastic model was developed to fit the corneal deformation response to air-puff excitation and to calculate the mean corneal stiffness parameter (k c ). RESULTS: Significant corneal tissue stiffening ( P < .05) was induced by the theranostic UV-A device in either CXL treatment protocol. Significant correlation was found between the theranostic score and the increase in k c ( R = 0.75; P = .003). The score showed high accuracy (94%) and precision (94%) to predict correctly samples that had improved tissue biomechanical strengthening. CONCLUSIONS: Real-time assessment of corneal riboflavin concentration provided a predictive and precise approach for significant improvement of tissue strength on individual corneas, regardless of CXL treatment protocol.

Long-Term Zonal Average Analysis of Corneal Tomography in Keratoconus Eyes.

PURPOSE: The scope of this study was to investigate keratoconus progression using zonal average analysis of corneal tomography. METHODS: The corneal tomographies of patients participating in initial baseline and all scheduled follow-up visits up to 4 years were analyzed. Data were exported in custom software, which delineated 4 zones of analysis and calculated the average values of the anterior and posterior curvature and the average thickness for each zone at each visit. In particular, a 3.1 mm 2 area containing the K max , termed "keratoconus cone zone," was defined for assessing disease progression during the follow-up. RESULTS: A total of 201 patients were enrolled in this prospective study. At 4 years, 31% of the eyes (n = 62) had an average increase of ≥1.0 D in the keratoconus cone zone in baseline visit, whereas only 11% of the eyes (n = 22) had ≥1.0 D K max increase in the same period. The zonal anterior average curvature (+1.1 D; P < 0.001) and thickness (-14 µm; P < 0.001) values of the keratoconus cone zone progressed significantly during the follow-up. A high correlation was found between the 4-year changes of K max and central corneal thickness values and the change of the average anterior curvature and thickness values in the keratoconus cone zone. The posterior cornea did not show significant average changes (<-0.2 D; P > 0.05) during the follow-up. CONCLUSIONS: Single-point tomography indexes for keratoconus progression did not capture the overall structure and shape changes of the cornea. It would be recommended to update criteria for keratoconus management including the zonal average analysis of curvature and thickness values for tracking disease progression over observation periods longer than 1 year.

A randomized clinical trial assessing theranostic-guided corneal cross-linking for treating keratoconus: the ARGO protocol.

The Assessment of theranostic guided riboflavin/UV-A corneal cross-linking for treatment of keratoconus (ARGO; registration number NCT05457647) clinical trial tests the hypothesis that theranostic-guided riboflavin/UV-A corneal cross-linking (CXL) can provide predictable clinical efficacy for halting keratoconus progression, regardless of treatment protocol, i.e., either with or without epithelial removal. Theranostics is an emerging therapeutic paradigm of personalized and precision medicine that enables real-time monitoring of image-guided therapy. In this trial, the theranostic software module of a novel UV-A medical device will be validated in order to confirm its accuracy in estimating corneal cross-linking efficacy in real time. During CXL procedure, the theranostic UV-A medical device will provide the operator with an imaging biomarker, i.e., the theranostic score, which is calculated by non-invasive measurement of corneal riboflavin concentration and its UV-A light mediated photo-degradation. ARGO is a randomized multicenter clinical trial in patients aged between 18 and 40 years with progressive keratoconus aiming to validate the theranostic score by assessing the change of the maximum keratometry point value at 1-year postoperatively. A total of 50 participants will be stratified with allocation ratio 1:1 using a computer-generated stratification plan with blocks in two treatment protocols, such as epithelium-off or epithelium-on CXL. Following treatment, participants will be monitored for 12 months. Assessment of safety and performance of theranostic-guided corneal cross-linking treatment modality will be determined objectively by corneal tomography, corneal endothelial microscopy, visual acuity testing and slit-lamp eye examination.

Theranostic-guided corneal cross-linking: Preclinical evidence on a new treatment paradigm for keratoconus.

Theranostics is an emerging therapeutic paradigm of personalized medicine; the term refers to the simultaneous integration of therapy and diagnostics. In this work, theranostic-guided corneal cross-linking was performed on 10 human sclero-corneal tissues. The samples were soaked with 0.22% riboflavin formulation and underwent 9 minutes UV-A irradiance at 10 mW/cm2 using theranostic device, which provided both a measure of corneal riboflavin concentration and a theranostic score estimating treatment efficacy in real time. A three-element viscoelastic model was developed to fit the deformation response of the cornea to air-puff excitation of dynamic tonometry and to calculate the mean corneal stiffness parameter before and after treatment. Significant correlation was found between the theranostic score and the increase in mean corneal stiffness (R = 0.80; P < .001). Accuracy and precision of the theranostic score in predicting the induced corneal tissue stiffening were both 90%. The riboflavin concentration prior to starting the UV-A photo-therapy phase was the most important variable to allow corneal cross-linking to be effective. Theranostic UV-A light mediated imaging and therapy enables the operator to adopt a precise approach for achieving highly predictable biomechanical strengthening on individual corneas.

Challenges in Age-Related Macular Degeneration: From Risk Factors to Novel Diagnostics and Prevention Strategies.

Age-related macular degeneration (AMD) is a chronic multifactorial eye disease representing the primary cause of vision loss in people aged 60 years and older. The etiopathogenesis of the disease remains uncertain, with several risk factors contributing to its onset and progression, such as genotype, aging, hypertension, smoking, overweight, and low dietary intake of carotenoids. Since the aging populations of the industrialized world are increasing rapidly, the impact of AMD in the socio-economical life-developed countries is expected to increase dramatically in the next years. In this context, the benefits of prevention and early disease detection for prompt and effective treatment can be enormous to reduce the social and economic burden of AMD. Nutritional and lifestyle changes, including dietary intake of xanthophyll pigments, such as lutein and zeaxanthin, no smoking, and regular exercise, are known to protect from risk of AMD progression from early to advanced disease stages. In this review, we present the clinical outcomes of a pilot study on trans-scleral iontophoresis delivery of lutein in patients with AMD. Topical delivery of lutein directly to the macula may provide a more efficient method for enriching the macular pigment and for achieving greater patient compliance to therapy than oral administration and thus enhancing prevention strategies. Modern diagnostic methodologies shall address the major problem of accurately detecting the risk of transition from intermediate AMD to advanced AMD stages. Adaptive optics retinal imaging and resonance Raman spectroscopy are two highly promising technologies for the objective assessment of patients with AMD. In this review, we present some of their clinical applications for collecting quantitative measurements of retinal cellular changes and macular content of xanthophyll pigments, respectively. In conclusion, there is great expectation that technological advancements in AMD management will deliver improved screening, therapeutic prevention, and diagnostic systems in the coming decade through a pro-active strategy of "treatment for prevention" that will aim to reduce the global burden of vision loss caused by AMD in the elderly.