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 corneal cross-linking (CXL) efficacy in flattening the maximum keratometry (Kmax) index. DESIGN: Prospective, randomized, multicenter, masked clinical trial (ClinicalTrails.gov identifier, NCT05457647). PARTICIPANTS: Fifty patients with progressive keratoconus. INTERVENTION: Participants were stratified to undergo epithelium-off (25 eyes) and epithelium-on (25 eyes) CXL protocols using an ultraviolet A (UV-A) medical device with theranostic software. The device controlled UV-A light both for performing CXL and assessing the corneal riboflavin concentration (riboflavin score) and treatment effect (theranostic score). A 0.22% riboflavin formulation was applied onto the cornea for 15 minutes and 20 minutes in epithelium-off and epithelium-on protocols, respectively. All eyes underwent 9 minutes of 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 classify eyes correctly and predict a Kmax flattening at 1 year after CXL. Other outcome measures included change in Kmax, endothelial cell density, uncorrected and corrected distance visual acuity, manifest spherical equivalent refraction and central corneal thickness 1 year after CXL. RESULTS: Accuracy and precision of the theranostic imaging biomarkers in predicting eyes that had >0.1 diopter (D) of 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 to -0.49 D; P < 0.001); both the uncorrected and corrected distance visual acuity improved by a median of -0.1 logarithm of the minimum angle of resolution (logMAR; IQR, -0.3 to 0.0 logMAR [P < 0.001] and -0.2 to 0.0 logMAR [P < 0.001], respectively). No significant changes in endothelial cell density (P = 0.33) or central corneal thickness (P = 0.07) were noted 1 year after surgery. CONCLUSIONS: The study demonstrated the efficacy of integrating theranostics in a UV-A medical device for the precise and predictive treatment of keratoconus with epithelium-off and epithelium-on CXL protocols. Concentration of riboflavin and its UV-A light mediated photoactivation in the cornea are the primary factors determining CXL efficacy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

Melatonin Enhances Neural Differentiation of Adipose-Derived Mesenchymal Stem Cells.

Adipose-derived mesenchymal stem cells (ASCs) are adult multipotent stem cells, able to differentiate toward neural elements other than cells of mesodermal lineage. The aim of this research was to test ASC neural differentiation using melatonin combined with conditioned media (CM) from glial cells. Isolated from the lipoaspirate of healthy donors, ASCs were expanded in a basal growth medium before undergoing neural differentiation procedures. For this purpose, CM obtained from olfactory ensheathing cells and from Schwann cells were used. In some samples, 1 µM of melatonin was added. After 1 and 7 days of culture, cells were studied using immunocytochemistry and flow cytometry to evaluate neural marker expression (Nestin, MAP2, Synapsin I, GFAP) under different conditions. The results confirmed that a successful neural differentiation was achieved by glial CM, whereas the addition of melatonin alone did not induce appreciable changes. When melatonin was combined with CM, ASC neural differentiation was enhanced, as demonstrated by a further improvement of neuronal marker expression, whereas glial differentiation was attenuated. A dynamic modulation was also observed, testing the expression of melatonin receptors. In conclusion, our data suggest that melatonin's neurogenic differentiation ability can be usefully exploited to obtain neuronal-like differentiated ASCs for potential therapeutic strategies.

Prophylactic Venous Supercharging in Deep Inferior Epigastric Artery Perforator Flap Surgery: A Retrospective Dual-Center Study.

BACKGROUND: Deep inferior epigastric artery perforator (DIEP) flap is nowadays considered the gold standard in breast reconstruction. However, venous congestion is still a leading cause of free flap failure. Despite the conspicuous articles regarding the use of a secondary venous anastomosis, there is a lack in the literature regarding the prophylactic use of a secondary venous route to reduce the incidence of complications during breast reconstruction. METHODS: A double-center retrospective study based on women undergoing DIEP breast reconstruction was conducted, dividing patients into case group (DIEP flaps with double venous anastomosis) and control group (DIEP flaps with single venous anastomosis). Demographic and surgical data and complications were compared and statistically analyzed, and a reconstructive algorithm was proposed to improve the flap insetting. RESULTS: In total, 154 patients were included in the study, divided into case group (74 patients) and control group (80 patients). The median age at the time of surgery was 49.09 years (range: 29-68 years), slightly lower in group 1 when compared with group 2. The mean body mass index (BMI) was 25.52 kg/m2 (range: 21.09-29.37 kg/m2), in particular 25.47 kg/m2 (range: 23.44-28.63 kg/m2) in group 1 and 25.58 kg/m2 (range: 21.09-29.37 kg/m2) in group 2. No statistical differences were found between groups in terms of BMI and smoking and comorbidities history. The average operative times were 272.16 minutes (range: 221-328 minutes) in group 1 and 272.34 minutes (range: 221-327 minutes) in group 2, with no significant difference between groups, as well as ischemia time (44.4 minutes in group 1 [range: 38-56 minutes] and 49.12 minutes in group 2 [range: 41-67 minutes]). Statistical analysis showed a reduction in short-term complications and a statistically significant reduction for take-backs in the two groups. CONCLUSIONS: Our study suggests that venous supercharging of DIEP flap by performing dual venous anastomosis can be routinely and safely done prophylactically, and thus not only after intraoperative assessment of venous congestion, to avoid flap venous congestion and decrease the rates of re-exploration.

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.

Riboflavin/UV-A corneal phototherapy as stand-alone management of ulcerative keratitis in dogs.

Corneal ulcers are one of the most common ocular disorders in veterinary ophthalmology and several factors can negatively influence the efficacy of the currently available therapeutic options, leading to a loss of corneal transparency and, thus, vision. Twenty-five dogs with clinical signs of corneal ulcers were randomised to receive either corneal phototherapy (16 dogs; study group) or topical standard medical therapy (9 dogs; control group). The riboflavin/UV-A corneal phototherapy (PACK-CXL) consisted in the application of a riboflavin ophthalmic solution (Visioflavin®; Vision Engineering Italy srl, Rome, Italy) onto the cornea for 20 min followed by 30 mW/cm2 UV-A irradiance for 3 min using a point-of-care UV-A device (Vetuvir®; Vision Engineering Italy srl, Rome, Italy). The complete healing of the ulcerative lesion was defined as the complete restoration of the corneal epithelial integrity with negative fluorescein staining. The corneal phototherapy achieved complete corneal healing in all the dogs by 20.5 ± 7.8 days. In the control group, only two dogs achieved complete healing by 21.5 ± 15.6 days. This intervention may represent a valid option to hasten corneal wound healing and a clinical resolution of ulcerative keratitis in dogs.

Adverse events after riboflavin/UV-A corneal cross-linking: a literature review.

BACKGROUND: Riboflavin/UV-A corneal cross-linking (CXL) for treating keratoconus and iatrogenic corneal ectasia has been well-established as first treatment option to stabilize corneal tissue biomechanical instability. Although the plethora of clinical studies has been published into the field, there is no systematic review assessing the type and frequency of adverse events after CXL. METHODS: A systemic literature review on clinical safety and adverse events after CXL in patients with keratoconus and corneal ectasia was performed using PubMed. A literature search was performed for relevant peer-reviewed publications. The main outcome measures extracted from the articles were adverse events, endothelial cell density, corrected distance visual acuity and maximum simulated keratometry. RESULTS: The most frequent adverse events after CXL were corneal haze and corneal edema, which were mild and transient. The severe adverse events were infrequent (cumulative incidence: < 1.3%) after CXL. The clinical benefits of CXL highly outweighed the risks for the treatment of keratoconus and corneal ectasia. CONCLUSIONS: The severe adverse events with permanent sequelae are infrequent after CXL and all are associated with corneal de-epithelialization, such as infectious keratitis and corneal scarring.

Ablation of Acid Ceramidase Impairs Autophagy and Mitochondria Activity in Melanoma Cells.

Cutaneous melanoma is often resistant to therapy due to its high plasticity, as well as its ability to metabolise chemotherapeutic drugs. Sphingolipid signalling plays a pivotal role in its progression and metastasis. One of the ways melanoma alters sphingolipid rheostat is via over-expression of lysosomal acid ceramidase (AC), which catalyses the hydrolysis of pro-apoptotic long-chain ceramides into sphingosine and fatty acid. In this report, we examine the role of acid ceramidase in maintaining cellular homeostasis through the regulation of autophagy and mitochondrial activity in melanoma cell lines. We show that under baseline conditions, wild-type melanoma cells had 3-fold higher levels of the autophagy marker, microtubule-associated proteins 1A/1B light chain 3B (LC3 II), compared to AC-null cells. This difference was further magnified after cell starvation. Moreover, we noticed autophagy impairment in A375 AC-null cells, possibly due to local accumulation of non-metabolized ceramides. Nonetheless, we observed that AC-null cells exhibited a significant increase in mitochondrial membrane potential compared to control cells. Consistent with this observation, we found that, after total starvation, ~30% of AC-null cells undergo apoptosis compared to ~6% of wild-type cells. As expected, AC transfection restored viability in A375 AC-null cells. Together, these findings suggest that AC-null melanoma cells change and adapt their metabolism to survive in the absence of AC, although in a way that does not allow them to cope with the stress of nutrient deprivation.

Comparison between standard and transepithelial corneal crosslinking using a theranostic UV-A device.

PURPOSE: To assess corneal concentration of riboflavin in two different corneal crosslinking protocols performed by a novel image-guided therapeutic (or "theranostic") UV-A device. METHODS: Ten human eye bank donor tissues were used in this work. The tissues underwent corneal cross-linking according to the conventional treatment protocol (n = 5; 30 min of stromal soaking followed by 30 min of 3 mW/cm2 UV-A irradiance) and the iontophoresis-assisted transepithelial protocol (n = 5; soaking for 5 min at 1 mA/min and 9 min of 10 mW/cm2 UV-A irradiance) using a theranostic UV-A device (Vision Engineering Italy srl, Italy). The device provided real time assessment of riboflavin concentration by hyperspectral image analysis of the cornea. A 0.1% riboflavin hypotonic solution (Ricrolin+, Sooft Italia Spa, Italy) was used in all cases. RESULTS: Manual application of hypotonic riboflavin for 30 min into the stroma achieved greater corneal riboflavin concentration (425 ± 77 µg/cm3) than transepithelial delivery of riboflavin by corneal iontophoresis (195 ± 35 µg/cm3; P = 0.001). In both UV-A irradiation protocols, corneal riboflavin concentration decreased exponentially with a constant energy rate of 2.3 ± 0.5 J/cm2 and 1.8 ± 0.3 J/cm2 respectively. At the end of treatment, the average corneal concentration of riboflavin decreased by ≥ 85%, with values of 54 ± 29 µg/cm3 and 31 ± 9 µg/cm3 (P = 0.11), respectively. CONCLUSION: Manual application of riboflavin onto the stroma achieved almost 50% greater concentration of riboflavin than transepithelial delivery by corneal iontophoresis. The theranostic UV-A device provided a novel approach to estimate corneal concentration of riboflavin non-invasively during treatment.

Experimental Evaluation of the Thermal Polarization in Direct Contact Membrane Distillation Using Electrospun Nanofiber Membranes Doped With Molecular Probes.

Membrane distillation (MD) has recently gained considerable attention as a valid process for the production of fresh-water due to its ability to exploit low grade waste heat for operation and to ensure a nearly feed concentration-independent production of high-purity distillate. Limitations have been related to polarization phenomena negatively affecting the thermal efficiency of the process and, as a consequence, its productivity. Several theoretical models have been developed to predict the impact of the operating conditions of the process on the thermal polarization, but there is a lack of experimental validation. In this study, electrospun nanofiber membranes (ENMs) made of Poly(vinylidene fluoride) (PVDF) and doped with (1, 10-phenanthroline) ruthenium (II) Ru(phen)3 were tested at different operating conditions (i.e., temperature and velocity of the feed) in direct contact membrane distillation (DCMD). The temperature sensitive luminophore, Ru(phen)3, allowed the on-line and non-invasive mapping of the temperature at the membrane surface during the process and the experimental evaluation of the effect of the temperature and velocity of the feed on the thermal polarization.

Randomized Controlled Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis with the Dresden Protocol in Progressive Keratoconus.

PURPOSE: To compare clinical outcomes of transepithelial corneal cross-linking using iontophoresis (T-ionto CL) and standard corneal cross-linking (standard CL) for the treatment of progressive keratoconus 12 months after the operation. DESIGN: Prospective randomized controlled clinical trial. PARTICIPANTS: Thirty-four eyes of 25 participants with progressive keratoconus were randomized into T-ionto CL (22 eyes) or standard CL (12 eyes). METHODS: T-ionto CL was performed using an iontophoresis device with dextran-free 0.1% riboflavin-5-phosphate solution with enhancers and by irradiating the cornea with a 10 mW/cm2 ultraviolet A device for 9 minutes. Standard CL was performed according to the Dresden protocol. MAIN OUTCOME MEASURES: The primary outcome measure was stabilization of keratoconus after 12 months through analysis of maximum simulated keratometry readings (Kmax, diopters). Other outcome measures were corrected distance visual acuity (CDVA, logarithm of the minimum angle of resolution [logMAR]), manifest spherical equivalent refraction (D), central corneal thickness (CCT, micrometers) and endothelial cell density (ECD). Follow-up examinations were arranged at 3 and 7 days and 1, 3, 6, and 12 months. RESULTS: Twelve months after T-ionto CL and standard CL, Kmax on average flattened by -0.52±1.30 D (P = 0.06) and -0.82±1.20 D (P = 0.04), respectively. The mean change in CDVA was -0.10±0.12 logMAR (P = 0.003) and -0.03±0.06 logMAR (P = 0.10) after T-ionto CL and standard CL, respectively. The manifest spherical equivalent refraction changed on average by +0.71±1.44 D (P = 0.03) and +0.21±0.76 D (P = 0.38), respectively. The CCT and ECD measures did not change significantly in any group at 12 months. Significant differences in the outcome measures between treatments were found in the first week postoperatively. No complications occurred in the T-ionto CL group; 1 eye (8%) had sterile corneal infiltrates, which did not affect the final visual acuity, in the standard CL group. CONCLUSIONS: Significant visual and refractive improvements were found 12 months after T-ionto CL, though the average improvement in corneal topography readings was slightly lower than the Dresden protocol in the same period.

Two-photon optical microscopy imaging of endothelial keratoplasty grafts.

PURPOSE: To investigate the microstructure of endothelial keratoplasty grafts using two-photon optical microscopy. METHODS: Six endothelial keratoplasty grafts obtained from human donor corneoscleral tissues and prepared by submerged hydrodissection technique were imaged by two-photon optical microscopy. In each graft, two liquid bubbles were created in order to investigate the presence of a conserved cleavage plane regardless of the volume of posterior stroma that remained attached to Descemet's membrane (DM); the first bubble (bubble A) was generated under DM and the second bubble (bubble B) injection was done in order to obtain a layer of deep stroma that kept the two bubbles separated. Six human donor corneoscleral tissues were used as controls. Second harmonic generation and two-photon emitted fluorescence signals were collected from each specimen. RESULTS: Dissection of stroma occurred along the posterior collagen lamellae at variable distance from DM, which ranged between 3 and 16 µm in bubble A and between 23 and 41 µm in bubble B. The residual stroma included, anteriorly, bands of collagen lamellae, and thin bundles of stromal collagen fibrils, posteriorly, which were tightly intertwining with the underlying DM. There was no anatomically distinct plane of separation between these pre-Descemetic stromal collagen bundles and the overlying collagen lamellae with this hydrodissection technique. CONCLUSIONS: Two-photon optical microscopy provided label-free high-resolution imaging of endothelial keratoplasty grafts, showing that the most posterior stroma changes organization at approximately 10 µm above the DM. The pre-Descemetic stromal collagen fibrils form an intertwined complex with DM, which cannot be separated using hydrodissection.

Methods for investigating the local spatial anisotropy and the preferred orientation of cones in adaptive optics retinal images.

The ability to noninvasively image the cone photoreceptor mosaic holds significant potential as a diagnostic for retinal disease. Central to the realization of this potential is the development of sensitive metrics for characterizing the organization of the mosaic. Here we evaluated previously-described and newly-developed (Fourier- and Radon-based) methods of measuring cone orientation in simulated and real images of the parafoveal cone mosaic. The proposed algorithms correlated well across both simulated and real mosaics, suggesting that each algorithm provides an accurate description of photoreceptor orientation. Despite high agreement between algorithms, each performed differently in response to image intensity variation and cone coordinate jitter. The integration property of the Fourier transform allowed the Fourier-based method to be resistant to cone coordinate jitter and perform the most robustly of all three algorithms. Conversely, when there is good image quality but unreliable cone identification, the Radon algorithm performed best. Finally, in cases where the cone coordinate reliability was excellent, the method previously described by Pum and colleagues performed best. These descriptors are complementary to conventional descriptive metrics of the cone mosaic, such as cell density and spacing, and have the potential to aid in the detection of photoreceptor pathology.

HIGH-RESOLUTION MULTIMODAL IMAGING AFTER IDIOPATHIC EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To investigate the changes of the vitreomacular interface during a 1-year follow-up after idiopathic epiretinal membrane (iERM) surgery. METHODS: Six patients affected by fovea-attached iERM were recruited in this pilot study. Pars plana vitrectomy associated with epiretinal membrane peeling was performed uneventfully in all cases. In four cases, the inner limiting membrane was removed using Brilliant blue G. En face high-resolution adaptive optics and cross-sectional spectral domain optical coherence tomography retinal imaging were performed before and at 1, 3, 6, and 12 months after surgery. The microstructures of vitreomacular interface in high-resolution adaptive optics images were correlated to the cross-sectional spectral domain optical coherence tomography data. RESULTS: Preoperatively, adaptive optics images showed multiple abnormalities of the vitreomacular interface, such as macrofolds, microfolds, and hyperreflective microstructures. We identified two subtypes of iERM according to the distribution of microfolds over the foveal area, which included the radial-type and the grid-type iERM. After surgery, the morphology of the vitreomacular interface changed compared with the preoperative state. The number of both macrofolds and microfolds was reduced in all cases. The hyperreflective structures were still resolvable in all cases, however presenting different shape and morphology than preoperatively. In addition, they showed marked differences between eyes that had internal limiting membrane removal and eyes that did not. CONCLUSION: Adaptive optics imaging gives new insight into the changes of vitreomacular interface after iERM surgery. Enhanced multimodal imaging of the vitreomacular interface and retinal structures can be valuable to monitor treatment outcome of iERM.

Comprehensive analysis of PTEN status in Sezary syndrome.

Sézary syndrome (SS) is an incurable leukemic variant of cutaneous T-cell lymphoma characterized by recurrent chromosomal alterations, among which, chromosome 10q deletion is very frequent. In this study, we investigated the PTEN status, on locus 10q23, in 44 SS patients; our findings show that PTEN is deleted in 36% of SS cases, whereas PTEN downregulation is observed in almost all of the samples evaluated by quantitative reverse-transcriptase polymerase chain reaction and Western blotting analysis. Neither DNA sequence mutation nor promoter hypermethylation were found at the PTEN locus, but we demonstrate that PTEN level can be also reduced by a group of miRs previously found upregulated and of prognostic relevance in SS; particularly, miR-21, miR-106b, and miR-486 were able to control PTEN abundance either in vitro or in vivo. Finally, because reduced PTEN activates the PI3/AKT-mediated pathway of cell growth and survival, we demonstrate that PTEN deficiency is associated with activated AKT in skin resident but not circulating SS cells, suggesting that the cutaneous milieu may strongly contribute to the SS cell growth. To our knowledge, this is the first study fully exploring the PTEN status in a large cohort of SS patients, unveiling potential elements of clinical utility in this malignancy.

Reconstruction of a Nose Bitten and Eaten by a Dog: A Ten-Year Follow-up of a Bitten-Off Nose Replantation Performed on an Eleven-Year-Old Boy.

The nose is one of the most important aesthetic units of the face. After a traumatic amputation, replantation is undoubtedly the procedure of choice, although, technically, very challenging. We report the 10-year follow-up of a partially digested nose replantation after a dog-bite in an 11-year-old boy using supermicrosurgery technique. Our report confirms that the microsurgical replantation of the nose can lead to an acceptable aesthetic result, with the sufficient growth of the replanted part in the following years. Besides the patient did not report sensibility disorders. The nose replantation in our opinion is the best reconstructive option to achieve an optimal aesthetic and functional outcome.

Adaptive optics imaging of parafoveal cones in type 1 diabetes.

PURPOSE: To evaluate the parafoveal cone density in patients with Type 1 diabetes mellitus (DM1). METHODS: Adaptive optics retinal images of the photoreceptor mosaic were acquired from 11 DM1 patients (study group) and 11 age-matched healthy subjects (control group). Cone density was analyzed, along the horizontal and vertical meridian, at 230-µm, 350-µm, and 460-µm eccentricity from the fovea. Central retinal thickness was measured using a Spectralis spectral-domain optical coherence tomography. A multiple regression model was performed to determine the relationships between the explanatory variables (age, glycohemoglobin level, presence of diabetic retinopathy, duration of diabetes, and central retinal thickness) and cone density. RESULTS: Patients had a diagnosis of DM1 in the past 9 years to 21 years. Of these, five patients had a diagnosis of no diabetic retinopathy and six had mild nonproliferative diabetic retinopathy. On average, cone density was 10% lower in the study than in the control group at each retinal eccentricity along the horizontal and vertical meridians (analysis of variance, P < 0.001). The central retinal thickness was thicker in DM1 eyes than in the control eyes (278 ± 20 µm and 260 ± 13 µm; P < 0.05). The model explained 61% (P < 0.01) of the variance of cone density in the population, with the variables representing an abnormal glucose metabolism, that is, a higher glycohemoglobin level, the presence of diabetic retinopathy, and a chronic diabetes, having the highest influence on cone density decline. CONCLUSION: A subtle decrease of parafoveal cone density was found in DM1 patients in comparison with age-matched control subjects via high-resolution adaptive optics retinal imaging. The cone density decline was moderately associated with a disturbance in the glucose metabolism.

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.

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.