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Purpose: To compare intravitreal aflibercept alone versus aflibercept combined with oral anti-inflammatory supplementation in patients with diabetic macular edema (DME)., Methods: A prospective, randomized study included 134 treatment-naive eyes with central-involving DME. Participants were assigned to receive either intravitreal aflibercept (Group A) or aflibercept with oral Lenidase® supplementation (Group B, containing baicalin, bromelain, and escin). Both groups followed a treat-and-extend (T&E) regimen. The primary outcome was the number of injections over 24 months. Secondary outcomes included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and safety assessments., Results: At 24 months, Group A required a mean of 14.34 ± 0.51 injections, while Group B required 12.96 ± 0.44 (P < 0.0001). Both groups showed significant improvement in BCVA: from 0.62 ± 0.12 logMAR (20/83 Snellen) to 0.43 ± 0.13 logMAR (20/54 Snellen) in Group A and from 0.64 ± 0.13 logMAR (20/87 Snellen) to 0.42 ± 0.15 logMAR (20/53 Snellen) in Group B (P < 0.0001 for both). CMT also significantly decreased in both groups (P < 0.0001). No significant differences were found between the groups for vision improvement (P=0.918) or CMT reduction (P=0.777). No ocular complications were reported., Conclusions: Oral supplementation with Lenidase® showed similar efficacy to aflibercept monotherapy in DME, with fewer injections, potentially reducing treatment burden.

Purpose: To describe and validate a 3D-printed adapter tool which could be used with either a slit lamp or a condensing lens, interchangeable between devices through magnetic fastening, in order to provide physicians a quick, easy and effective method of obtaining clinical photos., Materials and Methods: Three specialists, with at least 4-year experience in ophthalmology, gave a rate of image quality obtained by our device and the diagnostic confidence grade. The 3 specialists conducted each 13 or 14 examinations with the smartphone and magnetic adapter. At the end of evaluation, they rated with the Likert scale the ease of use of the device in obtaining clinical images of the anterior segment and ocular fundus respectively., Results: Data of quality perception and confidence demonstrated high values not dissimilar to the "de visu" eye examination. Moreover the instrument we designed turned out to be very user friendly., Conclusion: Our adapter coupled with a modern smartphone was able to obtain 4k images and videos of anterior segment, central and peripheral fundus, in an easy and inexpensive way., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background/objectives: Facial pigmented skin lesions are extremely common, starting from the fourth to fifth decades, especially in South-European countries, often located in the periorbital region. These include malignant forms, Lentigo maligna (LM) and lentigo maligna melanoma (LMM), characterized by growing incidence, and a series of benign simulators, including solar lentigo (SL), pigmented actinic keratosis (PAK), seborrheic keratosis (SK) and lichen planus-like keratosis (LPK). The clinical differential diagnosis of atypical pigmented skin lesions (aPFLs) can be difficult, even for dermatologists, leading to inappropriate skin biopsies with consequent aesthetic impacts. Dermoscopy of the facial area is a specific dermoscopic field that requires dedicated training and proved to increase diagnostic accuracy in dermatologists. Since these lesions are often seen by ophthalmologists at first, we aimed to evaluate the effect of a focused dermoscopy training course on a group of ophthalmologists naïve to the use of a dermatoscope., Methods: A set of 80 periorbital pigmented skin lesions with both clinical and dermoscopic images was selected and evaluated by six ophthalmologists before and after a one-day intensive dermoscopic training course. They were required to evaluate 80 periorbital lesions one month before and after a one-day intensive dermoscopic training course, illustrating second-level diagnostic options such as reflectance confocal microscopy (RCM), obtaining a total of 480 evaluations. Specifically, they had to provide, for each case, a punctual diagnosis and a management option among dermoscopic follow-up/skin biopsy/RCM/LC-OCT. Descriptive statistics were carried out, and the accuracy (ACC), sensitivity (SE), and specificity (SP), with their 95% confidence interval (95% CI), were estimated., Results: In the pre-course test, ophthalmologists achieved 84.0% SP, 33.3% SE and 63.7% ACC, while after the course, SE increased by +9% (i.e., 41.7%), SP decreased by 4%, and ACC remained comparable, i.e., 64.6%. In the management study, the percentage of benign lesions for which a close dermoscopic follow-up was suggested significantly decreased (51.6% versus 22.2%), in parallel with an increase in the number of lesions referred for RCM. As for malignant cases, the reduction in responses "close dermoscopic follow-up" decreased from 37.0% to 9.9%, (-27%), in favor of RCM (+15%) and skin biopsy (+12%)., Conclusions: The ophthalmologists proved to be very receptive in quickly metabolizing and putting into practice the concepts learned during the one-day intensive dermoscopy training course. Indeed, after only a one-day lesson, they were able to increase their SE by 9% and to improve their management strategy. The present findings highlight the importance of providing training ophthalmologists in dermoscopy during residency programs, in terms of benefits for the correct patient care., Competing Interests: The authors declare no conflicts of interest.

(1) Background: Ocular emergencies account for 1.5-3% of emergency department (ED) visits and require urgent diagnosis to prevent serious complications. Ultrasonography is a crucial, non-invasive diagnostic tool for these conditions but traditionally lacks portability and integration with modern electronic smart devices. The purpose of this study was to assess the accuracy and performance of a new handheld ultrasound device in comparison to a conventional cart-based sonographic machine in patients attending to the ED for vitreo-retinal diseases. (2) Methods: three specialists in ophthalmology, with at least 4-year experience in vitreo-retinal diseases and eye ultrasound, evaluated images of 50 eyes with both portable and traditional ultrasound probes. Each specialist made the diagnosis based on the images captured with both probes and then rated their overall image quality and confidence of diagnosis with a five-point Likert scale. The concordance of diagnosis between the two probes was evaluated. (3) Results: The sample comprised 42 patients. Twenty (40%) healthy eyes and thirty eyes with the following vitreo-retinal interface conditions were examined: 12 retinal detachment (24%), 8 vitreous hemorrhage (16%), and 10 posterior vitreous detachment (20%). The overall accuracy of the two devices appeared to be comparable (70.7% vs. 69.3%). The Butterfly iQ+ probe showed similar sensitivity in retinal detachment diagnosis (91.7% vs. 94.4% of the Accutome B-scan Pro), while it showed poor performance in diagnosing posterior vitreous detachment (sensitivity = 27.2%); (4) Conclusions: The Butterfly iQ+ device demonstrated high sensitivity in the diagnosis of retinal detachment. Significant adjustments are still needed to improve the resolution of the vitreous body.

Purpose: This retrospective study investigated the impact of corneal parameters on surgically induced astigmatism (SIA) in eyes with prior myopic correction undergoing cataract surgery., Setting: Department of Ophthalmology, San Marino Hospital, San Marino, Republic of San Marino., Design: This case-control study analyzed existing data retrospectively, without randomization or masking., Methods: Eighty eyes divided in group 1 (40 eyes previous underwent refractive surgery for myopia) and group 2 ( 40 myopic eyes) that underwent cataract surgery with intraocular lens (IOL) implantation were included. SIA was calculated using values from the IOL Master Zeiss 700 and mean pupil power (MPP) derived from the CSO Sirius Topographer (based on 3 mm pupil size) with vectorial analysis from doctor Hill software., Results: No significant difference in SIA was observed between eyes with prior myopic photorefractive keratectomy and the control group (p > 0.05). SIA calculations using the IOL Master and CSO Sirius Tomographer yielded similar results. There was no significant correlation between SIA and axial length, corneal curvature, peripheral corneal thickness, or anterior chamber depth (p > 0.05). However, an inverse correlation was found between SIA and horizontal corneal diameter (p < 0.05)., Conclusions: Corneal parameters, such as axial length, corneal curvature, peripheral corneal thickness, and anterior chamber depth, showed no significant influence on SIA. The inverse correlation between SIA and horizontal corneal diameter in study group suggests potential influence of white-to-white distance on SIA. These findings highlight the importance of considering corneal parameters for optimizing surgical outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background/Objectives: Lentigo maligna (LM) and lentigo maligna melanoma (LMM) are significant subtypes of melanoma, with an annual incidence of 1.37 per 100,000 people in the U.S. These skin tumors, often found in photo-exposed areas such as the face, are frequently misdiagnosed, leading to delayed treatment or unnecessary excisions, especially in the elderly. Facial melanocytic skin tumors (lentigo maligna-LM/lentigo maligna melanoma-LMM) and their simulators (solar lentigo, pigmented actinic keratosis, seborrheic keratosis and lichen planus-like keratosis) often affect the periocular region. Thus, their diagnosis and management can involve different medical figures, mainly dermatologists and ophthalmologists. This study aimed to evaluate the ability of ophthalmologists to diagnose and manage pigmented skin lesions of the periorbital area. Methods : A multicentric, retrospective, cross-sectional study on a dataset of 79 periorbital pigmented skin lesions with both clinical and dermoscopic images was selected. The images were reviewed by six ophthalmologists and two dermatologists. Descriptive statistics were carried out, and the accuracy, sensitivity, and specificity, with their 95% confidence interval (95% CI), were estimated. Results: Ophthalmologists achieved a diagnostic accuracy of 63.50% (95% CI: 58.99-67.85%), while dermatologists achieved 66.50% (95% CI: 58.5-73.8). The sensitivity was lower for ophthalmologists in respect to dermatologists, 33.3% vs. 46.9%, respectively. Concerning the case difficulty rating, ophthalmologists rated as "difficult" 84% of cases, while for dermatologists, it was about 30%. Management was also consistently different, with a "biopsy" decision being suggested in 25.5% of malignant lesions by ophthalmologists compared with 50% of dermatologists. Conclusions: Ophthalmologists revealed a good diagnostic potential in the identification of periorbital LMs/LMMs. Given progressive population ageing and the parallel increase in facial/periorbital skin tumors, the opportunity to train new generations of ophthalmologists in the early diagnosis of these neoformations should be considered in the next future, also taking into account the surgical difficulty/complexity of this peculiar facial area.

Primary open angle glaucoma (POAG) is defined as a "genetically complex trait", where modifying factors act on a genetic predisposing background. For the majority of glaucomatous conditions, DNA variants are not sufficient to explain pathogenesis. Some genes are clearly underlying the more "Mendelian" forms, while a growing number of related polymorphisms in other genes have been identified in recent years. Environmental, dietary, or biological factors are known to influence the development of the condition, but interactions between these factors and the genetic background are poorly understood. Several studies conducted in recent years have led to evidence that epigenetics, that is, changes in the pattern of gene expression without any changes in the DNA sequence, appear to be the missing link. Different epigenetic mechanisms have been proven to lead to glaucomatous changes in the eye, principally DNA methylation, post-translational histone modification, and RNA-associated gene regulation by non-coding RNAs. The aim of this work is to define the principal epigenetic actors in glaucoma pathogenesis. The identification of such mechanisms could potentially lead to new perspectives on therapeutic strategies.

Aim: To investigate the efficacy and safety profile of T-shaped pars plana scleral incision technique in removing large intraocular foreign bodies, during 23-gauge pars plana vitrectomy., Methods: Retrospective interventional case series that included patients diagnosed with a large intraocular foreign body (IOFB). Possible postoperative complications were recorded 24 h, 1 month, 3 and 6 months postoperatively., Results: Thirty eyes of 30 patients (48 ± 5 years old) were enrolled. All IOFBs were successfully removed: mean diameters of 7.8 ± 2.0 mm and 2.6 ± 0.3 mm. Silicone oil and sulfur hexafluoride were used in 27 and 3 eyes, respectively. Lensectomy was performed in 27 eyes. Intraocular lens was implanted at first attempt in 12 eyes; during a second operation in 12 eyes and 6 eyes remained aphakic. At any follow-up, no signs of postoperative complications were observed. Secondary retinal detachment occurred in 12 eyes. Mean preoperative corrected distance visual acuity was 0.04, on the Snellen scale; it increased to 0.07, at last follow-up. Mean intraocular pressure was 17.97 mmHg. All eyes were preserved., Conclusion: T-shaped scleral incision could be an effective, safe and easy-to-perform standard procedure to remove large IOFBs during pars plana vitrectomy, without increasing the risk of surgical complications and additional damage to the ocular tissues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Toro, Nowomiejska, Concilio, Motta, Rekas, Costagliola, Avitabile, Castellino, Caputo, Choragiewicz and Rejdak.)

Purpose: To describe a rare case of vision loss due to bilateral edema of the optic nerve in a patient with Hereditary Angioedema, treated with prophylactic C1-esterase inhibitor., Methods: A 60-year-old Caucasian male affected by Hereditary Angioedema with unknown genetic defect (HAE- UNK) was admitted to our hospital presenting bilateral vision loss (best corrected visual acuity of 20/32 in the right eye and hand motion in the left eye) during an HAE attack. Intravenous administration of C1- esterase inhibitor (C1-INH, 1500 IU, Berinert, CSL Behring) determined the resolution of facial and periorbital swelling, however visual impairment persisted, in contrast with previous attacks experienced by the patient. Fundus examination revealed a vital optic disc without papilledema in both eyes. Magnetic resonance imaging (MRI) of the head and orbits showed bilateral edema of the optic nerve sheath. Treatment with intravenous and oral steroids was ineffective. Subsequently, a prophylactic treatment strategy with subcutaneous C1-esterase inhibitor was started (7000 IU every four days)., Results: Complete regression of edema of the optic nerves was observed by imaging at two months of follow-up after chronic treatment with C1-esterase inhibitor (7000 IU every four days). Complete restoration of visual acuity was achieved (BCVA 20/20 in both eyes) and multimodal imaging of the optic nerves demonstrated the absence of anatomical and functional damage., Conclusion: Patients affected by HAE may show atypical presentation with edema of the optic nerves without involvement of the optic nerve head. They may significantly benefit from prophylactic and chronic treatment with C1-esterase inhibitor., Competing Interests: Consent for publicationWritten informed consent was obtained from the patient. Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives . Retinitis pigmentosa (RP) is the most common inherited rod-cone dystrophy (RCD), resulting in nyctalopia, progressive visual field, and visual acuity decay in the late stages. The autosomal dominant form (ADRP) accounts for about 20% of RPs. Among the over 30 genes found to date related to ADRP, RP1 pathogenic variants have been identified in 5-10% of cases. In a cohort of RCD patients from the Palermo province on the island of Sicily, we identified a prevalent nonsense variant in RP1 , which was associated with ADRP. The objective of our study was to analyse the clinical and molecular data of this patient cohort and to evaluate the potential presence of a founder effect. Materials and Methods . From 2005 to January 2023, 84 probands originating from Western Sicily (Italy) with a diagnosis of RCD or RP and their relatives underwent deep phenotyping, which was performed in various Italian clinical institutions. Molecular characterisation of patients and familial segregation of pathogenic variants were carried out in different laboratories using Sanger and/or next-generation sequencing (NGS). Results. Among 84 probands with RCD/RP, we found 28 heterozygotes for the RP1 variant c.2219C>G, p.Ser740* ((NM&#95;006269.2)*, which was therefore significantly prevalent in this patient cohort. After a careful interview process, we ascertained that some of these patients shared the same pedigree. Therefore, we were ultimately able to define 20 independent family groups with no traceable consanguinity. Lastly, analysis of clinical data showed, in our patients, that the p.Ser740* nonsense variant was often associated with a late-onset and relatively mild phenotype. Conclusions . The high prevalence of the p.Ser740* variant in ADRP patients from Western Sicily suggests the presence of a founder effect, which has useful implications for the molecular diagnosis of RCD in patients coming from this Italian region. This variant can be primarily searched for in RP-affected subjects displaying compatible modes of transmission and phenotypes, with an advantage in terms of the required costs and time for analysis. Moreover, given its high prevalence, the RP1 p.Ser740* variant could represent a potential candidate for the development of therapeutic strategies based on gene editing or translational read-through therapy for suppression of nonsense variants.

Objectives: To assess the reversibility of retinal microvascular changes in the long term and to investigate the potential links with other vascular diseases of COVID-19., Methods: We designed a prospective multicenter observational study. Patients were enrolled from the Methuselah study cohort. Retinal vascular function was studied in these patients using optical coherence tomography angiography (OCTA); aortic stiffness was measured using aortic pulse wave velocity. These examinations were performed 1 (Visit 1) and 12 (Visit 2) months after the hospital discharge for severe COVID-19. A control subject group matched for age and sex was included to define normal values., Results: A total of 28 control subjects (56 eyes) and 25 patients (50 eyes) completed the scheduled OCTA assessment; 18 patients (36 eyes) also completed the macrovascular examination. Compared to controls, the vessel density of the superficial capillary plexus (SCP) was reduced, whereas the foveal avascular zone area was enlarged at Visit 1 ( p  = 0.016 and < 0.001, respectively) and was not modified after the 12-month follow-up in COVID-19 patients ( p  = 0.011 and 0.001, respectively). Higher inflammation and lower renal function during hospitalization were linked to higher aortic stiffness and reduced vessel density of the SCP 1 month after the acute phase of COVID-19. A slower recovery of aortic dysfunction was linked to worse retinal vascular outcomes at Visit 2., Conclusion: Retinal vascular alterations were not reversible 12 months after COVID-19 and were linked to inflammation and renal dysfunction during hospitalization as well as to aortic stiffness measured during follow-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Castellino, Longo, Russo, Bonfiglio, Fallico, Toro, Cappellani, Grillo, Gaudio, Lo Cicero, Sessa, Colaci, Malatino, Castellino, Avitabile and Zanoli.)

Background: We aimed to assess the status of the optic nerve and retina by optical coherence tomography (OCT) in a group of patients with idiopathic intracranial hypertension (IIH) on the basis of dynamic changes in intracranial pressure., Methods: This observational and cross-sectional study included patients affected by idiopathic intracranial hypertension with papilledema (IIHWP) and patients with idiopathic intracranial hypertension without papilledema (IIHWOP). All participants underwent an OCT examination of the macula and optic nerve head. Parameters related to intracranial pressure, including cerebrospinal fluid (CSF) opening pressure (oCSFp), CSF mean pressure (mCSFp), and pulse wave amplitude (PWA), were included in the analysis., Results: Out of the 22 subjects enlisted for the study, a total of 16 patients suggestive of IIH were finally enrolled. Papilledema was detected in nine subjects (56.2%) and seven patients were affected by IIHWOP (43.7%). The OCT examination showed a higher mean RNFL thickness in IIHWP patients in comparison to IIHWOP in both eyes ( p < 0.05 and p < 0.01, respectively). Intracranial pressure (ICP) measurements showed that IIHWP had higher values of oCSFp, mCSFp, and PWA compared to IIHWOP ( p = 0.0001, p = 0.0001, and p = 0.0001, respectively). In addition, ICP parameters significantly correlated with RNFL., Conclusions: Clinical parameters suggestive of idiopathic intracranial hypertension are associated with retina and optic nerve OCT parameters. OCT is a useful tool to detect these alterations in a non-invasive fashion.

Histopathologically, uveal melanomas (UMs) can be classified as spindle cell, mixed cell and epithelioid cell type, with the latter having a more severe prognosis. The aim of our study was to assess the correlation between the apparent diffusion coefficient (ADC) and the histologic type of UMs in order to verify the role of diffusion-weighted magnetic resonance imaging (DWI) as a noninvasive prognostic marker. A total of 26 patients with UMs who had undergone MRI and subsequent primary enucleation were retrospectively selected. The ADC of the tumor was compared with the histologic type. The data were compared using both one-way analysis of variance (ANOVA) (assessing the three histologic types separately) and the independent t -test (dichotomizing histologic subtypes as epithelioid versus non-epithelioid). Histologic type was present as follows: the epithelioid cell was n = 4, and the spindle cell was n = 11, the mixed cell type was n = 11. The mean ADC was 1.06 ± 0.24 × 10 -3 mm 2 /s in the epithelioid cells, 0.98 ± 0.19 × 10 -3 mm 2 /s in the spindle cells and 0.96 ± 0.26 × 10 -3 mm 2 /s in the mixed cell type. No significant difference in the mean ADC value of the histopathologic subtypes was found, either when assessing the three histologic types separately ( p = 0.76) or after dichotomizing the histologic subtypes as epithelioid and non-epithelioid ( p = 0.82). DWI-ADC is not accurate enough to distinguish histologic types of UMs.

Opacification of hydrophilic intraocular lenses (IOLs) is an uncommon complication, that can appear after uneventful cataract surgery. We report a case of opacified Hydroview® IOL in a 76-year-old woman, with a previous history of pars plana vitrectomy with silicon oil tamponade in her right eye for a proliferative diabetic retinopathy, who developed an opacification of the IOL after over two years from a silicon oil/BSS exchange in combination with an uneventful phacoemulsification. The patient complained about a progressive decrease in her visual acuity. The slit-lamp examination confirmed the opacification of the IOL. Therefore, because of blurred vision, a combined procedure of explant and exchange of the IOL was performed in the same eye. Qualitative (Optic microscope, X-Ray powder Diffraction (XRD), Scanning Electron Microscopy (SEM)) and quantitative (Instrumental Neutron Activation Analysis (INAA)) analysis of the IOL material were performed. Here, our aim is to report the acquired data of the explanted Hydroview® H60M IOL., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To evaluate Retinopathy of Prematurity (ROP) rate and risk factors in a large cohort of preterm newborns., Methods: Single center retrospective study. All preterm inborn hospitalized at the Neonatal Intensive Care Unit of the Policlinico of Catania from January 1, 2009 till December 31, 2018, were included. ROP stage and location, treatments required, maternal and infant risk factors were evaluated., Results: Medical records of 898 preterms were retrospectively examined (mean gestational age 32.9 ± 2.3 weeks). Of them 149 (16.6 %) developed bilateral ROP (92 stage 1, 44 stage 2 and 13 stage 3); 66 (7.3 %) received bilateral laser treatment. Six eyes of three patients affected by zone I ROP 1, with plus persistence 15 days after an optimal laser treatment, also received intravitreal ranibizumab injection. Risk factors for ROP development were gestational age (GA) (p < 0.001), birthweight (p < 0.001), assisted ventilation duration (p < 0.001), multiple birth (p = 0.003), erythropoietin (EPO) administration (p = 0.005) and persistence of tunica vasculosa lentis. The decision-tree analysis showed gestational age as the most significant predictive factor (P < 0.001); secondary predictive factors were EPO administration (p = 0.001) in newborns 29-31 weeks GA and birthweight lower than 2090 g (p < 0.001) in 32-34 weeks GA; in this latter group patent ductus arteriosus (PDA) was a tertiary predictive factor (p = 0.043)., Conclusions: In our study ROP incidence was 16,6 %; 7.3 % of the patients required laser treatment. Besides well-known factors, such as GA and birthweight, other factors like duration of assisted ventilation, EPO, multiple births, PDA, tunica vasculosa lentis persistence should be considered to tailor ophthalmic evaluation and follow-up., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To describe a case of bilateral orbital inflammation in a patient with relapsing granulomatosis with polyangiitis as only sign of disease recurrency treated with anti-CD20 antibodies., Methods: A 62-year-old Caucasian man affected by Granulomatosis with polyangiitis (GPA) was admitted to our hospital showing bilateral orbital inflammation as the only signs of disease recurrency. In addition, eye visit detected severe visual loss in the left eye (light perception). Guidelines to manage severe orbital involvement in patients with GPA are lacking. The patient was treated with intravenous rituximab and glucocorticoids., Results: Complete regression of inflammatory signs by imaging were observed at three-year of follow-up after the treatment with anti-CD20. However, ocular multimodal imaging showed severe optic nerve damages in the left eye with irreversible visual loss., Conclusion: Patients affected by GPA with inflammatory orbital involvement may benefit from anti-CD20 antibodies.

Purpose: To assess functional and anatomical outcomes of intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) monotherapy versus combined with verteporfin Photodynamic Therapy (PDT) for Retinal Angiomatous Proliferation (RAP). Methods: Studies reporting outcomes of intravitreal anti-VEGF monotherapy and/or in combination with verteporfin PDT in RAP eyes with a follow-up ≥ 12 months were searched. The primary outcome was the mean change in best corrected visual acuity (BCVA) at 12 months. Mean change in central macular thickness (CMT) and mean number of injections were considered as secondary outcomes. The mean difference (MD) between pre- and post-treatment values was calculated along with 95% Confidence Interval (95% CI). Meta-regressions were performed to assess the influence of anti-VEGF number of injections on BCVA and CMT outcomes. Results: Thirty-four studies were included. A mean gain of 5.16 letters (95% CI = 3.30-7.01) and 10.38 letters (95% CI = 8.02-12.75) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.01). A mean CMT reduction of 132.45 µm (95% CI = from -154.99 to -109.90) and 213.93 µm (95% CI = from -280.04 to -147.83) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.02). A mean of 4.9 injections (95% CI = 4.2-5.6) and 2.8 injections (95% CI = 1.3-4.4) were administered over a 12-month period in the anti-VEGF group and combined group, respectively. Meta-regression analyses showed no influence of injection number on visual and CMT outcomes. High heterogeneity was found across studies for both functional and anatomical outcomes. Conclusion: A combined approach with anti-VEGF and PDT could provide better functional and anatomical outcomes in RAP eyes compared with anti-VEGF monotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer GR declared a shared affiliation with the authors MF, AM, GF, MB, RM, AA, AR, AL, TA, and NC to the handling editor at the time of review., (Copyright © 2023 Fallico, Macchi, Maugeri, Favara, Barchitta, Magnano San Lio, Agodi, Russo, Longo, Avitabile, Castellino, Reibaldi, Pignatelli, Vadalà, Patanè, Nebbioso and Bonfiglio.)

Macular peeling combined or followed by intravitreal dexamethasone implant (DEX-i) was recommended as an efficacy approach for tractional diabetic macular edema (tDME). Knowing the synergistic effect of cataract surgery and DEX-i one month earlier in eyes with DME, we compared Epiretinal Membrane/Inner Limiting Membrane (ERM/ILM) peeling preceded by DEX-i one month before versus ERM/ILM peeling alone for the treatment of tDME. A retrospective study on patients affected by tDME who underwent ERM/ILM peeling one month after DEX-i (n = 11; Group A) or ERM/ILM peeling alone (n = 10; Group B) was performed. Longitudinal comparison of best-correct visual acuity (BCVA), central retinal thickness (CRT), and intraocular pressure (IOP) between the time of surgery (T 0 ) and each time point (months 1,3,5,6) within and among the groups were assessed. To evaluate the repeated measurements of BCVA, CRT, and IOP, a linear mixed-effects model was used. In Group A, DEX-i significantly improved mean BCVA and CRT (P < 0.001) just after 1 month (T 0 ). After ERM/ILM peeling, mean BCVA and CRT significantly improved from month 1 in Group A and month 3 in Group B. Mixed model revealed a significant difference in BCVA (P ≤ 0.0001) and CRT (P ≤ 0.02) at different time-points among the groups with better results in Group A. Neither complications nor uncontrolled IOP increase was detected. ERM/ILM peeling confirmed its effectiveness in treating tDME. DEX-i performed one month before surgery seemed to be a safe approach and ensured a greater and faster recovery considering functional and tomographic parameters., (© 2023. The Author(s).)

The corneal epithelium, representing the outermost layer of the cornea, acts as a barrier to protect the eye against external insults such as ultraviolet B (UV-B) radiations. The inflammatory response induced by these adverse events can alter the corneal structure, leading to visual impairment. In a previous study, we demonstrated the positive effects of NAP, the active fragment of activity-dependent protein (ADNP), against oxidative stress induced by UV-B radiations. Here, we investigated its role to counteract the inflammatory event triggered by this insult contributing to the disruption of the corneal epithelial barrier. The results indicated that NAP treatment prevents UV-B-induced inflammatory processes by affecting IL-1β cytokine expression and NF-κB activation, as well as maintaining corneal epithelial barrier integrity. These findings may be useful for the future development of an NAP-based therapy for corneal disease.

Background: Extracapsular femoral neck fractures (eFNF) are the third most common type of fracture in traumatology. Intramedullary nailing (IMN) is one of the most frequently used ortho-pedic treatments for eFNF. Blood loss is one of the main complications of this treatment. This study aimed to identify and evaluate the perioperative risk factors that lead to blood transfusion in frail patients with eFNF who undergo IMN., Methods: From July 2020 to December 2020, 170 eFNF-affected patients who were treated with IMN were enrolled and divided into two groups according to blood transfusion: NBT (71 patients who did not need a blood transfusion), and BT (72 patients who needed blood transfusion). Gender, age, BMI, pre-operative hemoglobin levels, in-ternational normalized ratio (INR) level, number of blood units transfused, length of hospital stay, surgery duration, type of anesthesia, pre-operative ASA score, Charlson Comorbidity Index, and mortality rate were assessed., Results: Cohorts differed only for pre-operatively Hb and surgery time ( p < 0.05)., Conclusion: Patients who have a lower preoperative Hb level and longer surgery time have a high blood-transfusion risk and should be closely followed peri-operatively., Competing Interests: The authors declare no conflict of interest.

This retrospective study aimed to investigate macular microvascular alterations after successful scleral buckling (SB) for rhegmatogenous retinal detachment (RRD). Nineteen eyes with macula-on RRD and 18 eyes with macula-off RRD were included. In all cases, an encircling band was placed. Optical coherence tomography angiography (OCTA) was performed at baseline and postoperatively. Changes in the foveal avascular zone (FAZ) area and vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were the primary outcomes. Correlations between OCTA findings and clinical variables were considered secondary outcomes. In both the macula-on and macula-off groups, the FAZ area was comparable with controls. In the macula-on group, VD in the whole SCP was lower compared with controls at both baseline (p < 0.001) and 6 months (p = 0.03), but showed a significant increase after surgery (p = 0.004). In the macula-off group, postoperative VD in both whole SCP and whole DCP was lower compared with controls (p < 0.001). In the macula-on group, there was an inverse correlation between axial length increase and SCP VD change (r = −0.508; p = 0.03). These findings demonstrated microvascular alterations after SB for RRD. However, VD impairment seems to be mitigated after surgery. A greater increase in postoperative axial length was associated with a poorer VD outcome.

Purpose: To compare conventional internal limiting membrane (ILM) peeling versus inverted flap technique in small-to-medium idiopathic macular hole., Methods: Eyes with ≤400 μ m idiopathic macular holes were randomized into the conventional ILM peeling group (25 eyes) and inverted flap group (25 eyes). A 12-month follow-up was considered. Macular sensitivity (MS) change detected with MP-1 microperimetry was the primary outcome. Secondary outcomes included best-corrected visual acuity change, closure rate, anatomical findings on optical coherence tomography such as U-shape foveal contour, restoration of external limiting membrane, and ellipsoid zone., Results: In both groups, MS improved throughout the follow-up. Final MS was greater in the conventional ILM peeling group compared with the inverted flap group, being 16.6 ± 2.3 dB versus 14.9 ± 2.9 dB, respectively ( P = 0.026). In both groups best-corrected visual acuity improved throughout the follow-up, with a final best-corrected visual acuity of 0.19 ± 0.14 logMar (20/31 Snellen) in the conventional ILM group and 0.22 ± 0.11 logMar (20/33 Snellen) in the inverted flap group ( P = 0.398). Anatomical hole closure was achieved in all cases. No difference in optical coherence tomography findings was shown between the two groups., Conclusion: A better final MS was found in eyes undergoing conventional ILM peeling. Inverted flap technique has disadvantages compared with conventional peeling for the treatment of small-to-medium idiopathic macular holes., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Uveal melanoma (UM) is the most common primary intraocular tumor in adults. To date, the main strategies to counteract its progression consist of focal radiation on the tumor site and ocular enucleation. Furthermore, many UM patients develop liver metastasis within 10 years following diagnosis, eventually resulting in a poorer prognosis for those patients. Dissecting the molecular mechanism involved in UM progression may lead to identify novel prognostic markers with significative clinical applications. The aim of the present study was to evaluate the role of Heme Oxygenase 1 (HO-1) in regulating UM progression. UM cell lines (92.1) were treated with Hemin (CONC e time), a strong inducer of HO-1, and VP13/47, a selective inhibitor of its enzymatic activity. Interestingly, our results showed an enhanced 92.1 cellular proliferation and wound healing ability following an HO-1 increase, overall unveiling the role played by this protein in tumor progression. Similar results were obtained following treatment with two different CO releasing molecules (CORM-3 and CORM-A1). These results were further confirmed in a clinical setting using our UM cohort. Our results demonstrated an increased median HO-1 expression in metastasizing UM when compared to nonmetastasizing patients. Overall, our results showed that HO-1 derived CO plays a major role in UM progression and HO-1 protein expression may serve as a potential prognostic and therapeutical factor in UM patients.

The prevention and management of ocular surface infections is still one of the great challenges for ophthalmologists. The spread of antimicrobial resistance makes it necessary to use antiseptic substances with a broad antimicrobial spectrum. Polyhexamethylene biguanide hydrochloride (Polyhexanide, PHMB) is a broad-spectrum antiseptic with excellent tolerance and a low-risk profile. Its physicochemical action on the phospholipid membrane and DNA replication or repair mechanism, prevents or impedes the development of resistant bacterial strains. PHMB revealed its effective against numerous organisms like viruses, Gram-negative and Gram-positive bacteria, and fungi. Polyhexanide is commonly used as preservative in commercially available disinfecting solutions for contact lens care and in ophthalmic formulations at different concentrations ranging from 1 µg/ml to 50 µg/ml. The administration of 0.02% (200 µg/ml) PHMB is often the first-line therapy of Acanthamoeba keratitis. However, to date, only one close-out randomized controlled study tested the efficacy of 0.02% PHMB in Acanthamoeba keratitis and a phase III study is still ongoing. This paper reviews the antiseptic agent PHMB, focusing on biochemical mechanisms, safety profile and applications in ophthalmology.

Describe drug utilisation and clinical outcomes of intravitreal anti-VEGF drug and dexamethasone use in the real-world setting in Southern Italy using data from multi-centre study of retinal disease. Clinical data of retinal disease patients treated with anti-VEGF drugs and dexamethasone implant in 6 out-patient ophthalmology centres from Southern Italy were collected by means of an electronic case report form. Patients receiving at least one intravitreal injection/implant of the study drugs were followed for up to two years and described in terms of demographics and clinical characteristics. Drug utilisation patterns were described. A sign-rank test was used to compare clinical data on visual acuity and other ophthalmic parameters from baseline at different follow-up times for each indication. Data from 1327 patients was collected. Most patients were diagnosed with age-related macular degeneration (AMD) (660, 49.7%), followed by diabetic macular oedema (423, 31.9%), retinal vein occlusion (164, 12.3%), and myopic choroidal neovascularization (80, 6.0%). Patients were followed for a median of 10.3 months (interquartile range: 3.6 - 24.7 months). Mean patient age was 69.7 (±10.9) years and 54.2% were males. Ranibizumab (55.4%) and aflibercept (27.5%) were the most commonly used drugs. Baseline visual acuity significantly improved by about 0.05 to 0.1 logMAR at all follow-up times for AMD and RVO but less consistently for the other diseases. Intravitreal ranibizumab use accounted for half of all treatment for retinal diseases in a Southern Italian out-patient setting. Patients treated with anti-VEGF drugs for AMD and RVO in Southern Italy experienced significant improvement in VA.

Background: The introduction of non-invasive diagnostic tools in ophthalmology has significantly reshaped current clinical practice in different settings. Recently, different anterior segment (AS) intraoperative optical coherence tomography (i-OCT) systems have been employed for different interventional procedures including cataract surgery., Materials and Methods: A review on the use of AS i-OCT in the management of cataract surgery, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The level of evidence according to the Oxford Centre for Evidence-Based Medicine (OCEM) 2011 guidelines, and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were assessed for all included articles., Results: Out of 6302 articles initially extracted, 6302 abstracts were identified for screening and 32 of these met the inclusion/exclusion criteria for full-text review; 19 articles were excluded., Conclusions: The use of AS i-OCT in cataract surgery, even if only a few studies have a high level or grade of evidence, may represent a useful tool for novel surgeons approaching phacoemulsification but also for expert ones for teaching purposes and to plan and manage complicated cases.

Topic: To investigate whether an increasing number of intravitreal anti-VEGF injections is associated with a higher mortality risk., Clinical Relevance: The issue of systemic safety of intravitreal anti-VEGF therapy has been long discussed. Evidence from meta-analyses of randomized studies has shown no increased risk of mortality in the overall population, whereas some warning signals of higher mortality were found in patients with diabetes exposed to intense and prolonged treatment. Concerns have been raised about whether an increasing number of anti-VEGF injections could be associated with a higher mortality., Methods: Randomized clinical trials enrolling arms with different intensities of anti-VEGF therapy were searched. The primary outcome measure was the incidence rate ratio (IRR) of death with 95% confidence interval (CI) for receiving 5 injections. The relationship between the number of injections and all-cause mortality was investigated. Separate regression analyses were conducted to investigate this relationship in subgroups of studies with different diseases and drugs., Results: Fifty-two trials were included. Overall mortality rates of 1.02% and 3.36% were recorded at 12 and 24 months, respectively. Univariate regression showed that a larger number of injections was not associated with a significant increase in mortality both at 12 months (IRR, 1.16; 95% CI, 0.87-1.53; P = 0.31) and at 24 months (IRR, 1.05; 95% CI, 0.95-1.15; P = 0.34). According to subgroup analyses, in diabetic macular edema (DME) studies, a higher risk was marginally associated with an increasing number of injections at 24 months (IRR, 1.17; 95% CI, 1.02-1.33; P = 0.03)., Conclusion: No significant influence of anti-VEGF treatment intensity on mortality was shown, supporting a message of reassurance over safety concerns of this therapy. Marginal evidence of a higher risk associated with a more intense treatment was found in patients with DME., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: To examine the effect of subthreshold micropulse yellow laser (SMYL) on best-corrected visual acuity (BCVA), central macular thickness (CMT), and optical coherence tomography angiography (OCT-A) changes in eyes with persistent diabetic macular edema (DME) after pars plana vitrectomy (PPV) for tractional DME (TDME). Patients and Methods: In a comparative study, 95 eyes of 95 consecutive patients with persistent DME were prospectively enrolled. The SMYL group (54 eyes) was treated with SMYL 6 months after PPV, while the control group (41 eyes) was followed up without treatment. BCVA and CMT by OCT were analyzed at baseline and 3 and 6 months. Additionally, parameters such as the vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), respectively, and the area of the foveal avascular zone (FAZ) were also evaluated on OCT-A. Results: There were no significant differences between both groups in demographic data. In the SMYL group, mean BCVA was significantly increased [F(2,106) = 17.25; p < 0.001; η p 2 = 0.246] from 51.54 ± 13.81 ETDRS letters at baseline to 57.81 ± 12.82 ETDRS letters at 3 months ( p < 0.001) and 57.83 ± 13.95 EDTRS letters at 6 months ( p < 0.001), respectively. In comparison to the control group, BCVA values were statistically significantly higher in the SMYL group at 3 and 6 months, respectively. Mean CMT significantly decreased [F(2,106) = 30.98; p < 0.001; η p 2 = 0.368] from the baseline value 410.59 ± 129.91 μm to 323.50 ± 89.66 μm at 3 months ( p < 0.001) and to 283.39 ± 73.45 μm at 6 months ( p < 0.001). CMT values were significantly lower in the SMYL group ( p < 0.001), especially at 6 months follow-up time ( p < 0.001) compared with the control group. Parafoveal VD in the SCP and DCP was significantly higher in the SMYL group in comparison to the control group, respectively, at 3-month (SCP p < 0.001; DCP p < 0.001) and 6-month follow-up (SCP p < 0.001; DCP p < 0.001). FAZ area was also significantly smaller in the SMYL group at 6-month follow-up ( p = 0.001). There were no adverse SMYL treatment effects. Conclusion: SMYL therapy may be a safe and effective treatment option in eyes with persistent macular edema following PPV for TDME., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bonfiglio, Rejdak, Nowomiejska, Zweifel, Justus Wiest, Romano, Bucolo, Gozzo, Castellino, Patane, Pizzo, Reibaldi, Russo, Longo, Fallico, Macchi, Vadalà, Avitabile, Costagliola, Jonak and Toro.)

Uveal melanoma (UM) is the most common primary intraocular tumor in adults and usually has a very poor prognosis. Histologically, UMs have been classified in epithelioid cell type, spindle cell type, and mixed cell type. Balloon cells are large pale cells that contain small, hyperchromatic, central nuclei with vesiculated, clear, and lipid-rich cytoplasm. A balloon cell morphology is infrequently observed in naevi and even less frequently in malignant melanomas of the skin, conjunctiva, ciliary body and choroid. In this regard, UMs that exhibit balloon cell features are generally those previously treated with proton beam irradiation and then enucleated, rather than those that directly underwent primary surgery. To the best of our knowledge, very few cases of primary UM showing extensive balloon cell morphology have been reported in scientific literature to date. We herein present an unusual case of primary UM with diffuse balloon cell changes in a 69-year-old woman.

Scleral buckling represents a valuable treatment option for rhegmatogenous retinal detachment repair. The surgery is based on two main principles: the closure of retinal breaks and the creation of a long-lasting chorioretinal adhesion. Buckles are placed onto the sclera with the purpose of sealing retinal breaks. Cryopexy is usually performed to ensure a long-lasting chorioretinal adhesion. Clinical outcomes of scleral buckling have been shown to be more favorable in phakic eyes with uncomplicated or medium complexity retinal detachment, yielding better anatomical and functional results compared with vitrectomy. Several complications have been described following scleral buckling surgery, some of which are sight-threatening. Expertise in indirect ophthalmoscopy is required to perform this type of surgery. A great experience is necessary to prevent complications and to deal with them. The use of scleral buckling surgery has declined over the years due to increasing interest in vitrectomy. Lack of confidence in indirect ophthalmoscopy and difficulties in teaching this surgery have contributed to limiting its diffusion among young ophthalmologists. The aim of this review is to provide a comprehensive guide on technical and clinical aspects of scleral buckling, focusing also on complications and their management.

The corneal epithelium, the outermost layer of the cornea, acts as a dynamic barrier preventing access to harmful agents into the intraocular space. It is subjected daily to different insults, and ultraviolet B (UV-B) irradiation represents one of the main causes of injury. In our previous study, we demonstrated the beneficial effects of pituitary adenylate cyclase-activating polypeptide (PACAP) against UV-B radiation damage in the human corneal endothelium. Some of its effects are mediated through the activation of the intracellular factor, known as the activity-dependent protein (ADNP). In the present paper, we have investigated the role of ADNP and the small peptide derived from ADNP, known as NAP, in the corneal epithelium. Here, we have demonstrated, for the first time, ADNP expression in human and rabbit corneal epithelium as well as its protective effect by treating the corneal epithelial cells exposed to UV-B radiations with NAP. Our results showed that NAP treatment prevents ROS formation by reducing UV-B-irradiation-induced apoptotic cell death and JNK signalling pathway activation. Further investigations are needed to deeply investigate the possible therapeutic use of NAP to counteract corneal UV-B damage.

Necrosis in uveal melanomas can be spontaneous or induced by radiotherapy. The purpose of our study was to compare the histopathologic and MRI findings of radiation-induced necrosis of a group of proton beam-irradiated uveal melanomas with those of spontaneous necrosis of a control group of patients undergoing primary enucleation. 11 uveal melanomas who had undergone proton beam radiotherapy, MRI and secondary enucleation, and a control group of 15 untreated uveal melanomas who had undergone MRI and primary enucleation were retrospectively identified. Within the irradiated and nonirradiated group, 7 and 6 eyes with histological evidence of necrosis respectively, were furtherly selected for the final analysis; the appearance of necrosis was assessed at histopathologic examination and MRI. Irradiated melanomas showed a higher degree of necrosis as compared with nonirradiated tumors. Irradiated and nonirradiated lesions differed based on the appearance and distribution of necrosis. Irradiated tumors showed large necrotic foci, sharply demarcated from the viable neoplastic tissue; nonirradiated tumors demonstrated small, distinct foci of necrosis. Radiation-induced necrosis, more pigmented than surrounding viable tumor, displayed high signal intensity on T1-weighted and low signal intensity on T2-weighted images. The hemorrhagic/coagulative necrosis, more prevalent in nonirradiated tumors (4 out of 6 vs. 1 out of 7 cases), appeared hyperintense on T2-weighted and hypointense on T1-weighted images. Our study boosts the capability to recognize radiation-induced alterations in uveal melanomas at MRI and may improve the accuracy of radiologists in the evaluation of follow-up MR examination after radiotherapy.

Background/objectives: To compare the number of eye surgical procedures performed in Italy in the 2 months following the beginning of lockdown (study period) because of COVID-19 epidemic with those performed in the two earlier months of the same year (intra-year control) and in the period of 2019 corresponding to the lockdown (inter-year control)., Methods: Retrospective analysis of surgical procedures carried out at 39 Academic hospitals. A distinction was made between elective and urgent procedures. Intravitreal injections were also considered. Percentages for all surgical procedures and incidence rate ratios (IRR) for rhegmatogenous retinal detachment (RRD) events were calculated. A p value <0.05 was considered significant., Results: A total of 20,886 versus 55,259 and 56,640 patients underwent surgery during the lockdown versus intra-and inter-year control periods, respectively. During the lockdown, only 70% of patients for whom an operation/intravitreal injection was recommended, finally underwent surgery; the remaining patients did not attend because afraid of getting infected at the hospital (23%), taking public transportation (6.5%), or unavailable swabs (0.5%). Elective surgeries were reduced by 96.2% and 96.4%, urgent surgeries by 49.7% and 50.2%, and intravitreal injections by 48.5% and 48.6% in the lockdown period in comparison to intra-year and inter-year control periods, respectively. IRRs for RRDs during lockdown dropped significantly in comparison with intra- and inter-year control periods (CI: 0.65-0.80 and 0.61-0.75, respectively, p  < 0.001 for both)., Conclusion: This study provides a quantitative analysis of the reduction of eye surgical procedures performed in Italy because of the COVID-19 epidemic.

Purpose: To evaluate the safety, effectiveness, and the best parameters setup of hypersonic vitrectomy., Methods: A prospective, multicentric, interventional study on 50 eyes that had undergone hypersonic vitrectomy because of various vitreoretinal diseases. We primarily assessed the effectiveness of vitreous removal, intraoperative complications, and surgical setup. Secondarily, we evaluated single-surgery anatomical success and postoperative best-corrected visual acuity., Results: Intraoperative complications occurred in 5 eyes (10%), whereas technical problems were detected in 23 eyes (46%), resulting in conversion to guillotine vitrectomy in 15 cases. The most common finding related to the technical problems was an inadequate vitreous liquefaction with the formation of vitreous strands and consequent inadequate vitreous outflow, sometimes complicated by vitreous incarceration in the vitrectomy probe. The best settings were considered a stroke of 60 µm and vacuum of 40 mmHg for both core and peripheral vitrectomy. At 3-month follow-up, primary anatomical success was achieved in 49 eyes (98%) and the mean best-corrected visual acuity overall improved., Conclusion: The availability of hypersonic vitrectomy in the current surgical practice opens a new era in vitreoretinal surgery. Despite the potential advantages in fluidics, the performance of hypersonic vitrectomy system needs to be further optimized, mainly for the occurrence of inadequate vitreous liquefaction and vitreous strands formation.