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Introduction: Despite an improved understanding of its pathogenesis, dry eye disease (DED) remains relatively underestimated and its treatment challenging. A better alignment between the clinical evaluation and the patient self-assessment also requires capturing the whole patient experience of DED. This project aimed to unveil this experience through narrative medicine (NM)., Methods: The project involved 38 expert centres in Italy and one in San Marino, targeting adult patients with DED, their informal caregivers and their treating ophthalmologists. Written narratives and sociodemographic and quality of life (QoL)-related data were anonymously collected through the project's webpage. Narratives were analysed through MAXQDA (VERBI Software, Berlin, Germany), NM classifications and content analysis., Results: A total of 171 patients with DED, 37 informal caregivers and 81 ophthalmologists participated in the research. DED was defined as a disabling condition by 19% of patients and 35% of caregivers; 70% of patients reported that a therapeutic alliance is an integral part of DED treatment and 32% hope for more effective therapies. Forty-four per cent of patients assessed their own QoL as good; however, DED emerged as importantly impacting work performance and social events. DED physical, emotional and economic burden and the cruciality of a trusting care relationship represent the main themes that emerged across all narratives, while empathy and effective treatment are among the factors favouring coping with DED., Conclusion: This project marked a pioneering initiative investigating the lived experience of patients with DED through NM, simultaneously involving all viewpoints involved in the care pathway. NM enabled the unveiling of factors favouring the ability to cope with DED and its associated QoL implications and provided valuable insights to improve the therapeutic alliance., (© 2024. The Author(s).)

Introduction: Photobiomodulation (PBM) has become a promising approach for slowing the progression of early and intermediate dry age-related macular degeneration (dAMD) to advanced AMD. This technique uses light to penetrate tissues and activate molecules that influence biochemical reactions and cellular metabolism. This preliminary analysis is aimed at assessing the safety, tolerability, and short-term effectiveness of the EYE-LIGHT ® PBM treatment device in patients with dAMD., Methods: The EYE-LIGHT ® device employs two wavelengths, 590 nm (yellow) and 630 nm (red), in both continuous and pulsed modes. Patients over 50 years of age with a diagnosis of dAMD in any AREDS (Age-Related Eye Disease Study) category were randomly assigned to either the treatment group or the sham group. The treatment plan consisted of an initial cycle of two sessions per week for 4 weeks. Safety, tolerability, and compliance outcomes, along with functional and anatomical outcomes, were assessed at the end of the fourth month., Results: This preliminary analysis included data from 76 patients (152 eyes). All patients were fully compliant with treatment sessions, and only one fifth of patients treated with PBM reported mild ocular adverse events, highlighting exceptional results in terms of tolerability and adherence. Changes in best-corrected visual acuity (BCVA) from baseline to month 4 differed significantly between the sham and PBM-treated groups, favoring the latter, with a higher proportion achieving a gain of five or more letters post-treatment (8.9% vs. 20.3%, respectively; p = 0.043). No significant differences in central subfield thickness (CST) were observed between the two groups over the 4-month period. The study also found a statistically significant disparity in mean drusen volume changes from baseline to month 4 between the groups in favor of patients treated with PBM (p = 0.013)., Conclusion: These preliminary results indicate that PBM treatment using the EYE-LIGHT ® system is safe and well tolerated among patients with dAMD. Furthermore, both functional and anatomical data support the treatment's short-term efficacy., Trial Registration: ClinicalTrials.gov identifier NCT06046118., (© 2024. The Author(s).)

Despite recent advances, pharmacological treatments of diabetic retinopathy (DR) do not directly address the underlying oxidative stress. This study evaluates the efficacy of a nutraceutical formulation based on maltodextrinated grape pomace extract (MaGPE), an oxidative stress inhibitor, in managing DR. A 6-month, randomized, placebo-controlled clinical trial involving 99 patients with mild to moderate non-proliferative DR was conducted. The MaGPE group showed improvement in best-corrected visual acuity (BCVA) values at T3 ( p < 0.001) and T6 ( p < 0.01), a reduction in CRT (at T3 and T6, both p < 0.0001) and a stabilization of vascular perfusion percentage, with slight increases at T3 and T6 (+3.0% and +2.7% at T3 and T6, respectively, compared to baseline). Additionally, the levels of reactive oxygen metabolite derivatives (dROMs) decreased from 1100.6 ± 430.1 UCARR at T0 to 974.8 ± 390.2 UCARR at T3 and further to 930.6 ± 310.3 UCARR at T6 ( p < 0.05 vs. T0). Similarly, oxidized low-density lipoprotein (oxLDL) levels decreased from 953.9 ± 212.4 µEq/L at T0 to 867.0 ± 209.5 µEq/L at T3 and markedly to 735.0 ± 213.7 µEq/L at T6 ( p < 0.0001 vs. T0). These findings suggest that MaGPE supplementation effectively reduces retinal swelling and oxidative stress, contributing to improved visual outcomes in DR patients.

Purpose: To assess the feasibility and the diagnostic accuracy of the new tool, DEvice© (AI, Rome, Italy), for screening patients with dry eye disease (DED)., Methods: This study was performed at the University Magna Græcia of Catanzaro. Enrolled patients were classified as affected by DED (group 1) or not (group 2) using an already validated tool (Keratograph 5M, Oculus, Germany), evaluating the noninvasive keratograph breakup time (NIKBUT), tear meniscus height (TMH), meibomian gland loss (MGL), and bulbar redness. All the patients were then examined by means of DEvice©, which allowed the measurement of the relative humidity (RH) and temperature of the ocular surface. Symptoms were scored using the Ocular Surface Disease Index (OSDI) questionnaire., Results: Overall, 40 patients (17 males and 23 females, mean age 38.0 ± 17.1 years) were included: of these, 20 belonged to group 1 and the remaining 20 to group 2. Using Keratograph 5M, significant differences between groups 1 and 2 were detected for NIKBUT-first (respectively, 4.97 ± 1.85 vs. 13.95 ± 4.8 s; p < 0.0001) and for NIKBUT-average (10.55 ± 4.39 vs. 15.96 ± 4.08 s; p = 0.0003). No statistically significant changes were detected for TMH ( p = 0.565), MGL ( p = 0.051), and bulbar redness ( p = 0.687). Using Device©, a statistically significant higher value of RH was found in group 1 compared to group 2 (respectively, 85.93 ± 10.63 vs. 73.05 ± 12.84%; p = 0.0049). A statistically significant correlation was found between RH and OSDI (r = 0.406; p = 0.009). The value RH showed a discriminating power to detect DED with an AUC = 0.782 (standard error 0.07264; 95% CI 0.6401-0.9249; p = 0.0022)., Conclusions: The DEvice© can effectively discriminate DED patients from healthy subjects. The parameter RH showed good sensitivity, making this tool ideal for a fast and noninvasive DED screening.

Ocular complications can occur in up to 90% of patients with blood malignancies. Such complications range from direct infiltration to local hemostatic imbalance and treatment-related toxicity. This narrative review is based on a systematic computerized search of the literature conducted until January 2024 and examines the common ocular complications associated with blood cancers. Ocular complications from primary disease include mass effects from ocular adnexal lymphomas and intraocular lymphomas, with B-cell lymphomas accounting for 95% of primary ocular presentations. Secondary disease involvement from systemic hematological malignancies can lead to a wide range of ocular manifestations, such as leukemic retinopathy. Furthermore, toxicity from antineoplastic therapies and ocular graft versus host disease (oGVHD) after hematopoietic stem cell transplantation present additional risks to ocular health. In conclusion, ocular complications in blood cancer patients are an integral part of patient management, requiring regular ophthalmic evaluations and close collaboration between oncologists and ophthalmologists. Advances in therapy and an increased focus on early symptom recognition are essential for preserving vision and enhancing patient quality of life.

Purpose: To report the outcomes of a novel microwave heating device (Blepha EyeBag ® ) used serially for the treatment of meibomian gland dysfunction (MGD)., Patients and Methods: This prospective single center study was conducted at University Magna Graecia of Catanzaro. Patients were instructed to apply the compress twice daily for 15 days and once per day every two days, as reported in the package insert. Outcome measures were i) ocular surface disease index (OSDI) score, ii) tear meniscus height (TMH), iii) non-invasive keratograph break-up time (NIKBUT) (first and average), iv) meiboscore, v) bulbar redness. Evaluations were performed at baseline (T0) after 15 days (T1) and after 45 days of therapy (T2)., Results: Overall, 19 patients with MGD (8 males, 11 females; mean age 64.58 ± 9.72 years) were included. The mean value of OSDI score showed a significant decrease from 28.16 ± 17.46 at T0 to 13.69 ± 7.62 at T2 (p=0.008). The mean value of NIKBUT first significantly increased from 6.67 ± 3.51 seconds (s) at T0 to 10.46 ± 4.64 at T2 (p=0.0121); in parallel, the mean value of NIKBUT average increased significantly from 11.09 ± 4.15 s at T0 to 14.95 ± 4.85 at T2 (p=0.0049). No significant differences were detected at each time point for bulbar redness, meiboscore and TMH. Throughout the entire study, no adverse events were recorded., Conclusion: The microwave-heated eye bag treatment is both safe and effective for treatment of MGD, being able to significantly ameliorate both patient-reported symptoms and tear film stability., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Rossi et al.)

(1) Background : Dry eye disease (DED) is a multifactorial ocular surface disease characterized by an imbalance in ocular surface homeostasis, and tear substitutes constitute the first line of treatment. The present study aimed to evaluate the changes in the signs and symptoms of patients with DED treated with a novel tear substitute containing the GlicoPro ® complex. (2) Methods : Patients with DED not successfully responding to other tear substitutes were enrolled and treated with a novel ophthalmic solution (two drops four times daily). Patients were examined before starting the study treatment (T0) and after 30 (T1) and 60 (T2) days of treatment by means of Keratograph for the evaluation of the following: (i) tear meniscus height (TMH); (ii) noninvasive Keratograph break-up time (NIKBUT); (iii) bulbar redness; and (iv) infrared meibography. The SANDE questionnaire was administered to assess ocular discomfort symptoms. Analysis of the tear content of proenkephalin and Met/Leu-enkephalin was also performed. (3) Results : At T2, a significant improvement in NIKBUT first, average, and class, TMH, and SANDE score was found. The tear content of proenkephalins was significantly higher at T1, whereas processed active Met/Leu-enkephalins increased at both T1 and T2. (4) Conclusions : Our novel tear substitute based on GlicoPro ® resulted in a significant improvement in ocular discomfort symptoms, tear volume, and stability in the patients treated. The increase in active peptides processed in tears may represent the pathophysiological substrate underlying this finding., Competing Interests: The authors declare no conflicts of interest.

Purpose: We aimed to evaluate the feasibility of using a novel device, the Smart Eye Camera (SEC), for assessing tear meniscus height (TMH) after fluorescein staining and the agreement of the results with measurements obtained using standard slit lamp examination., Methods: TMH was assessed using both SEC and conventional slit lamp examination. The images were analyzed using the software ImageJ 1.53t (National Institutes of Health, Bethesda, MD, USA). A common measurement unit scale was established based on a paper strip, which was used as a calibration marker to convert pixels into metric scale. A color threshold was applied using uniform parameters for brightness, saturation, and hue. The images were then binarized to black and white to enhance the representation of the tear menisci. A 2 mm area around the upper and lower meniscus in the central eye lid zone was selected and magnified 3200 times to facilitate manual measurement. The values obtained using SEC were compared with those obtained with a slit lamp., Results: The upper and lower TMH values measured using the SEC were not statistically different from those obtained with a slit lamp (0.209 ± 0.073 mm vs. 0.235 ± 0.085, p = 0.073, and 0.297 ± 0.168 vs. 0.260 ± 0.173, p = 0.275, respectively). The results of Bland-Altman analysis demonstrated strong agreement between the two instruments, with a mean bias of -0.016 mm (agreement limits: -0.117 to 0.145 mm) for upper TMH and 0.031 mm (agreement limits: -0.306 to 0.368 mm) for lower TMH., Conclusions: The SEC demonstrated sufficient validity and reliability for assessing TMH in healthy eyes in a clinical setting, demonstrating concordance with the conventional slit lamp examination.

Keratoconus is a corneal disease which results in progressive thinning and protrusion of the cornea leading to irregular astigmatism. The purpose of this study was to evaluate longitudinal changes in corneal volume (CV) occurring over time in keratoconus eyes. Consecutive patients affected by keratoconus were evaluated by means of anterior segment-optical coherence tomography (AS-OCT) at two different time points: baseline (T0) and after 1 year (T1). Anterior and posterior refractive value; corneal thickness at the thinnest point (TP) and corneal volume (CV) calculated within discs of 3, 5 and 8 mm of diameter; anterior chamber depth (ACD); and anterior chamber volume (ACV) were obtained. Enrolled patients were divided into 3 groups (groups 1, 2, 3) according to the increasing disease severity and into 2 groups (groups A, B) according to the progression or stability of the disease. Overall, 116 eyes of 116 patients (76 males and 40 females, mean age 34.76 ± 13.99 years) were included. For the entire group of keratoconus patients, in comparison with T0, mean TP decreased at T1 from 458.7 ± 52.2 µm to 454.6 ± 51.6 µm ( p = 0.0004); in parallel, mean value of CV calculated at 5 mm and 8 mm decreased significantly (from 10.78 ± 0.8 at T0 to 10.75 ± 0.79 at T1 ( p = 0.02), and from 32.03 ± 2.01 mm 3 at T0 to 31.95 ± 1.98 at T1 ( p = 0.02), respectively). Conversely, there were no statistically significant differences in CV at 3 mm from T0 to T1 ( p = 0.08), as well as for ACD and ACV. Regarding the course of the disease, patients belonging to group A showed statistically significant differences from T0 to T1 for TP, and for CV at 3 mm, 5 mm and 8 mm ( p < 0.0001, p < 0.0001, p < 0.001 and p = 0.0058 respectively). There were no statistically significant differences for ACD ( p = 0.6916) and ACV calculated at 3, 5 and 8 mm ( p = 0.7709, p = 0.3765, p = 0.2475, respectively) in group A. At the same time, no statistically significant differences for ACD ( p = 0.2897) and ACV calculated at 3, 5 and 8 mm ( p = 0.9849, p = 0.6420, p = 0.8338, respectively) were found in group B. There were statistically significant positive correlations between changes of TP and CV at 3 mm (r = 0.6324, p < 0.0001), 5 mm (r = 0.7622, p < 0.0001) and 8 mm (r = 0.5987 p < 0.0001). In conclusion, given the strong correlation with TP, CV might be considered an additional AS-OCT parameter to be used in association with conventional parameters when detecting longitudinal changes in keratoconic eyes.

Diabetic macular edema (DME) is a common sight-threatening complication of diabetic retinopathy (DR) and the leading cause of severe visual impairment among the working-age population. Several therapeutic options are available for the management of DME, including intravitreal corticosteroids. They have been traditionally used as second-line treatment, due to the risk of intraocular pressure increase and cataract-related adverse events. However, attention has recently been focused on the primary or early use of intravitreal corticosteroids, due to growing evidence of the crucial role of inflammation in the pathogenesis of DME. Furthermore, intravitreal steroid implants offer the additional advantage of a longer duration of action compared to anti-vascular endothelial growth factor agents (anti-VEGF). This review aims to summarize the available evidence on the efficacy and safety profile of dexamethasone (DEX) intravitreal implant, with a specific focus on clinical scenarios in which it might be considered or even preferred as first-line treatment option by adequate selection of patients, considering both advantages and possible adverse events. Patients with contraindications to anti-VEGF, DME with high inflammatory OCT biomarkers, pseudophakic patients and phakic patients' candidates to cataract surgery as well as vitrectomized eyes may all benefit from first-line DEX implant. Additionally, DME not responders to anti-VEGF should be considered for a switch to DEX implant and a combination therapy of DEX implant and anti-VEGF could be a valid option in severe and persistent DME., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Taloni et al.)

Diabetic retinopathy (DR) is one of the most severe diabetes-related complications, and macular edema stands as the primary contributor to the loss of central vision in individuals diagnosed with diabetes mellitus. The purpose of this study was to investigate the anatomical and functional effects of the oral administration of bromelain and curcugreen in patients controlled by therapy with non-proliferative DR presenting focal edema. Patients were enrolled and divided into two groups: group A (n = 18) received two tablets a day of bromelain and curcugreen (Retinil Forte ® ) orally, and group B (n = 15) underwent observation. The protocol included four visits: the screening visit (T0) and follow-up checks every 3 months up to 12 months (T3-T6-T9-T12). Best-corrected visual acuity (BCVA), central macular thickness (CMT) measured by optical coherence tomography (OCT) and vascular perfusion (VP) in superficial capillary plexus (SCP) and the deep capillary plexus (DCP) measured by optical coherence tomography angiography (OCTA) were analyzed. A mixed-design ANOVA was calculated to determine whether the change in BCVA, CMT, VP in SCP and DCP over time differed according to the consumption of Retinil Forte ® . The results indicated that the interaction between time and treatment on the CMT and VP in DCP were significant, with F (4, 124) = 6.866 ( p < 0.0001) and F (4, 124) = 3.263 ( p = 0.0140), respectively. Conversely, the interaction between time and treatment was not significant on BCVA and VP in SCP with F (4, 124) = 1.121 ( p = 0.3496) and F (4, 124) = 1.473 ( p = 0.2146), respectively. In conclusion, our results suggest a protective role of the oral administration of bromelain and curcugreen in patients with DR and focal edema, in terms of the improvement of baseline CMT and VP in DCP over time.

To compare the performance of humans, GPT-4.0 and GPT-3.5 in answering multiple-choice questions from the American Academy of Ophthalmology (AAO) Basic and Clinical Science Course (BCSC) self-assessment program, available at https://www.aao.org/education/self-assessments . In June 2023, text-based multiple-choice questions were submitted to GPT-4.0 and GPT-3.5. The AAO provides the percentage of humans who selected the correct answer, which was analyzed for comparison. All questions were classified by 10 subspecialties and 3 practice areas (diagnostics/clinics, medical treatment, surgery). Out of 1023 questions, GPT-4.0 achieved the best score (82.4%), followed by humans (75.7%) and GPT-3.5 (65.9%), with significant difference in accuracy rates (always P < 0.0001). Both GPT-4.0 and GPT-3.5 showed the worst results in surgery-related questions (74.6% and 57.0% respectively). For difficult questions (answered incorrectly by > 50% of humans), both GPT models favorably compared to humans, without reaching significancy. The word count for answers provided by GPT-4.0 was significantly lower than those produced by GPT-3.5 (160 ± 56 and 206 ± 77 respectively, P < 0.0001); however, incorrect responses were longer (P < 0.02). GPT-4.0 represented a substantial improvement over GPT-3.5, achieving better performance than humans in an AAO BCSC self-assessment test. However, ChatGPT is still limited by inconsistency across different practice areas, especially when it comes to surgery., (© 2023. The Author(s).)

The aim of this study is to report the clinical outcomes of oral supplementation with curcumin-phospholipid in addition to hyaluronic acid-based tear substitute for the management of dry eye disease (DED). Patients with a diagnosis of DED confirmed by pathological values of both NIKBUT <10 s. and OSDI Questionnaire score > 12 were included. Patients were randomized to receive 2 different treatments: 0.25% hyaluronic acid-based tear substitute 3 time daily (Group 1) or as above plus curcumin-phosphatidylcholine complex tablets once a day (Group 2). Patients were evaluated at baseline (T0) and after 90 days of treatment (T1) by means of Keratograph for the measurement of NIKBUT, TMH, meibomian gland dropout and bulbar redness. Overall, data from 90 eyes of 45 patients were included. Group 1 consisted of 48 eyes of 24 patients, while group 2 included 42 eyes of 21 patients. When comparing median values of both groups at T0, no statistically significant differences were found for all parameters; instead for T1, statistically significant differences were found for redness and OSDI compared to Group 1. In group 1, a statistically significant reduction after the treatment was detected for Nikbut average and OSDI questionnaire; while in group 2, a statistically significant reduction after treatment was recorded for Nikbut average, bulbar redness and OSDI questionnaire. The addition of an oral supplement containing curcumin-phospholipid may help in a greater improvement of bulbar redness and subjective ocular symptoms compared to the treatment with tear substitutes alone for the management of DED., 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 © 2023 Borselli, Ferrari, Bianchi, Rossi, Scalzo, Mangialavori, Scorcia and Giannaccare.)

Background: To evaluate the association between COVID-19 vaccination and retinal vein occlusion (RVO)., Methods: This multicentre self-controlled case series included patients with RVO seen in five tertiary referral centres in Italy. All adults who received at least one dose of the BNT162b2, ChAdOx1 nCoV-19, mRNA-1273 or Ad26.COV2.S vaccine and had a first diagnosis of RVO between January 01, 2021, and December 31, 2021 were included. Incidence rate ratios (IRRs) of RVO were estimated using Poisson regression, comparing rates of events in a 28-day period following each dose of vaccination and in the unexposed control periods., Results: 210 patients were included in the study. No increased risk of RVO was observed after the first dose (1-14 days IRR: 0.87, 95% CI: 0.41-1.85; 15-28 days IRR: 1.01, 95% CI: 0.50-2.04; 1-28 days IRR: 0.94, 95% CI: 0.55-1.58) and second dose of vaccination (1-14 days IRR: 1.21, 95% CI: 0.62-2.37; 15-28 days IRR: 1.08, 95% CI: 0.53-2.20; 1-28 days IRR: 1.16, 95% CI: 0.70-1.90). No association between RVO and vaccination was found in subgroup analyses by type of vaccine, gender and age., Conclusions: This self-controlled case series found no evidence of an association between RVO and COVID-19 vaccination., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

In modern ophthalmology, the advent of artificial intelligence (AI) is gradually showing promising results. The application of complex algorithms to machine and deep learning has the potential to improve the diagnosis of various corneal and ocular surface diseases, customize the treatment, and enhance patient outcomes. Moreover, the use of AI can ameliorate the efficiency of the health-care system by providing more accurate results, reducing the workload of ophthalmologists, allowing the analysis of a big amount of data, and reducing the time and resources required for manual image acquisition and analysis. In this article, we reviewed the most important and recently published applications of AI in the field of cornea and ocular surface diseases, with a particular focus on keratoconus, infectious keratitis, corneal transplants, and the use of in vivo confocal microscopy., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Saudi Journal of Ophthalmology.)

Introduction: The success of keratoplasty strongly depends on the health status of the transplanted endothelial cells. Donor corneal tissues are routinely screened for endothelial damage before shipment; however, surgical teams have currently no means of assessing the overall viability of corneal endothelium immediately prior to transplantation. The aim of this study is to validate a preoperative method of evaluating the endothelial health of donor corneal tissues, to assess the proportion of tissues deemed suitable for transplantation by the surgeons and to prospectively record the clinical outcomes of a cohort of patients undergoing keratoplasty in relation to preoperatively defined endothelial viability., Methods and Analysis: In this multicentre cohort study, consecutive patients undergoing keratoplasty (perforating keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), ultra-thin DSAEK (UT-DSAEK) or Descemet membrane endothelial keratoplasty) will be enrolled and followed-up for 1 year. Before transplantation, the endothelial viability of the donor corneal tissue will be evaluated preoperatively through trypan blue staining and custom image analysis to estimate the overall percentage of trypan blue-positive areas (TBPAs), a proxy of endothelial damage. Functional and structural outcomes at the end of the follow-up will be correlated with preoperatively assessed TBPA values., Ethics and Dissemination: The protocol will be reviewed by the ethical committees of participating centres, with the sponsor centre issuing the final definitive approval. The results will be disseminated on ClinicalTrials.gov, at national and international conferences, by partner patient groups and in open access, peer-reviewed journals., Trial Registration Number: NCT05847387., Competing Interests: Competing interests: YZ, SK and VR are editors of BMJ Open Ophthalmology., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The ocular surface is a complex structure that includes cornea, conjunctiva, limbus, and tear film, and is critical for maintaining visual function. When the ocular-surface integrity is altered by a disease, conventional therapies usually rely on topical drops or tissue replacement with more invasive procedures, such as corneal transplants. However, in the last years, regeneration therapies have emerged as a promising approach to repair the damaged ocular surface by stimulating cell proliferation and restoring the eye homeostasis and function. This article reviews the different strategies employed in ocular-surface regeneration, including cell-based therapies, growth-factor-based therapies, and tissue-engineering approaches. Dry eye and neurotrophic keratopathy diseases can be treated with nerve-growth factors to stimulate the limbal stem-cell proliferation and the corneal nerve regeneration, whereas conjunctival autograft or amniotic membrane are used in subjects with corneal limbus dysfunction, such as limbal stem-cell deficiency or pterygium. Further, new therapies are available for patients with corneal endothelium diseases to promote the expansion and migration of cells without the need of corneal keratoplasty. Finally, gene therapy is a promising new frontier of regeneration medicine that can modify the gene expression and, potentially, restore the corneal transparency by reducing fibrosis and neovascularization, as well as by stimulating stem-cell proliferation and tissue regeneration.

Introduction: The purpose of this short article is to report the clinical outcomes of topical 0.1% ciclosporin cationic emulsion (CsA-CE) used on label in children with vernal keratoconjunctivitis (VKC)., Methods: In this prospective, non-comparative, observational study children affected by active severe VKC were treated for at least 12 months with topical 0.1% CsA-CE. The drug was instilled in both eyes 4 times daily. Data collected from medical charts for the baseline visit (T0) and 1-year follow-up visit (T1) included symptomatic score (0-15), clinical score (0-15), side effects, rescue therapy (need and total number of courses with 0.1% dexamethasone 4 times daily for 5 days), ocular complications and tolerability (visual analog scale [0-100])., Results: Data from 25 children (20 boys, 5 girls; mean [± standard deviation] age 8.40 ± 2.54 years) were included in the study. Of the 25 patients, 23 (92%) used 0.1% CsA-CE eye drops as per label recommendations, including four patients who had prematurely stopped using topical galenic CsA due to side effects. Symptomatic and clinical scores decreased significantly after treatment, with the mean symptomatic score decreasing from 9.76 ± 1.27 at T0 to 3.80 ± 1.08 at T1, and the mean clinical score decreasing from 9.20 ± 1.32 at T0 to 3.44 ± 1.00 at T1; both P < 0.0001). Five patients (20%) required at least one course of rescue medication (mean 3.4 ± 4.8 courses/year). No patients experienced ocular complications during the study, and treatment tolerability was very high (mean score 89.40 ± 5.46)., Conclusion: Our findings confirm that topical CsA-CE is an effective on-label option for children with VKC in the real-life setting. In our pediatric patient population, CsA-CE provided good clinical outcomes with a limited need for rescue medication, and it was well tolerated by almost all patients, including those who were intolerant to galenic formulations., (© 2023. The Author(s).)

Optical coherence tomography angiography (OCTA) is an innovative and reliable technique detecting the early preclinical retinal vascular change in patients with diabetes. We have designed our study to evaluate whether an independent relationship exists between continuous glucose monitoring (CGM)-derived glucose metrics and OCTA parameters in young adult patients with type 1 diabetes without diabetic retinopathy (DR). Inclusion criteria were age ≥ 18 years, diagnosis of type 1 diabetes from ≥ 1 year, stable insulin treatment in the last three months, use of real-time CGM, and CGM wear time ≥ 70%. Each patient underwent dilated slit lamp fundus biomicroscopy to exclude the presence of DR. A skilled operator performed OCTA scans in the morning to avoid possible diurnal variation. CGM-derived glucose metrics from the last 2 weeks were collected through the dedicated software during OCTA. Forty-nine patients with type 1 diabetes (age 29 [18; 39] years, HbA1c 7.7 ± 1.0%) and 34 control subjects participated in the study. Vessel density (VD) of the whole image and parafoveal retina in the superficial (SCP) and deep capillary plexus (DCP) was significantly lower in patients with type 1 diabetes compared to controls. The coefficient of variation of average daily glucose, evaluated by CGM, significantly correlated with foveal and parafoveal VD in SCP and with foveal VD in DCP. High glucose variability might be responsible for the early increase of VD in these areas. Prospective studies may help understand if this pattern precedes DR. The difference we detected between patients with and without diabetes confirms that OCTA is a reliable tool for detecting early retinal abnormalities., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Antonio Cutruzzolà et al.)

Introduction: Postoperative endophthalmitis is typically caused by the patient's conjunctival bacterial flora. Povidone iodine solution (5%) is used perioperatively to obtain periocular and ocular antisepsis. However, an adjunctive prophylaxis procedure could further help control the conjunctival microbial load. Considering the increase in antibiotic resistance, a progressive shift toward alternative methods would be desirable. Somilux ® eye drops (Alfa Intes, lactoferrin-based eye drops) are medical devices containing liposomal lactoferrin (LF). This study evaluates the effects on conjunctival microflora of LF-based eye drops used in the preoperative phase in patients scheduled for cataract surgery., Methods: LF-based eye drops or a vehicle solution (water solution) were instilled 4 times a day starting 3 days before cataract surgery. Before the therapy (T0) and at the time of surgery (T1), a conjunctival swab was performed in both eyes and processed to detect microbial growth, microbiological isolation, and species identification. The outcome was the quantification and characterization of the local microbial flora before and after using LF-based or vehicle-based eye drops. Safety of the treatments was also evaluated., Results: 88 eyes of 44 patients (mean [± SD] age 75 [± 12.6] years) were enrolled. At baseline, 54 conjunctival swabs showed only saprophytic flora, 27 showed only potential pathogenic flora, and seven showed both of them. LF-based eye drops reduced the proportion of potentially pathogenic bacteria (36% at T0 vs. 9% at T1, p = 0.008) compared with the vehicle (41% at T0 vs. 55% at T1, p = 0.302) without altering the physiological ocular microbial composition. No adverse events have been reported., Conclusion: Our findings provide a novel contribution to the scientific knowledge on the role of LF in the ophthalmic field, supporting the use of LF-based eye drops as a safe and selective treatment to improve the ocular surface physiological defenses and control the bacterial ocular surface contamination prior to cataract surgery., (© 2023. The Author(s).)

In this review we discuss the role of intraocular surgery preoperative prophylaxis. The correct choice of antimicrobial drug is variable in each surgical setting, according to the available strengths of evidence, the anatomical district involved, and the type of procedure. In the ophthalmic surgical field, there has been a progressive shift from antibiotic formulations, which are known to cause antibiotic resistance, to a new class of antiseptic compounds, which proved to be effective not only against bacteria, but also against fungi, protozoa, and viruses. Among these, povidone-iodine (PVI) is a water-soluble polymer that can form a complex with iodine, and the perioperative application of PVI 5-10% eye drop for 3 min is the gold standard for infection prophylaxis. A new formulation of 0.6% PVI eye drop is a new option for infection prophylaxis in the days before surgery. Chlorhexidine is a biguanide compound, which is a valid alternative with a good safety and efficacy profile and is the antiseptic of choice in patients with iodine allergy. New compounds that are currently being studied include polyhexamethylene biguanide (PHMB), picloxydine, ozone, hypochlorous acid (HOCl), and Biosecur. PHMB is a biguanide polymer that was found to be more effective than PVI in in vitro studies for reducing microorganisms and extending the duration of antisepsis, but to date, there are no formulations available on the market for preoperative ocular surgery in which it is present as main ingredient. Ozone is a molecule with oxidizing effect, which showed interesting preliminary results but is not effective against virus, Staphylococcus aureus and Candida albicans. HOCl has a natural bactericidal propriety but its applicability to prophylaxis of ocular infection in the setting of ocular surgery is not established. Biosecur is a non-toxic organic alcohol-free compound that exhibited bactericidal and fungicidal effect versus all common microorganisms and is currently available as an ocular spray., (© 2023. The Author(s).)

Descemet membrane endothelial keratoplasty (DMEK) is a popular procedure for the treatment of corneal endothelial diseases mainly targeting Fuchs endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK). Although DMEK has multiple advantages, it is challenging in terms of graft preparation and delivery. One of the crucial factors of DMEK graft preparation is determining the size of the graft. Evaluating risks and benefits of transplanting larger or smaller grafts compared with the descemetorhexis performed following a standard DMEK procedure thus becomes important. Advanced techniques like pre-loaded DMEK requires pre-selection of graft diameter without physical examination of the eye making it more challenging. Therefore, recognizing the benefits of graft size and the number of transplanted endothelial cells becomes essential. Smaller DMEK grafts have been preferred and accepted for grafting. Larger diameter grafts have advantages but can be challenging due to higher detachment rates. We thus aim to review the challenges of preparing and delivering DMEK tissues with small or large diameter based on selected descemetorhexis area, discuss the outcomes based on different graft sizes, highlight related complications and suggest which cases may benefit from adopting smaller or larger graft size., (© 2022 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Introduction: To analyze outcomes on objective ocular surface parameters and subjective symptoms of serial weekly sessions using the Activa mask in patients with meibomian gland dysfunction (MGD)., Methods: This is a prospective study including patients with symptomatic MGD who were treated with four weekly sessions using the Activa mask (SBM Sistemi, Turin, Italy). Noninvasive ocular surface examination was carried out before (T0) and 2 weeks after the last mask session (T1) using Idra (SBM Sistemi, Turin, Italy) for the measurement of: (1) noninvasive break-up time (NIBUT); (2) lipid layer thickness (LLT); (3) tear meniscus height (TMH); (4) meibomian gland loss (MGL) of upper and lower eyelids. The I-Pen tear osmolarity system (I-Med Pharma Inc, Dollard-des Ormeaux, Quebec, Canada) was used to measure tear osmolarity values. Ocular discomfort symptoms were ascertained by means of the ocular surface disease index (OSDI) questionnaire., Results: All 25 patients (11 males, 14 females; mean age 57.1 ± 11.9 years) regularly completed the cycle of four mask sessions. No patients used prohibited medications, and no device-related adverse events were noted. At T1, mean values of NIBUT and LLT increased significantly compared to T0 (respectively from 6.0 ± 1.4 to 6.6 ± 1.2 s, P = 0.043, and from 53.2 ± 17.4 to 65.3 ± 16.3 nm, P < 0.001), while mean values of MGL and tear osmolarity decreased significantly (respectively from 17.1 ± 9.3 to 15.1 ± 8.0%, P = 0.014, and from 307.3 ± 12.2 to 301.5 ± 6.8 mOsm/l, P = 0.005). In parallel, OSDI score reduced significantly from 62.4 ± 11.7 at T0 to 34.5 ± 11.2 at T1 (P < 0.001)., Conclusion: Weekly serial sessions using the Activa mask significantly improved objective parameters of the ocular surface as well as subjective ocular discomfort symptoms in patients with recalcitrant MGD. As a further benefit from the treatment, patients were able to avoid the use of concomitant medications, apart from tear substitutes, throughout the study., (© 2022. The Author(s).)

The COVID-19 pandemic has hampered the optimum management of retinal diseases. This study examined the impact of the pandemic on the intravitreal-injection practice in two academic centers in Italy along with the related medico-legal implications. A retrospective analysis of electronic medical records from 16 March 2020 to 14 March 2021 at the ophthalmological departments of University of Cagliari (SGD) and University Magna Græcia of Catanzaro (UMG) was conducted. The data collected between 16 March 2020 and 14 June 2020 (lockdown), 15 June 2020 and 13 September 2020 (unlock), and 14 September 2020 and 14 March 2021 (second wave) were compared with those of the same period of the previous year. Weekly data on the administered drug and the number and type of treated disease were collected and analyzed. During the lockdown, a drop of 59% at SGD ( p < 0.00001) and 77% at UMG ( p < 0.00001) in intravitreal injections was found. In the first year of the pandemic, the reduction in injections was approximately of 27% ( p < 0.0008) and 38% ( p < 0.0001) at SGD and UMG, respectively. The COVID-19-related containment measures and the health resources redistribution have led to a delay in the treatment of chronic diseases of the retina, prioritizing the undeferrable ones. The lack of management guidelines has conceived relevant ethical and medico-legal issues that need to be considered in future measures planning.

Diabetic retinopathy (DR) often causes a wide range of lesions in the peripheral retina, which can be undetected when using a traditional fundus camera. Widefield (WF) and Ultra-Widefield (UWF) technologies aim to significantly expand the photographable retinal field. We conducted a geometrical analysis to assess the field of view (FOV) of WF and UWF imaging, comparing it to the angular extension of the retina. For this task, we shot WF images using the Zeiss Clarus 500 fundus camera (Carl Zeiss Meditec, Jena, Germany). Approximating the ocular bulb to an ideal sphere, the angular extension of the theoretically photographable retinal surface was 242 degrees. Performing one shot, centered on the macula, it was possible to photograph a retinal surface of ~570 mm 2 , with a FOV of 133 degrees. Performing four shots with automatic montage, we obtained a retinal surface area of ~1100 mm 2 and an FOV of 200 degrees. Finally, performing six shots with semi-automatic montage, we obtained a retinal surface area of ~1400 mm 2 and an FOV of 236.27 degrees, which is close to the entire surface of the retina. WF and UWF imaging allow the detailed visualization of the peripheral retina, with significant impact on the diagnosis and management of DR.

Eye health is crucial, and the onset of diseases can reduce vision and affect the quality of life of patients. The main causes of progressive and irreversible vision loss include various pathologies, such as cataracts, ocular atrophy, corneal opacity, age-related macular degeneration, uncorrected refractive error, posterior capsular opacification, uveitis, glaucoma, diabetic retinopathy, retinal detachment, undetermined disease and other disorders involving oxidative stress and inflammation. The eyes are constantly exposed to the external environment and, for this reason, must be protected from damage from the outside. Many drugs, including cortisonics and antinflammatory drugs have widely been used to counteract eye disorders. However, recent advances have been obtained via supplementation with natural antioxidants and nutraceuticals for patients. In particular, evidence has accumulated that polyphenols (mostly deriving from Citrus Bergamia) represent a reliable source of antioxidants able to counteract oxidative stress accompanying early stages of eye diseases. Luteolin in particular has been found to protect photoreceptors, thereby improving vision in many disease states. Moreover, a consistent anti-inflammatory response was found to occur when curcumin is used alone or in combination with other nutraceuticals. Additionally, Coenzyme Q10 has been demonstrated to produce a consistent effect in reducing ocular pressure, thereby leading to protection in patients undergoing glaucoma. Finally, both grape seed extract, rich in anthocyanosides, and polynsatured fatty acids seem to contribute to the prevention of retinal disorders. Thus, a combination of nutraceuticals and antioxidants may represent the right solution for a multi-action activity in eye protection, in association with current drug therapies, and this will be of potential interest in early stages of eye disorders.

Parkinson disease (PD) is a progressive, neurodegenerative disease of the central nervous system. Visual disturbance is one of the most frequent nonmotor abnormalities referred to by patients suffering from PD at early stages. Furthermore, ocular surface alterations including mainly dry eye and blink reduction represent another common finding in patients with PD. Tears of PD patients show specific alterations related to protein composition, and in vivo confocal microscopy has demonstrated profound changes in different corneal layers in this setting. These changes can be attributed not only to the disease itself, but also to the medications used for its management. In particular, signs of corneal toxicity, both at epithelial and endothelial level, are well described in the literature in PD patients receiving amantadine. Management of PD patients from the ophthalmologist's side requires knowledge of the common, but often underdiagnosed, ocular surface alterations as well as of the signs of drug toxicity. Furthermore, ocular surface biomarkers can be useful for the early diagnosis of PD as well as for monitoring the degree of neural degeneration over time.

Background and Aims: The observation of optical microcirculation gives us an extraordinary way to directly assess in vivo the responses of human circulation to stress stimuli. We run a pilot study to analyze optical coherence tomography angiography (OCT-A) metrics at determined time-points during a hemodialysis (HD) session to understand how these metrics gradually change and to evaluate possible correlations with patients' characteristics., Methods: After the eligibility screening, 15 patients (23 eyes) were included in the study. OCT-A parameters were collected at established time-points: Before treatment (t0), at first hour (t1), at second hour (t2), at third hour (t3), and finally at the end of HD treatment (t4). Patients were finally shared in hypotensive group if they occurred in a hypotensive episode during subsequent month methods or no hypotensive group. The instrument software automatically segmented OCT-A scans into four en-face slabs: The superficial capillary plexus (SCP), the deep capillary plexus (DCP), the outer retinal plexus and the choriocapillaris plexus. In this study we focus on SCP, DCP plexuses., Results: Overall, the majority of ophthalmic parameters remained unaffected and comparable at dialysis end; a significant reduction being observed at the end vs. starting of HD only for deep capillary plexus (DCP: Whole, fovea, and parafovea) and for central choroid thickness (CCT) ( p < 0.05). An overall trend during the session showed in general a decrease with a significance in particular for DCP (whole, fovea, and parafovea) and for CCT ( P = 0.006). In the hypotension group, Superficial capillary plexus (SCP: Fovea and parafovea) significantly increased comparing post vs. pre-dialysis values while CCT significantly decreased. Analyzing the trend during treatment only CCT maintained a significant trend ( p for trend = 0.002). In the no-hypotension group, neither pre- vs. post-analysis and trend analysis showed a statistical significance., Conclusion: Main achievement of our study was to measure, for the first time in literature, single parameters at different time-points of a HD session. As a result of this process we did not notice a brusque decreasing or increasing of OCT-A metrics but we can characterize the different effect of HD on the two distinct areas distinguishing ocular vessels: Retinal and choroidal circulation. As interesting sub-analysis, Hypotensive group showed for CCT a decreasing trend with a difference statistically significant respect to the group with no-hypotension maintaining a constant trend. In our opinion, these results suggest the role of autonomic system on vessel control in patients affected by uremia., 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 Coppolino, Bolignano, Presta, Ferrari, Lionetti, Borselli, Randazzo, Andreucci, Bonelli, Errante, Campo, Mauro, Tripodi, Rejdak, Toro, Scorcia and Carnevali.)

In the current study, using portable optical coherence tomography, we evaluated 46 corneas of 23 individuals in a multicenter setting during the first 17 h after death. Twenty-three eyes were kept open, and twenty three were kept closed. Furthermore, the experiment was carried out for 12 samples in summer and 11 in winter. Our data show that postmortem corneal alterations largely depend on the phenomena of dehydration (in particular in open eyes) and swelling of the stroma in closed eyes, probably due in the first phase to hypoxia/anoxia and subsequently to the passage by osmosis of the aqueous humor from the anterior chamber to the corneal tissue. Our findings could have significant repercussions in forensic pathology for estimating the postmortem interval and transplantation to optimize the conservation of the tissue before the explant.

Introduction: Recently, there has been a progressive shift from simple water-adding medications towards complex multi-action combined formulas aimed at disrupting different mechanisms within the dry eye disease (DED) vicious cycle. This study evaluated the efficacy and tolerability of Trimix eye drops (Off Health Italia, Italy), a combination of viscosity-enhancing hyaluronic acid, trehalose, and cationic liposomes comprising stearylamine and phospholipids, in patients with DED., Methods: In this prospective, pilot study patients diagnosed with mild to moderate DED were enrolled and treated with Trimix eye drops three times daily for 2 months. Ocular surface workup was performed before (V0) and after therapy (V1) by means of IDRA (SBM Sistemi, Turin, Italy), for the measurement of (i) noninvasive break-up time (NIBUT); (ii) tear meniscus height (TMH); (iii) lipid layer thickness (LLT); (iv) infrared meibography (percentage of meibomian gland loss); (v) bulbar redness (Efron scale). Treatment tolerability was scored on a visual analog scale ranging from 0 (none/not at all) to 100 (much/very) for eight questions. Ocular discomfort symptoms were scored using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire., Results: Overall, 25 subjects (mean age 60.32 ± 14.55 years) were included in the study. At V1, TMH, NIBUT, and LLT significantly increased compared to V0 (from 0.29 ± 0.06 to 0.46 ± 0.06 mm, 6.34 ± 2.61 to 7.58 ± 2.52 s, and from 63.26 ± 17.15 to 68.42 ± 15.63 nm, respectively; all P < 0.04). Concerning ocular discomfort symptoms, SPEED score significantly improved at V1 (from 16.63 ± 6.32 to 8.30 ± 5.98; P < 0.001); moreover, treatment tolerability was high for all eight items investigated., Conclusions: Two-month treatment with Trimix formulation improved objective signs and subjective symptoms in patients with DED, showing also a good tolerability profile., (© 2022. The Author(s).)

To investigate whether diurnal changes in noninvasive ocular surface parameters and subjective symptoms occur in healthy subjects wearing face mask who were analyzed before and after 8 h of continuous use. In this prospective cross-sectional study, healthy volunteers attending the same workplace environment underwent a noninvasive ocular surface workup by means of Keratograph 5 M (Oculus, Wetzlar, Germany) in the same day at 2 different time points: (i) in the early morning before wearing face mask (T0); (ii) after 8 h of continuous face mask use (T1). Noninvasive break-up time (NIBUT), tear meniscus height (TMH), ocular redness and meibomian gland dropout were measured. All subjects were asked to complete the Ocular Surface Disease Index (OSDI) questionnaire before and after 8 h of face mask wearing. Data from 20 healthy subjects (10 males and 10 females, mean age 25.1 ± 3.9 years) were included. Mean value of TMH decreased significantly from 0.29 ± 0.07 at T0 to 0.23 ± 0.07 mm at T1 (P < 0.001); conversely, mean values of NIBUT, redness score and meibomian gland dropout did not change significantly after continuous face mask wearing (always P > 0.532). Concerning ocular discomfort symptoms, mean value of OSDI score worsened significantly at T1 compared to T0 (from 12.9 ± 12.6 to 19.4 ± 12.0; P = 0.017). Continuous face mask wearing for 8 h led to decreased TMH associated with the onset of ocular discomfort symptoms in young healthy subjects., (© 2022. The Author(s).)

Background: To evaluate the effects on ocular surface signs and symptoms of serial sessions of heating and vibrating eye mask followed by intense pulsed light (IPL) therapy for the treatment of dry eye disease owing to meibomian gland dysfunction (MGD)., Methods: Consecutive patients with MGD whose signs and symptoms were not satisfactorily controlled with conventional therapy were included. Patients received 3 treatments performed at day 1, 15, and 45 incorporating a session with a newly-developed eye mask (Activa, SBS Sistemi, Turin, Italy) immediately followed by IPL therapy (E > Eye device, E-Swin, Paris, France). Patients were examined before the first session (T0) and 30 days after the last session (T1) for the measurement of: noninvasive break-up time (NIBUT); lipid layer thickness (LLT); tear meniscus height (TMH); meibomian gland loss (MGL); tear osmolarity. Ocular discomfort symptoms were ascertained by ocular surface disease index (OSDI) questionnaire., Results: Thirty patients were ultimately included in the study. At T1, all objective ocular surface parameters improved significantly, except for TMH: NIBUT and LLT increased from 6.4 ± 1.7 to 8.6 ± 1.7 s and from 57.7 ± 15.5 to 81.3 ± 12.0 μm (all P < 0.001), while MGL and tear osmolarity decreased from 21.1 ± 17.3 to 17.0 ± 14.1% and from 302.0 ± 8.5 to 295.7 ± 6.9 mOsm/L (respectively, P = 0.004 and P < 0.001). In parallel, OSDI score decreased significantly from 49.8 ± 13.5 to 29.8 ± 10.6 (P < 0.001). In the historical control group of patients who underwent only IPL, NIBUT, LLT, tear osmolarity and OSDI improved significantly but not MGL and TMH., Conclusions: Serial sessions incorporating the application of an eye mask producing heating and vibration immediately followed by IPL therapy are able to improve all ocular surface parameters as well as ocular discomfort symptoms in MGD patients., (© 2022. The Author(s).)

Introduction: The VISIONARY study examined the intraocular pressure (IOP)-lowering efficacy and tolerability of the preservative-free fixed-dose combination of tafluprost (0.0015%) and timolol (0.5%) (PF tafluprost/timolol FC) in a real-world setting. The country-level data reported herein comprise the largest and first observational study of PF tafluprost/timolol FC therapy in Italy., Methods: An observational, multicenter, prospective study included adult Italian patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) demonstrating insufficient response or poor tolerability with topical prostaglandin analogue (PGA) or beta-blocker monotherapy. Treatment was switched to PF tafluprost/timolol FC therapy at baseline. Primary endpoint was the absolute mean IOP change from baseline at Month 6. Exploratory and safety endpoints included change in IOP at Weeks 4 and 12, ocular signs, symptom severity and reporting of adverse events (AEs)., Results: Overall, 160 OAG/OHT patients were included. Mean ± standard deviation IOP was reduced from 19.6 ± 3.6 mmHg at baseline to 14.5 ± 2.6 mmHg at Month 6 (reduction of 5.1 ± 3.7 mmHg; 24.1%; p < 0.0001). IOP reduction was also statistically significant at Week 4 (23.1%; p < 0.0001) and Week 12 (24.7%; p < 0.0001). Based on data cutoff values for mean IOP change of ≥20%, ≥25%, ≥30% and ≥35%, respective Month 6 responder rates were 68.1%, 48.7%, 36.2% and 26.9%. Most ocular signs and symptoms were significantly reduced in severity from baseline at Month 6. Two non-serious and mild AEs were reported during the study period, among which, one AE was treatment-related (eyelash growth).  ., Conclusion: Italian OAG and OHT patients demonstrated a significant IOP reduction from baseline at Week 4 that was maintained over a 6-month period following a switch from topical PGA or beta-blocker monotherapy to PF tafluprost/timolol FC therapy. Severity of most ocular signs and symptoms was significantly reduced during the study period, and PF tafluprost/timolol FC was generally well tolerated., Competing Interests: Francesco Oddone has received consultancy fees from Santen, Allergan, Sooft, Thea, Omikron Italia, Centervue and Novartis. Vincenzo Scorcia has no relevant financial disclosures. Michele Iester has received consultancy fees from SIFI and Thea, speaker grant from Santen, Omikron Italia and Thea. Dario Sisto has no relevant financial disclosures. Stefano De Cilla has no relevant financial disclosures. Paolo Bettin has not received any fee from any company in the last two years. Carlo Cagini has no relevant financial disclosures. Michele Figus has no relevant financial disclosures. Giorgio Marchini has no relevant financial disclosures. Luca Rossetti received fees from Aerie, Alcon, Allergan, Centervue, Novartis, NTC, Omikron. Gemma Rossi has no relevant financial disclosures. Tommaso Salgarello received no specific funding for this work. Gian Luca Scuderi has received consultancy fees from Santen, Allergan, Sooft, Omikron Italy. Giovanni Staurenghi has received consultant/advisor fees from Heidelberg Engineering, Centervue, Apellis, Allergan, Astellas, Bayer, Boehringer, Genentech, Iveric, Novartis, Roche and Chengdu Kanghong Biotechnology Co, Kyoto Drug Discovery & Development Co; grant support from Heidelberg Engineering, Optos, Optovue, Quantel Medical, Centervue, Carl Zeiss Meditec, Nidek and Topcon; lecture fees from Heidelberg Engineering, Nidek, Bayer, Novartis and Roche; patents/royalty from Ocular Instruments. The authors report no other conflicts of interest in this work., (© 2022 Oddone et al.)

Belantamab mafodotin (belamaf) is a novel antibody-drug conjugate developed for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). Although the drug has demonstrated a good efficacy, corneal adverse events have been reported. In this prospective study, consecutive patients with RRMM who received belamaf infusions were included. The standard ophthalmological visit was implemented with anterior segment (AS)-optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM). Five patients (three males, two females; mean age 66 ± 6.0 years) with MMRR and unremarkable ocular findings at baseline who received belamaf infusion were included. After a median time of 28 days from the first infusion, four of them developed corneal alterations with transient vision reduction to a variable extent. In particular, corneal deposits of microcyst-like epithelial changes (MECs) were detected centrally in one patient and peripherally in three patients. AS-OCT scans showed a bilateral heterogeneous increase in signal intensity, together with hyper-reflective lesions confined within the epithelium in all cases, except for one case in which they also involved the stroma. Corneal maps showed a transient increase in epithelial thickness in the first phase that was followed by a diffuse decrease in the subsequent phase. IVCM scans showed MECs as hyper-reflective opacities located at the level of corneal epithelium, largely intracellular. Multimodal corneal imaging may implement the current clinical scale, helping us to detect corneal abnormalities in patients under belamaf therapy. This workup provides useful data for monitoring over time corneal findings and for optimizing systemic therapy.

Background: The digital revolution is redesigning the healthcare model, and telemedicine offers a good example of the best cost-effectiveness ratio. The COVID-19 pandemic has catalysed the use of the telemedicine. The aim of this review is to describe and discuss the role and the main applications of telemedicine in the ophthalmic clinical practice as well as the related medico-legal aspects., Methods: 45 original articles and 5 reviews focused on this topic and published in English language from 1997 and 2021 were searched on the online databases of Pubmed, Scopus, Web of Sciences and Embase, by using the following key words: "telemedicine", "privacy", "ophthalmology", "COVID-19" and "informed consent"., Results: Telemedicine is able to guarantee patient care using information and communication technologies. Technology creates an opportunity to link doctors with the aim of assessing clinical cases and maintaining high standards of care while performing and saving time as well. Ophthalmology is one of the fields in which telemedicine is most commonly used for patient management., Conclusions: Telemedicine offers benefits to patients in terms of saving time and costs and avoiding physical contact; however, it is necessary to point out significant limitations such as the absence of physical examinations, the possibility of transmission failure and potential violations of privacy and confidentiality.

Purpose: This study evaluates if the addition of a curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier (CHC; Diabec ® , Alfa Intes, Italy) to intravitreal injections of dexamethasone (DEX-IVT) can affect the morphological retinal characteristics, extending the steroid re-treatment period in patients with diabetic macular edema (DME). Methods: A randomized controlled clinical trial was carried out in DME patients, randomly assigned to receive DEX-IVT or DEX-IVT and a CHC. The evaluation of the mean difference of central retinal thickness (CRT) was the primary aim. Secondary aims were the evaluations of best-corrected visual acuity, differences in the predetermined retinal layer thickness, the number/time of re-treatment, and the assessment of safety. Results: A total of 73 DME patients were included (35 in the control group and 38 in the combined therapy group). In both the control and combined therapy groups, the mean CRT change from T 0 to the 6 months' evaluation was significant ( p = 0.00). The mean CRT result was significantly different at month 4 ( p = 0.01) between the control and combined therapy groups, with a greater reduction in the combined therapy group, in particular, in patients with ≤10 years of diabetes. A trend of CRT reduction in the combined therapy group has been observed also considering patients with subfoveal neuroretinal detachment. In addition, we observed that the reduction of inner retinal layer thickness was greater in the combination group, in comparison with controls. Conclusion: The combination of a CHC to DEX-IVT is a promising therapeutic option in case of DME, in particular, for patients with early-stage diabetes and with an inflammatory phenotype. Further studies will be necessary to confirm these findings., 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 Parravano, Allegrini, Carnevali, Costanzo, Giannaccare, Giorno, Scorcia, Spedicato, Varano and Romano.)

Objectives: To analyze the effect of the employment of polyvinylpyrrolidone-iodine (PVP-I) 0.6% eye drop on the clinical course of patients affected by Adenoviral Keratoconjunctivitis (AKC)., Methods: Consecutive patients with clinical signs of AKC and positive results of AdenoPlus test were enrolled from four Italian Centres. Patients were randomized to receive: PVP-I 0.6% eye drops four times/daily for 20 days (Group A) or hyaluronate-based tear substitutes four times/daily for 20 days (Group B). Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) Optovue iVue pachymetry map; corneal haze; conjunctival injection and chemosis; subepithelial corneal infiltrates (SEIs); corneal and conjunctival staining and corneal densitometry were recorded at diagnosis and at every follow-up visit. The primary outcome was the resolution time of AKC., Results: Overall, 59 AKC patients (34 for Group A and 25 for Group B) completed the study. Patients of Group A showed a significantly shorter resolution time and lower incidence of SEIs compared to patients of Group B. In particular, SEIs were present at the last visit in 3/34 (8.82%) patients of the Group A vs 11/25 (44%) of the Group B (p = 0.005). Patients of Group A showed a significantly lower incidence of corneal haze compared to patients of Group B (0/34 vs 3/25; p = 0.038). No side effects were reported for both groups., Conclusions: Although further clinical evaluations are needed, according to our data the use of PVP-I 0.6% eye drop in the setting of AKC reduces the risk of SEIs as well as the resolution time of the disease., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Ocular discomfort and eye pain are frequently reported by patients with dry eye disease (DED), and their management remains a real therapeutic challenge for the Ophthalmologist. In DED patients, injury at the level of each structure of the ocular surface can determine variable symptoms, ranging from mild ocular discomfort up to an intolerable pain evoked by innocuous stimuli. In refractory cases, the persistence of this harmful signal is able to evoke a mechanism of maladaptive plasticity of the nervous system that leads to increased pain responsiveness. Peripheral and, subsequently, central sensitization cause nociceptor hyperexcitability and persistent pain perception that can culminate in the paradoxical situation of perceiving eye pain even in the absence of ocular surface abnormalities. Effective therapeutic strategies of these cases are challenging, and new options are desirable. Recently, a theoretical novel therapeutic approach concerns enkephalins thanks to the evidence that eye pain sensations are modulated by endogenous opioid peptides (enkephalins, endorphins and dynorphins). In this regard, new topical agents open up a new theoretical scenario in the treatment of ocular discomfort and eye pain in the setting of DED, such as, for example, a multimolecular complex based on proteins and glycosaminoglycans also containing opiorphin that may assist the physiological pain-relieving mechanism of the eye.

Objectives: To investigate subclinical and clinical abnormalities in retinal and choroidal vascular plexuses in patients with SSc by means of optical coherence tomography angiography (OCT-A)., Methods: A total of 20 consecutive SSc patients were recruited and compared with 20 healthy subjects. Quantitative analysis of vessel density (VD), choriocapillaris plexus flow index (CCP-FI) and choroidal vascularity index were performed on OCT-A images in the superficial capillary plexus (SCP), deep capillary plexus (DCP) and CCP for all patients. Images were further reviewed by two independent readers for the assessment of qualitative abnormalities, including tortuosity, rarefaction areas, megacapillaries and macular-foveal capillaries., Results: The DCP-VD in the whole scan and in the perifoveal, superior, inferior, nasal and temporal regions was significantly lower in the SSc group. The CCP-FI was significantly higher in SSc patients. When comparing SSc patients with and without digital ulcers, significantly decreased SCP-VD was demonstrated in the whole, perifoveal, superior, inferior, temporal and nasal regions. No difference in any of the OCT-A parameters was observed when comparing patients with and without interstitial lung disease. Qualitative analysis of OCT-A revealed at least one abnormality in 95% of patients., Conclusion: We showed the ability of OCT-A to disclose early ocular vascular abnormalities in patients with SSc. Our results may represent a hypothesis-generating basis for exploring the potential role of OCT-A in diagnosis, monitoring and prognosis stratification in SSc., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: To compare the functional and anatomic outcomes between eyes in patients with diabetic macular edema (DME) who underwent a complete anti-vascular endothelial growth factor (VEGF) loading dose with aflibercept and those who were switched to dexamethasone intravitreal (DEX) implant after an incomplete anti-VEGF treatment regimen during the coronavirus disease 2019 (COVID-19) pandemic., Methods: This was a retrospective and comparative study conducted on patients with DME. Main outcome measures were mean change in best corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 4., Results: Forty-three eyes (23 eyes in the anti-VEGF group and 20 eyes in the DEX group) were included. Mean BCVA significantly improved from 37.7 ± 25.3 and 35.7 ± 22.0 letters at baseline to 45.4 (23.9) (mean adjusted BCVA improvement 7.6 ± 20.8 letters, p = 0.033) and 46.1 ± 26.0 (mean adjusted BCVA improvement 10.6 ± 15.9 letters, p = 0.049) at month 4 in the anti-VEGF and DEX groups, respectively, with no significant differences between study groups (mean adjusted BCVA difference 2.8 letters, 95% CI - 9.4 to 14.9 letters, p = 0.648). There were no statistically significant differences in the proportion of eyes that achieved a BCVA improvement of ≥ 5, ≥ 10, and ≥ 15 letters between groups. CRT was significantly reduced from baseline to month 4 in both DEX (mean adjusted CRT reduction 167.3 ± 148.2 µm, p = 0.012) and anti-VEGF groups (mean adjusted CRT reduction 109.9 ± 181.9 µm, p < 0.001), with no differences between them (mean adjusted CRT difference 56.1 µm, 95% CI - 46.0 to 158.2 µm, p = 0.273). Of 20 eyes in the DEX group, 16 (80.0%) and 9 (45.0%) eyes achieved a CRT reduction of ≥ 20% from baseline at 2 months and at 4 months, respectively., Conclusions: Our results seem to suggest that DEX implant can significantly improve both functional and anatomic clinical outcomes in patients who were unable to complete anti-VEGF loading dose during the COVID-19 pandemic., (© 2021. The Author(s).)

Introduction: The control of conjunctival microbial load is crucial for patients receiving intravitreal injections (IVTs) in order to reduce the risk of endophthalmitis. The purpose of this work was to assess the antimicrobial activity of a new commercial ocular spray containing Biosecur citrus extract (Oftasecur ® , Off Health, Florence, Italy)., Methods: This prospective cross-sectional pilot study included patients receiving IVTs who were instructed to apply Oftasecur spray onto the eye to be injected four times daily starting 4 days before surgery. The contralateral eye was considered the control. A conjunctival swab for microbiological analysis was performed in both eyes before starting study treatment and at the time of the injection. The Brief Ocular Discomfort Inventory (BODI) questionnaire was administered to patients based on an 11-point scale (0 for no discomfort and 10 for maximum discomfort)., Results: Thirty patients (15 male, 15 female; mean age 64.7 ± 11.6 [standard deviation, SD] years) were included. Before starting treatment, 53.3% of the total eyes tested positive during the microbiological analysis. After the treatment period, only 20% of the eyes tested positive at the time of injection, showing a significant reduction in the microbial load (p < 0.01). Moreover, in the treated arm, the positive swabs before and after the prophylactic treatment with Oftasecur ocular spray showed a significant reduction (from 70.4% to 29.6%; p = 0.003, McNemar's test). Oftasecur ocular spray was well tolerated, with an average BODI score of 1.2 (± 0.70 SD)., Conclusion: Oftasecur ocular spray showed antimicrobial activity that significantly reduced the microbial load in patients receiving intravitreal injections. Therefore, it may have a role in the prophylaxis of infection in the setting of IVTs., (© 2021. The Author(s).)