Design of a new 3D printed all-in-one magnetic smartphone adapter for fundus and anterior segment imaging.

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.

RP1 Dominant p.Ser740* Pathogenic Variant in 20 Knowingly Unrelated Families Affected by Rod-Cone Dystrophy: Potential Founder Effect in Western Sicily.

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_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.

COVID-19-related retinal microvasculopathy and systemic implications in patients with severe disease: results from the Methuselah study.

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.

Vision loss due to atypical bilateral edema of the optic nerve in a patient with hereditary angioedema: A case report.

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.

Optic Nerve Head and Retinal Changes in Idiopathic Intracranial Hypertension: Correlation with Short-Term Cerebrospinal Fluid Pressure Monitoring.

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.

Quantitative Diffusion-Weighted MR Imaging: Is There a Prognostic Role in Noninvasively Predicting the Histopathologic Type of Uveal Melanomas?

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 mm2/s in the epithelioid cells, 0.98 ± 0.19 × 10-3 mm2/s in the spindle cells and 0.96 ± 0.26 × 10-3 mm2/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.

Risk factors in the development of retinopathy of prematurity: A 10-year retrospective study.

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.

Anti-vascular endothelial growth factor monotherapy or combined with verteporfin photodynamic therapy for retinal angiomatous proliferation: a systematic review with meta-analysis.

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.

Mid-term safety and effectiveness of macular peeling one month after intravitreal dexamethasone implant for tractional diabetic macular edema.

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 (T0) 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 (T0). 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.

Regulation of UV-B-Induced Inflammatory Mediators by Activity-Dependent Neuroprotective Protein (ADNP)-Derived Peptide (NAP) in Corneal Epithelium.

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-1ß 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.

Qualitative and quantitative analysis of an explanted opacified hydrophilic IOL after over two years from cataract surgery.

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.

Blood-Transfusion Risk Factors after Intramedullary Nailing for Extracapsular Femoral Neck Fracture in Elderly Patients.

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.

Regression of bilateral orbital inflammation with anti-CD20 in a patient with relapsing granulomatosis with polyangiitis: A case report.

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.

Microvascular Changes after Scleral Buckling for Rhegmatogenous Retinal Detachment: An Optical Coherence Tomography Angiography Study.

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.

Heme Oxygenase-1 Overexpression Promotes Uveal Melanoma Progression and Is Associated with Poor Clinical Outcomes.

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.

Polyhexamethylene biguanide hydrochloride (PHMB)-properties and application of an antiseptic agent. A narrative review.

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.

CONVENTIONAL INTERNAL LIMITING MEMBRANE PEELING VERSUS INVERTED FLAP FOR SMALL-TO-MEDIUM IDIOPATHIC MACULAR HOLE: A Randomized Trial.

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.