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Aim: Diabetic retinopathy (DR) represents the main cause of vision loss among working age people. A prompt screening of this condition may prevent its worst complications. This study aims to validate the in-built artificial intelligence (AI) algorithm Selena+ of a handheld fundus camera (Optomed Aurora, Optomed, Oulu, Finland) in a first line screening of a real-world clinical setting. Methods: It was an observational cross-sectional study including 256 eyes of 256 consecutive patients. The sample included both diabetic and non-diabetic patients. Each patient received a 50°, macula centered, non-mydriatic fundus photography and, after pupil dilation, a complete fundus examination by an experienced retina specialist. All images were after analyzed by a skilled operator and by the AI algorithm. The results of the three procedures were then compared. Results: The agreement between the operator-based fundus analysis in bio-microscopy and the fundus photographs was of 100%. Among the DR patients the AI algorithm revealed signs of DR in 121 out of 125 subjects (96.8%) and no signs of DR 122 of the 126 non-diabetic patients (96.8%). The sensitivity of the AI algorithm was 96.8% and the specificity 96.8%. The overall concordance coefficient k (95% CI) between AI-based assessment and fundus biomicroscopy was 0.935 (0.891–0.979). Conclusions: The Aurora fundus camera is effective in a first line screening of DR. Its in-built AI software can be considered a reliable tool to automatically identify the presence of signs of DR and therefore employed as a promising resource in large screening campaigns. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the qualitative and quantitative differences between 20 and 85 kHz A-scan rate optical coherence tomography (OCT) images acquired by spectral domain OCT. The study included 60 healthy subjects analyzed with horizontal linear scans with a variable A-scan rate (SHIFT technology, Heidelberg Engineering, Heidelberg, Germany). The retinal thickness measurement of each retinal layer was performed in three different positions (subfoveal, nasal, and temporal). The qualitative assessment was performed by two independent observers who rated every image with a score ranging from 1 ("sufficient") to 3 ("excellent") on the basis of three parameters: visualization of the vitreo-retinal interface, characterization of the retinal layers, and visualization of the sclero-choroidal interface. No statistically significant differences in terms of retinal layer thickness between the two A-scan rate scans were observed (p > 0.05). The coefficient of variation of the retinal thickness values was lower in the 20 kHz group (25.8% versus 30.1% with the 85 kHz). The 20 kHz images showed a higher quality index for both observers. An inner plexiform layer (IPL) multilaminarity was detected in 78.3% of patients from the 20 kHz group and in 40% of patients from the 85 kHz group (p < 0.05). [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) and deep learning (DL)-based systems have gained wide interest in macular disorders, including diabetic macular edema (DME). This paper aims to validate an AI algorithm for identifying and quantifying different major optical coherence tomography (OCT) biomarkers in DME eyes by comparing the algorithm to human expert manual examination. Intraretinal (IRF) and subretinal fluid (SRF) detection and volumes, external limiting-membrane (ELM) and ellipsoid zone (EZ) integrity, and hyperreflective retina foci (HRF) quantification were analyzed. Three-hundred three DME eyes were included. The mean central subfield thickness was 386.5 ± 130.2 µm. IRF was present in all eyes and confirmed by AI software. The agreement (kappa value) (95% confidence interval) for SRF presence and ELM and EZ interruption were 0.831 (0.738–0.924), 0.934 (0.886–0.982), and 0.936 (0.894–0.977), respectively. The accuracy of the automatic quantification of IRF, SRF, ELM, and EZ ranged between 94.7% and 95.7%, while accuracy of quality parameters ranged between 99.0% (OCT layer segmentation) and 100.0% (fovea centering). The Intraclass Correlation Coefficient between clinical and automated HRF count was excellent (0.97). This AI algorithm provides a reliable and reproducible assessment of the most relevant OCT biomarkers in DME. It may allow clinicians to routinely identify and quantify these parameters, offering an objective way of diagnosing and following DME eyes. [ABSTRACT FROM AUTHOR]

Simple Summary: Carbonic anhydrase inhibitors such as dorzolamide, brinzolamide, and acetazolamide are prescription drugs prohibited in sports. Detecting these substances and their biomarkers of consumption in urine and hair is crucial to documenting misuse in doping. We quantified dorzolamide, brinzolamide, acetazolamide, and their metabolites in the urine and hair of 88 patients under treatment, and samples of the patients' relatives were analyzed to assess potential for accidental exposure. We found that cutoff concentrations of urinary dorzolamide and brinzolamide are necessary to preclude false positives due to contamination or passive exposure. Additionally, we reported the first concentrations of brinzolamide in hair. Carbonic anhydrase inhibitors (CAIs) are prescription drugs also used in doping to dilute urine samples and tamper with urinalyses. Dorzolamide, brinzolamide, and acetazolamide are prohibited by the World Anti-Doping Agency. Detecting CAIs and their metabolites in biological samples is crucial to documenting misuse in doping. We quantified dorzolamide, brinzolamide, acetazolamide, and their metabolites in the urine and hair of 88 patients under treatment for ocular hypertension or glaucoma. Samples of the patients' relatives were analyzed to assess potential for accidental exposure. After washing, 25 mg hair was incubated with an acidic buffer at 100 °C for 1 h. After cooling and centrifugation, the supernatant was analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Urine (100 μL) was diluted and centrifuged before UHPLC-MS/MS analysis. Run time was 8 min through a reverse-phase column with a mobile phase gradient. MS/MS analysis was performed in a multiple-reaction monitoring mode after positive electrospray ionization. Median urinary concentration was 245 ng/mL (IQR: 116.2–501 ng/mL) for dorzolamide, 81.1 ng/mL (IQR: 35.9–125.3 ng/mL) for N-deethyl-dorzolamide, 0.77 ng/mL (IQR: 0.64 ng/mL–0.84 ng/mL) for N-acetyl-dorzolamide, 38.9 ng/mL (IQR: 20.4–79.2 ng/mL) for brinzolamide, and 72.8 ng/mL (IQR: 20.7–437.3 ng/mL) for acetazolamide. Median hair concentration was 0.48 ng/mg (IQR: 0.1–0.98 ng/mg) for dorzolamide, 0.07 ng/mg (IQR: 0.06–0.08 ng/mg) for N-deethyl-dorzolamide, 0.40 ng/mL (IQR: 0.13–1.95 ng/mL) for brinzolamide. Acetazolamide was detected in only one hair sample. Dorzolamide and brinzolamide were detected in the urine of three and one relatives, respectively. Cutoff concentrations of urinary dorzolamide and brinzolamide are necessary to preclude false positives due to contamination or passive exposure. We reported the first concentrations of brinzolamide in hair. [ABSTRACT FROM AUTHOR]

Introduction: The 0.19 mg fluocinolone acetonide (FAc) intravitreal implant delivers a continuous intravitreal corticosteroid dose for the treatment of refractory diabetic macular oedema (DMO). The aim of this study was to assess the impact of an FAc intravitreal implant on intraocular pressure (IOP). Methods: We retrospectively collected anonymised data on the patients' characteristics, DMO treatment, and IOP and IOP-lowering treatments before and after the FAc intravitreal implant between September 2013 and March 2020 in several European centres. Results: A total of 221 eyes from 179 patients were included. The mean follow-up duration was 13.4 (± 12.5, range 2.4–33.5) months. Overall, 194 eyes (88.2%) had received an intravitreal dexamethasone injection before the FAc intravitreal implant. For 25 eyes (11.3%) there was a history of glaucoma, and 52 eyes (23.5%) had previous IOP-lowering treatment. Mean IOP before injection was 14.7 (3.4) mmHg and increased to 16.9 (3.7) mmHg 12 months after injection (P < 0.0001). During follow-up, 55 eyes (24.9%) required the addition or initiation of topical IOP-lowering medication, only one patient (0.5%) had laser trabeculoplasty and one patient (0.5%) a minimally invasive glaucoma surgery, and no patient required incisional IOP-lowering surgery. Conclusion: The FAc intravitreal implant led to substantial IOP elevation. This elevation was monitored most of the time with addition or initiation of topical IOP-lowering medication. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the presence of pachychoroid spectrum disease (PSD) in patients with Cushing disease (CD) and to evaluate subfoveal choroidal thickness (SFCT) and choriocapillary flow using spectral domain OCT (SD-OCT) with the enhanced depth imaging (EDI) and optical coherence tomography angiography (OCT-A). Methods: Thirty-two patients with CD and 32 age- and sex-matched healthy volunteers were enrolled in this observational study. All participants had a complete ophthalmic examination including SD-OCT with EDI and OCT-A, and were subjected to the Perceived Stress Scale test (PSS). All patients with CD had hormone test including 24-h urinary-free cortisol (UFC) and plasma adrenocorticotropic hormone (ACTH). We compared SFCT and choriocapillary vessel density (CVD) between the two groups and evaluated the presence of PSD. We investigated the association of hormone level, SFTC, CVD with the presence of CD; the association between the hormone level, SFTC, CVD, the CD disease activity, and duration with the presence of PSD in CD patients; and the association between SFTC and CVD with the hormone level, the CD disease activity, and duration in CD patients. Results: Higher values of SFCT and CVD were associated with CD (β: 0.028, 95% CI: 0.014; 0.041; β: 0.912, 95%CI: 0.205; 1.62, respectively). Twelve patients with CD (37.5%) reported a PSD in at least one eye, whereas no subject was found in control group (p < 0.001); in particular, 11 CD patients (34%) presented pachychoroid pigment epitheliopathy (PPE) and 1 CD patient (3%) presented polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization (PCV/AT1). In patients with CD, a significant positive association between SFCT and PSD was found (β: 0.010, 95% CI 0.001; 0.019). Conclusion: A chronic state of hypercortisolism may have direct implications on the choroid. Patients with CD had higher SFCT values and a significant change in the choriocapillary flow compared to healthy controls. Moreover, PSD was observed only in CD patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the correlations between anatomical and functional changes in idiopathic macular hole (IMH) surgery in long-term follow-up. Methods: This is a prospective, interventional single centre case series. The final sample is formed by 14 eyes of 14 patients who had undergone IMH surgery in our institution between 2005 and 2009 and were still followed up in 2019. Reported data were pre- and post-operative best-corrected visual acuity (BCVA), retinal sensitivity and fixation stability values on MP-1 and structural macular features on spectral domain optical coherence tomography. Optical coherence tomography angiography (OCTA) was utilized to assess microvascular characteristics at the final visit. Only patients with a successful MH closure were enrolled, excluding eyes affected by other relevant pathologies. Results: Mean BCVA improvement was significant after surgery (t test, p value < 0.001) and presented a slight, not statistically significant raise, between the post-operative and long-term follow-up. Differently, mean retinal sensibility (dB) showed a highly statistically significant difference between pre-operative and post-operative (t test, p value =.002) and post-operative and last follow-up (p value < 0.001). In the long-term follow-up, subjects having integrity of the inner segment/outer segment (IS/OS) layer showed no statistically significant difference in BCVA compared with subjects with IS/OS discontinuity (t test, p value = 0.72). OCTA parameters of the operated eye showed no statistical significance compared with the fellow eye. Conclusions: In successfully closed MHs, retinal sensibility measured by microperimetry significatively increases after a long follow-up period even when BCVA remains stable or raises slightly. Vessel density organization tends to be quantitatively similar to fellow eye several years after surgery. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the changes in anterior chamber flare after a single intravitreal injection of ocriplasmin (125 μg), in patients with symptomatic vitreomacular traction syndrome (VMT). Study design: An institutional review board-approved single-center not randomized prospective study. Methods: Fifteen eyes of fifteen patients (9 women, 6 men) underwent intravitreal injection with ocriplasmin for symptomatic VMT (width of attachment ≤ 1500 μm). Anterior segment flare was measured with a laser flare meter (Kowa) before intravitreal injection and 1 day, 1 week, 1 month after injection. The changes in flare were analyzed; the resolution of VMT was evaluated with spectral-domain OCT. Results: The mean anterior chamber flare was 10.5 ± 1.9 photons per millisecond (photons/ms) before the injection. After 1 day it increased to 13.6 ± 2.7 photons/ms (p = 0.027) and after 1 week to 14.4 ± 2.5 photons/ms (p = 0.005); after 1 month it decreased to 12.3 ± 2.3 photons/ms (p = 0.123). At 1 day and 1 week after injection, mean anterior chamber flare of fellow eyes was significantly lower than study eyes, while at 1 month this difference was not significant (12.3 ± 2.3 vs. 10.5 ± 1.8 photons/ms, p = 0.124, for study and fellow eyes). There was no statistically significant difference in the changes in flare between women and men or between phakic (N = 10) and pseudophakic (N = 5) eyes. No eye demonstrated intraretinal damage at any time-point. Also, 9 eyes showed resolution of VMT while 6 eyes demonstrated persistence of VMT. Conclusion: Our study shows that intravitreal injection of ocriplasmin can be a safe and effective approach to treat symptomatic VMT syndrome in selected patients. [ABSTRACT FROM AUTHOR]

Purpose: To describe functional and histopathological findings after macular peeling using different dyes.Methods: Prospective, randomized, comparative, interventional, and immunohistochemical study. Forty-five eyes from 45 patients with idiopathic epiretinal membrane (ERM) underwent pars plana chromovitrectomy with ERM and inner limiting membrane (ILM) using trypan blue 0.15% + brilliant blue 0.05% + lutein 2% in group 1 (15 eyes), trypan blue 0.15% + brilliant blue 0.025% + polyethylene glycol 3350 4% in group 2 (15 eyes), and indocyanine green 0.05% in group 3 (15 eyes). We evaluated visual acuity (VA) and macular sensitivity (MS) preoperatively, 1, 3, and 6 months after surgery. The expression of glial fibrillary acidic protein (GFAP) and neurofilament protein (NF) was assessed immunohistochemically on the ILMs peeled as markers of glial and neuronal cells.Results: In group 1, both mean VA and MS were significantly better at 1 and 3 months after surgery (P < 0.05), whereas no significant difference was found after 6 months. GFAP and NF expression was significantly lower in group 1 (P < 0.05).Conclusions: The ERM/ILM peeling is thought to rip off the intraretinal tissue, based on the amounts of GFAP and NF in the specimens. The use of lutein dyes reduces iatrogenic stress to the retinal tissue and allows a faster functional recovery in the first 3 months after surgery, suggesting a less iatrogenic adhesion to the retinal tissue. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the morphologic features of the photoreceptor layer (by spectral-domain optical coherence tomography) and functional parameters in patients with a lamellar macular hole. Design: Prospective, multicenter, observational case series. Methods: Fifty-four patients with lamellar macular hole were enrolled in the study. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) testing, MP1 microperimetry, and spectral-domain optical coherence tomography. For each patient, 2 experienced masked observers evaluated the integrity of photoreceptor inner segment/outer segment (IS/OS) junction and external limiting membrane (ELM) line. Results: Spectral-domain optical coherence tomography analysis showed complete integrity of the IS/OS junction and ELM line in 40 eyes (group A), partial or complete disruption of the IS/OS junction with an intact ELM line in 8 eyes (group B), and an alteration of both IS/OS junction and ELM line in 6 eyes (group C). Mean BCVA, total retinal sensitivity, and fixation stability were significantly better in groups A and B than in group C (both P < .05, Tukey–Kramer test), whereas there was no significant difference between groups A and B. Mean central retinal sensitivity was significantly different among all 3 groups (all P < .05, Tukey–Kramer test). The grade of integrity of the foveal photoreceptor layer was correlated significantly with mean BCVA (r = −0.57; P < .001), mean central retinal sensitivity (r = 0.52; P < .001), and total retinal sensitivity (r = 0.44; P < .001). Conclusions: In lamellar macular hole, the morphologic features of the foveal photoreceptor layer consistently are correlated with BCVA and central retinal sensitivity. Preservation of the ELM is related to the maintenance of visual acuity. [Copyright &y& Elsevier]

Background: To evaluate the correlations between anatomical and functional changes after idiopathic epiretinal membrane (iERM) surgery., Methods: In this prospective, observational, single-center study, consecutive patients who underwent iERM peeling were enrolled. Reported data were pre- and postoperative best-corrected visual acuity (BCVA), retinal sensitivity (RS) and fixation stability values on microperimetry, structural macular features on SD-OCT and OCTA. RS of foveal and parafoveal area was analysed and two sub-groups were identified whether RS improved or remained unchanged/worsened after surgery; consequently, vascular perfusion density (VPD) of the same area was studied., Results: Twenty-nine eyes of 29 patients were examined. The post-operative improvement in terms of BCVA, RS and fixation within the central 4 degrees was significant (p < 0.001, p < 0.001, p = 0.001), as well as the foveal thickness and macular volume change/reduction (p < 0.001). The pre-operative superficial VPD, choriocapillaris VPD and capillary free zone (CFZ) area were significantly reduced compared to the fellow healthy eye (p = 0.001, p = 0.02, p < 0.001). Choriocapillaris VPD showed a statistically significant increase after surgery (p < 0.02). Superficial, deep and choriocapillaris VPD of the improved RS group showed a significant increase both in foveal (p = 0.03, p = 0.03, p = 0.01) and parafoveal areas (p = 0.01, p = 0.03, p = 0.001)., Conclusions: We reported a higher VPD in the retinal area that experienced a retinal sensitivity improvement 6 months after ERM surgery. This result objectifies the tight bond between visual function and retinal perfusion in ERM patients., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background : To investigate anatomical and functional changes of the macula caused by epiretinal membrane (ERM) peeling procedures in patients with or without posterior vitreous detachment (PVD). Methods : This is a multicentric prospective observational study on thirty-seven (37) patients affected by symptomatic ERM who underwent 25-gauge pars plana vitrectomy (PPV), induction of a PVD (as needed) and peeling of both the internal limiting membrane (ILM) and ERM. Optical coherence tomography-angiography (OCT-A) ( RS 3000 , Nidek, Japan) and microperimetry ( MP-3 , Nidek, Japan) were performed; central retinal thickness (CRT), foveal avascular zone (FAZ) area and perimeter, vessel density and perfusion density, retinal sensitivity and fixation stability (as a total mean retinal sensitivity (MRS), and MRS in the ellipse area and bivariate contour ellipse area (BCEA)) were recorded at baseline and up to postoperative month 3. Results : Eyes were classified as having complete PVD (51.4%) or incomplete PVD (48.6%). At baseline, patients with incomplete PVD had worse best-corrected distance visual acuity (BCDVA), total MRS, MRS in the ellipse area and BCEA, and higher CRT than patients with complete PVD. At month 3, the differences in BCDVA between the two groups remained statistically significant, with patients with incomplete PVD having worse results (difference: 0.199 logMAR, p < 0.001). The difference in the MRS in the ellipse area was statistically significant at month 3 (-3.378 Db, p = 0.035), with greater improvement in patients with complete PVD. Conclusions : Our study shows that patients with incomplete PVD have worse conditions at baseline than patients with complete PVD, and the differences in visual acuity and retinal sensitivity were maintained postoperatively.

Artificial intelligence (AI)- and deep learning (DL)-based systems have shown significant progress in the field of macular disorders, demonstrating high performance in detecting retinal fluid and assessing anatomical changes during disease progression. This study aimed to validate an AI algorithm for identifying and quantifying prognostic factors in visual recovery after macular hole (MH) surgery by analyzing major optical coherence tomography (OCT) biomarkers. This study included 20 patients who underwent vitrectomy for a full-thickness macular hole (FTMH). The mean diameter of the FTMH was measured at 285.36 ± 97.4 μm. The preoperative best-corrected visual acuity (BCVA) was 0.76 ± 0.06 logMAR, improving to 0.38 ± 0.16 postoperatively, with a statistically significant difference ( p = 0.001). AI software was utilized to assess biomarkers, such as intraretinal fluid (IRF) and subretinal fluid (SRF) volume, external limiting membrane (ELM) and ellipsoid zone (EZ) integrity, and retinal hyperreflective foci (HRF). The AI analysis showed a significant decrease in IRF volume, from 0.08 ± 0.12 mm 3 preoperatively to 0.01 ± 0.01 mm 3 postoperatively. ELM interruption improved from 79% ± 18% to 34% ± 37% after surgery ( p = 0.006), whereas EZ interruption improved from 80% ± 22% to 40% ± 36% ( p = 0.007) postoperatively. Additionally, the study revealed a negative correlation between preoperative IRF volume and postoperative BCVA recovery, suggesting that greater preoperative fluid volumes may hinder visual improvement. The integrity of the ELM and EZ was found to be essential for postoperative visual acuity improvement, with their disruption negatively impacting visual recovery. The study highlights the potential of AI in quantifying OCT biomarkers for managing MHs and improving patient care.

Purpose and Context: We report two cases of optic neuritis following Pfizer-BioNTech COVID-19 vaccination in patients with autoimmune diseases. Post-vaccine optic neuritis, although rare, is reported in the literature and an autoimmune mechanism seems to be involved, especially in genetically predisposed subjects., Method: Report of two cases of optic neuritis following COVID-19 vaccination in patients with autoimmune diseases., Key Results: He novelty of this article is the fact that the two patients had a medical history of autoimmune diseases (Hashimoto thyroiditis and ankylosing spondylitis), a point of interest for research because it is not yet clear whether this could constitute a risk factor for adverse events after vaccination., Conclusions: The reactogenicity of COVID-19 mRNA vaccine in individuals suffering from immune-mediated diseases is yet to be elucidated and it is being increasingly investigated. Our paper supports the hypothesis that patients who are already affected or predisposed to autoimmune or autoinflammatory disorders should be carefully evaluated for the benefits and risks of COVID-19 mRNA vaccination.

Purpose: To evaluate whether frequent vigorous physical activity (PA) is significantly associated with active central serous chorioretinopathy (CSCR) and may represent a risk factor for CSCR., Design: Case-control study., Methods: This was a multicenter study. The patient population comprised consecutive patients with active CSCR and a comparable control group of healthy participants. Both groups were interrogated about their PA using a shortened version of the International Physical Activity Questionnaire. The Ainsworth Compendium of Physical Activities was taken as a reference for the activities requiring vigorous effort and to quantify the energy expended, expressed in metabolic equivalent of task (MET). As a main outcome measure, a moderate/high practice of vigorous PA was opposed to an absent/low practice of vigorous PA in the 2 groups., Results: A total of 105 patients with CSCR and 105 healthy controls were included in the study. Moderate/high vigorous PA was observed in 63.5% of the patients with CSCR and in 26% of the controls (P = .0001). The MET values of vigorous PA were 2173.2 ± 2081.5 in the CSCR group and 1216.3 ± 524 in the control group (P = .029). The potential risk of disease associated with moderate/high vigorous PA was 5.58 (odds ratio; 95% confidence interval 3.01-10.69, P = .0001)., Conclusions: This study demonstrates a significant association of vigorous PA with CSCR, indicating an increased probability of disease by 5.58 times. Frequent and intense PA, with the hypertensive episodes that it entails, can break the precarious hemodynamic balance in the choroid of individuals predisposed to CSCR, thereby favoring choroidal vascular decompensation and active disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To report the wide-field choroidal vascularity up to the mid-equator area in diabetic retinopathy (DR) subjects using wide-field optical coherence tomography (WF-OCT)., Design: Prospective, Cross-sectional study., Participants: Forty-seven eyes of 25 DR subjects., Methods: WF-OCT images (55 degrees) were obtained using Spectralis HRA + OCT (Heidelberg Engineering, Germany) in extremes of gazes in all quadrants and manual montages were created to obtain wide field images up to mid equator. A previously reported semi-automated algorithm was used to calculate choroidal vascularity profile (CVI). Regression analysis was performed to identify the factors influencing CVI., Results: Forty-seven eyes from 25 patients were enrolled in the study. The mean age was 68.4 ± 10.6 years. The refractive error (spherical equivalent) ranged from -2.25 to +3.75 diopters. Most common DR grade among study subjects was moderate NPDR (29.41%) and 74.5% eyes had diabetic macular edema (DME). The mean CVI in the macular area (58.29 ± 3.63) was significantly lower than in any of the other fundus areas (all p  ˂ 0.01). The maximum CVI was seen in the nasal region (66.60 ± 5.61), followed by temporal (65.69 ± 3.81), superior (65.01 ± 4.87), and inferior (63.80 ± 5.42). The vertical macular area had the least coefficient of variation (CV) of CVI (0.06) while the inferior quadrant had the highest CV (0.08)., Conclusion: The current study describes the CVI profile on WF-OCT in DR eyes up to mid-equator. The significant increase of the CVI compared to healthy subjects and its significant regional variations introduce this novel quantitative parameter as a reliable biomarker of the diabetes-induced choroidal microangiopathy.

Aging, chronic oxidative stress, and inflammation are major pathogenic factors in the development and progression of age-related macular degeneration (AMD) with the loss of retinal pigment epithelium (RPE). The human RPE contains a subpopulation of progenitors (i.e., RPE stem cells-RPESCs) whose role in the RPE homeostasis is under investigation. We evaluated the paracrine effects of mature RPE cells exposed to oxidative stress (H 2 O 2 ) on RPESCs behavior through co-cultural, morphofunctional, and bioinformatic approaches. RPESCs showed a decline in proliferation, an increase of the senescence-associated β-galactosidase activity, the acquisition of a senescent-like secretory phenotype (SASP), and the reduction of their stemness and differentiation competencies. IL-6 and Superoxide Dismutase 2 (SOD2) seem to be key molecules in RPESCs response to oxidative stress. Our results get insight into stress-induced senescent-associated molecular mechanisms implicated in AMD pathogenesis. The presence of chronic oxidative stress in the microenvironment reduces the RPESCs abilities, inducing and/or maintaining a pro-inflammatory retinal milieu that in turn could affect AMD onset and progression., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To determine the incidence and risk factors for late-onset ocular hypertension (LOH) after vitrectomy., Methods: From the electronic medical records of consecutive patients who underwent primary vitrectomy, from January 2010 to December 2015, at 5 tertiary vitreoretinal centers in Italy, patient demographics, systemic, ophthalmic, operative, and postoperative data were drawn. Main outcome measure was the presence of LOH, defined as intraocular pressure >21 mmHg detected more than 2 months after vitrectomy on at least 2 consecutive visits., Results: Among 6,048 patients, LOH was found in 294 (4.9%) vitrectomized eyes and in 87 (1.4%) fellow eyes, (chi square; P < 0.001). Multivariable logistic regression showed that significant risk factors for developing LOH included intraoperative triamcinolone use (odds ratio [OR], 7.62; P < 0.001), longer axial length (OR, 1.55; P = 3.023), preoperative higher intraocular pressure (OR, 1.81; P = 0.003), and postvitrectomy pseudophakic/aphakic status (OR, 2.04; P < 0.001). Decision-tree analysis showed that the stronger predictor of LOH was intraoperative triamcinolone use (P < 0.001). Secondary predictors were a preoperative intraocular pressure more than 15 mmHg (P < 0.001) in eyes that use triamcinolone, and postvitrectomy pseudophakic/aphakic status (P = 0.007) in eyes that did not use triamcinolone., Conclusion: Late-onset ocular hypertension occurred in 4.9% of vitrectomized eyes. The main risk factors were intraoperative use of triamcinolone and postvitrectomy pseudophakic/aphakic status.

Purpose: To report clinical features of Susac's syndrome (SS) using optical coherence tomography angiography (OCTA)., Methods: Case report., Results: A 25-year-old Caucasian female with a history of non-pulsatile migraine, tinnitus, and verbal apraxia complaining of peripheral scotoma in left eye due to branch retinal arteriole occlusion (BRAO) was diagnosed as having SS after audiometric test, brain magnetic resonance imaging, and multimodal retinal imaging. Fundus biomicroscopy and fluorescein angiography (FA) revealed the presence of retinal ischemia in the area of BRAO. The OCTA images showed decreased vascular perfusion of both superficial and deep plexuses in the area of the occluded arteriole with increase of vascular density values after treatment with intravenous glucocorticoids, cyclophosphamide, and aspirin., Conclusions: OCTA offers a valid alternative to the standard invasive FA, evaluating vascular perfusion in all capillary plexuses, and monitoring retinal microvascular flow changes during the course of BRAO, without dye injection.

Purpose: The aim of the current study was to compare the quality of vision, contrast sensitivity and patient satisfaction with a biaspheric, segmented, rotationally asymmetric IOL (Lentis Comfort LS-313 MF 15-Oculentis GmbH, Berlin, Germany) as opposed to those of a monofocal IOL., Methods: This prospective single-blind comparative study included two groups of patients affected by bilateral senile cataract who underwent lens extraction and IOL implantation. The first group received a bilateral implantation of a monofocal IOL, and the second group received a bilateral implantation of the Comfort IOL. Twelve months after surgery uncorrected and corrected visual acuity at different distances (30, 50, 70 cm and 4 m), defocus curve and contrast sensitivity were assessed. Patient's satisfaction and spectacle independence were evaluated by mean of the NEI RQL-42 questionnaire., Results: No significant differences were found between the groups in terms of near vision. The group of patients implanted with a Comfort IOL obtained the best results at intermediate distances (50 and 70 cm P < .001). Both groups showed an excellent uncorrected distance visual acuity (4 m). No statistically significant differences were found in terms of corrected near, intermediate and distance visual acuity. Concerning contrast sensitivity, no statistically significant differences between the groups were observed at any cycles per degree. The NEI RQL-42 questionnaire showed statistically significant differences between the group for "near vision" (P = .015), "dependence on correction" (P = .048) and "suboptimal correction" (P < .001) subscales., Conclusion: Our findings indicated that the Comfort IOL +1.5 D provides a good intermediate spectacle independence together with a high quality of vision, with a low amount of subjective symptoms and a contrast sensitivity similar to those obtained with a monofocal IOL.

Purpose: To compare the visual acuity, refractive outcomes, and quality of vision in patients with bilateral implantation of 4 intraocular lenses (IOLs)., Settings: Department of Neurosciences, Biomedicine and Movement Sciences, Eye Clinic, University of Verona, Verona, and Carones Ophthalmology Center, Milano, Italy., Design: Prospective case series., Methods: The study included patients who had bilateral cataract surgery with the implantation of 1 of 4 IOLs as follows: Tecnis 1-piece monofocal (monofocal IOL), Tecnis Symfony extended range of vision (extended-range-of-vision IOL), Restor +2.5 diopter (D) (+2.5 D multifocal IOL), and Restor +3.0 D (+3.0 D multifocal IOL). Visual acuity, refractive outcome, defocus curve, objective optical quality, contrast sensitivity, spectacle independence, and glare perception were evaluated 6 months after surgery., Results: The study comprised 185 patients. The extended-range-of-vision IOL (55 patients) showed better distance visual outcomes than the monofocal IOL (30 patients) and high-addition apodized diffractive-refractive multifocal IOLs (P ≤ .002). The +3.0 D multifocal IOL (50 patients) showed the best near visual outcomes (P < .001). The +2.5 D multifocal IOL (50 patients) and extended-range-of-vision IOL provided significantly better intermediate visual outcomes than the other 2 IOLs, with significantly better vision for a defocus level of -1.5 D (P < .001). Better spectacle independence was shown for the +2.5 D multifocal IOL and extended-range-of-vision IOL (P < .001)., Conclusions: The extended-range-of-vision IOL and +2.5 D multifocal IOL provided significantly better intermediate visual restoration after cataract surgery than the monofocal IOL and +3.0 D multifocal IOL, with significantly better quality of vision with the extended-range-of-vision IOL., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the effect of topical antibiotic prophylaxis on postoperative endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents., Methods: A systematic literature search was performed from inception to March 2016 using PubMed, Medline, Web of Science, Embase, and the Cochrane Library, to identify articles that reported cases of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. We used a pooled analysis to estimate the incidence of cases of endophthalmitis who developed after injections performed with and without topical antibiotic prophylaxis. We used regression analysis to explore the effects of study characteristics on heterogeneity., Results: From our search of electronic databases, we identified and screened 4,561 unique records. We judged 60 articles to have reported findings for cohorts of patients who met our inclusion criteria, (12 arms of randomized clinical trials, 11 prospective cohort studies, and 37 retrospective cohort studies), which included 244 cases of endophthalmitis and 639,391 intravitreal injections of anti-vascular endothelial growth factor agents. The final pooled estimate endophthalmitis proportions were 9/10,000 (95% confidence interval, 7/10,000-12/10,000) in the antibiotic-treated group and 3/10,000 (95% confidence interval, 2/10,000-5/10,000) in the untreated group. The estimated incidence of endophthalmitis with topical antibiotic prophylaxis was approximated three times the incidence without prophylaxis. Random effects regression showed that none of the study characteristics significantly affected the effect size in either group., Conclusion: Topical antibiotic after intravitreal injection of anti-vascular endothelial growth factor agents is associated with a higher risk of endophthalmitis.

Purpose: To compare the changes in postoperative peripapillary retinal nerve fiber layer (p-RNFL) thickness after vitrectomy for epiretinal membrane in eyes with preexisting posterior vitreous detachment (PVD) and eyes with surgically induced PVD., Methods: This study included consecutive patients who underwent 25-gauge vitrectomy for epiretinal membrane. Eyes were divided, according to intraoperative PVD status, into a preexisting PVD group and surgically induced PVD group. Best-corrected visual acuity, p-RNFL thickness, and central retinal thickness were performed before and at 1, 3, and 6 months after surgery., Results: One hundred and twenty eyes of 120 patients were enrolled: 64 eyes in the preexisting PVD group and 56 eyes in the surgically induced PVD group. In the preexisting PVD group at 6 months, the mean global p-RNFL thickness did not change, whereas it was reduced in the temporal sector (P = 0.034). In the surgically induced PVD group at 6 months, significant decreases were observed in global p-RNFL thickness (P = 0.027), temporal (P = 0.021), temporal inferior (P = 0.030), and nasal inferior sectors (P = 0.010). At 6 months, the two groups differed significantly in temporal (P < 0.001) and temporal inferior sectors (P = 0.004). The preoperative mean best-corrected visual acuity improved significantly at 6 months in both groups., Conclusion: Postoperative p-RNFL thickness after vitrectomy for epiretinal membrane tended to decrease in the temporal sector in all eyes and in the temporal inferior and nasal inferior sectors in eyes with surgically induced PVD.

Purpose: To report a case of bilateral acute macular neuroretinopathy (AMN) occurring in a 32-year-old woman, analyzed using the multimodal imaging technique., Case Report: A 32-year-old Caucasian woman presented with 20 days history of acute onset of blurred vision in the right eye. The best-corrected visual acuity (BCVA) was 0.8 and 1.0 in the right and left eyes, respectively. She reported a lower urinary tract infection associated with fever, 7 days before the onset of the ocular symptoms. Serological tests demonstrated the presence of IgM specific for cytomegalovirus (CMV), while all the other laboratory tests were negative. SD-OCT exhibited the disruption of the inner segment-outer segment junction, associated with hyper-reflectivity of a thickened outer plexiform layer overlying such area associated with thinning of the outer nuclear layer. The patient was diagnosed with AMN and received a corticosteroid treatment. During all the follow-up, OCT features did not change, although BCVA improved. Four months after the first visit, we found also in the left eye a subfoveal IS/OS disruption but differently from the right eye, in which the abnormalities persisted during all the follow-up visits, in the left one they disappeared only after a month. The IgM specific for the CMV remained positive during the whole follow-up., Conclusions: To our knowledge, this is the first patient reported with a diagnosis of AMN associated with persisting presence of IgM specific for CMV.

Purpose: To evaluate optical coherence tomography (OCT) modifications of outer retinal layers as determinants for functional recovery after surgery for idiopathic macular hole (IMH)., Methods: This prospective study included 23 eyes of 23 consecutive patients who underwent vitreoretinal surgery for IMH. We excluded patients with other retinal diseases. Baseline and follow-up evaluations at months 3 and 6 included complete ophthalmologic and instrumental evaluations. Functional evaluation was performed by Best Corrected Visual Acuity (BCVA) and Amsler test. Morphologic evaluation was performed by spectral-domain 3D-OCT (Topcon, Tokyo, Japan) for a deep analysis of retinal layers as well as central retinal thickness evaluation. A standard 23-G or 25-G vitreoretinal surgery was performed, completed by posterior hyaloid and inner limiting membrane peeling by means of vital dyes and gas tamponade. Statistical analysis was performed on collected data., Results: The mean BCVA increased significantly from 0.57 ± 0.25 logMAR at baseline to 0.34 ± 0.22 logMAR at month 6. Intraretinal layers modification showed a progressive recomposition of inner segment/outer segment layer in 91% of patients at month 6. Retinal layers recomposition showed a progressive increase in all patients during follow-up from the immediate postoperative control to the last 6-month visit., Conclusions: Optical coherence tomography examination appears useful to investigate visual recovery after macular hole surgery. To ensure postsurgical functional increase, recomposition of all retinal layers, in particular in the outer retina, is mandatory. This process could be slow and not immediately observable during follow-up examinations.

Purpose: The purpose of this prospective study was to investigate the proton-beam-induced changes in apparent diffusion coefficient (ADC) values of ocular melanoma treated with proton-beam therapy (PBT) in patients undergoing long-term magnetic resonance imaging (MRI) follow-up and to assess whether variations in ADC constitute a reliable biomarker for predicting and detecting the response of ocular melanoma to PBT., Methods: Seventeen patients with ocular melanoma treated with PBT were enrolled. All patients underwent conventional MRI and diffusion-weighted imaging (DWI) at baseline and 1, 3, 6, and 18 months after the beginning of therapy. Tumor volumes and ADC values of ocular lesions were measured at each examination. Tumor volumes and mean ADC measurements of the five examination series were compared; correlation of ADC values and tumor regression was estimated., Results: Mean ADC values of ocular melanomas significantly increased already 1 month after therapy whereas tumor volume significantly decreased only 6 months after therapy. Pretreatment ADC value of ocular melanomas and early change in ADC value 1 month after therapy significantly correlated with tumor regression., Conclusions: In ocular melanoma treated with PBT, ADC variations precede volume changes. Both pretreatment ADC and early change in ADC value may predict treatment response, thus expanding the role of DWI from diagnostic to prognostic.

Purpose: To evaluate the demographic, geographic, and race-related variables that account for geographic variability in prevalence rates of age-related macular degeneration (AMD)., Design: Systematic review, meta-regression, and decision-tree analysis., Methods: A systematic literature review of PubMed, Medline, Web of Science, and Embase databases identified population-based studies on the prevalence of AMD published before May 2014. Only population-based studies that took place in a spatially explicit geographic area that could be geolocalized, and used retinal photographs and standardized grading classifications, were included. Latitude and longitude data (geolocalization) and the mean annual insolation for the area where survey took place were obtained. Age-standardized prevalence rates across studies were estimated using the direct standardization method. Correlations between the prevalence of AMD and longitude and latitude were obtained by regression analysis. A hierarchical Bayesian meta-regression approach was used to assess the association between the prevalence of AMD and other relevant factors. We further investigated the interplay between location and these factors on the prevalence of AMD using regression based on conditional-inference decision trees., Results: We observed significant inverse correlations between latitude or longitude, and crude or age-standardized prevalence rates, of early and late AMD (P < .001). Metaregression analysis showed that insolation, latitude, longitude, age, and race have a significant effect on the prevalence rates of early and late AMD (P < .001). Decision-tree analysis identified that the most important predictive variable was race for early AMD (P = .002) and insolation for late AMD (P = .001)., Conclusions: Geographic position and insolation are key factors in the prevalence of AMD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To determine the incidence, risk factors, and outcomes of delayed suprachoroidal hemorrhage after vitrectomy., Design: Retrospective multicenter cohort study., Methods: All consecutive patients who underwent primary vitrectomy, from January 2009 to December 2014, at 4 tertiary vitreoretinal centers in Italy were enrolled. Patient demographics and systemic, ophthalmic, operative, and postoperative data from all centers were extracted from the electronic record system using standardized data collection forms. All eyes that developed delayed suprachoroidal hemorrhage within 48 hours of the end of the vitrectomy were identified as the delayed suprachoroidal hemorrhage group; all other eyes that underwent vitrectomy in the same period, without delayed suprachoroidal hemorrhage, were considered the control group., Results: From a total of 4852 vitrectomy procedures, 39 cases of delayed suprachoroidal hemorrhage (0.8%) were identified. Multivariable logistic regression showed that significant risk factors for developing delayed suprachoroidal hemorrhage included advancing age (odds ratio [OR], 2.22; P < .001), longer axial length (OR, 2.57; P < .001), presence of rhegmatogenous retinal detachment (OR, 3.27; P = .005), extensive intraoperative photocoagulation (OR, 4.94; P < .001), and emesis postoperatively (OR, 24.39; P < .001). Decision-tree analysis showed that the stronger predictors of delayed suprachoroidal hemorrhage were emesis postoperatively (P < .001) and extensive intraoperative photocoagulation (P < .001). After a mean follow-up of 27 ± 8 months, the best-corrected visual acuity decreased from 1.3 preoperatively to 1.6 logarithm of minimal angle of resolution at last follow-up (P < .001)., Conclusions: Delayed suprachoroidal hemorrhage occurs in 0.8% of vitrectomized eyes. The main risk factors are postoperative emesis and intraoperative extensive photocoagulation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Dysfunction of the retinal pigmented epithelium (RPE) is one of the first effects of dry age-related macular degeneration (AMD) with consequent blindness. Hence, patients affected by this retinal disorder could benefit from a cell-based transplantation strategy for RPE. Actually, an effective protocol to approach this problem is lacking, though recently, it has been postulated the existence of a subpopulation of RPE stem cells (RPESCs) derived from adult RPE and able to reconstitute a functional RPE. On the other hand, the evidence related to the differentiative potential of human mesenchymal stem cells (MSCs) is continuously increasing. Among others, amniotic fluid-derived MSCs (AF-MSCs) may be a promising candidate, since these cells are characterized by high proliferation and differentiative potential. In this study, AF-MSCs and RPESCs were isolated, characterized to assay their stemness and induced to neuronal/retinal differentiation; specific RPE markers were then analyzed. Our results indicate that RPESCs are more suitable candidates for RPE replacement than AF-MSCs.

Purpose: This study was undertaken to compare the ultrasound and magnetic resonance imaging parameters of ocular melanoma and to assess their variation after proton-beam therapy., Materials and Methods: Fifteen choroidal melanoma patients treated with proton-beam therapy were enroled in the study. All patients underwent ophthalmologic evaluations, ultrasound, conventional magnetic resonance (MR) imaging and diffusion-weighted MR imaging before the start of therapy and 3 and 6 months after therapy. Basal diameters, thickness, internal reflectivity, tumour volumes and apparent diffusion coefficient (ADC) values of ocular melanomas were measured at each examination. Correlations between internal reflectivity and ADC were investigated., Results: No significant changes were seen in tumour diameters and tumour height as assessed by B-scan and A-scan, respectively. Significant increase in mean tumour internal reflectivity was detected at 6 months (baseline 35 % ± 11; 6 months 48 % ± 8, Tukey-Kramer p = 0.005). On MRI, compared to baseline (mean 547 ± 262 mm(3)), a significant reduction in volume was seen at 6 months (Tukey-Kramer p = 0.045) (mean volume 339 ± 170 mm(3), mean reduction 38 %). A significant increase in ADC (baseline 1,002 ± 109 mm(2)/s) was detected both at 3 and 6 months after proton therapy (respectively, 1,454 ± 90 and 1,833 ± 261 mm(2)/s, both p < 0.001)., Conclusions: By MRI, in particular by ADC assessment, it is possible to detect early variations in melanoma treated by proton-beam therapy. This examination could be used together with ultrasound in the follow-up of this treatment.

To investigate the effect of aflibercept in a rare case of choroidal neovascularization (CNV) secondary to choroidal osteoma (CO) and refractory to ranibizumab and bevacizumab. A 45-year-old male with CO-related CNV in his left eye received prior two intravitreal 1.25 mg bevacizumab injections and three intravitreal 0.5 mg ranibizumab injections without visual and anatomic improvement. Best-corrected visual acuity assessment, ophthalmic examination, fundus photography, and optical coherence tomography (OCT) were performed. Switching to intravitreal injection of 2.0 mg aflibercept was performed. After three loading doses of intravitreal aflibercept, visual acuity of the left eye improved from 20/50 to 20/32. Resolution of the persistent subfoveal fluid and reduction of retinal hemorrhage were confirmed according to ophthalmoscopy and OCT findings. No serious adverse events were observed. The treatment effect persisted during a 10-month follow-up period. In choroidal osteoma, switching to intravitreal aflibercept injection may be an effective therapeutic option for treatment of CNV refractory to ranibizumab and bevacizumab.

Purpose: The aim of this study was to investigate the utility of diffusion-weighted magnetic resonance (MR) imaging for prediction and early detection of response to proton beam therapy in ocular melanoma., Materials and Methods: Ten ocular melanoma patients treated with proton beam therapy were enrolled in the study. All patients underwent conventional MR imaging and diffusion-weighted imaging (DWI) before the start of therapy, and after 1, 3 and 6 months of therapy. Tumour volumes and apparent diffusion coefficient (ADC) values of ocular lesions were measured at each examination. Tumour volumes and mean ADC measurements of the four examination series were compared; correlation of ADC values and tumour regression was investigated., Results: Mean ADC value of ocular melanomas significantly increased as early as 3 months after therapy; tumour volume significantly decreased as early as 6 months after therapy. The ADC values of ocular melanomas before therapy significantly correlated with tumour regression., Conclusions: DWI may provide an early surrogate biomarker for prediction and early detection of tumour response to eye-preserving therapies in ocular melanoma.

Objectives: The aim of this paper is to present two cases of severe idiopathic non-infectious paediatric panuveitis, unresponsive to traditional therapy, successfully treated with Adalimumab (HumiraTM, Abbott Pharmaceutical Inc.) in the long term., Methods: The data of the two cases are presented and the literature is reviewed., Results: At base line, case 1 had 0.2 in the RE and 0.5 in the LE, while case 2 had 0.5 and 0.4 in the RE and LE, respectively. The anterior chamber (AC) of case 1 had 3+ cells and 3+ flare in both eyes, as well as diffuse keratic precipitates (Kps). Case 2 presented 2+ cells and 3+ flare in both eyes, as well as tiny Kps in the inferior part of the endothelium. The Binocular Indirect Ophthalmoscopy (BIO) score was +2 in both eyes of case 1 and case 2 at first examination. After Adalimumab initiation, both patients presented a dramatic resolution of the ocular inflammation, as well as a rapid improvement of the BCVA. Case 1 had 0.8 and 1.0 in the RE and the LE, respectively, while case 2 presented 1.0 in both eyes. At the last visit, both patients presented a quiet uveitis and stable BCVA: case 1 had 0.8 and 1.0 in the RE and the LE, respectively, while case 2 presented 1.0 in both eyes. No side effects were recorded during this time., Conclusions: Adalimumab can be a promising drug for the therapy of severe, refractory paediatric uveitis, although further studies are needed on its application in uveitis.