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Maria Brambati, Enrico Borrelli, Riccardo Sacconi, Francesco Bandello, Giuseppe Querques Ophthalmology Department, San Raffaele University Hospital, Milan, ItalyCorrespondence: Giuseppe QuerquesDepartment of Ophthalmology, University Vita-Salute San Raffaele, Via Olgettina 60, Milan, ItalyTel +390226432648Fax +390226433643Email giuseppe.querques@hotmail.itAbstract: Choroideremia (CHM) is an X-linked chorioretinal dystrophy characterized by progressive degeneration of the choroid, retinal pigment epithelium and retina. This disease is caused by mutations in the X-linked CHM gene encoding a Ras-related GTPase Rab escort protein (REP)-1, which is extremely important for the retinal function. Clinically, male-affected patients have a progressive reduction in visual acuity. This disease is formally considered incurable, although new promising treatments have been recently introduced. In this article, a review of the salient pathogenetic features of choroideremia, essential for the proper interpretation of therapeutic approaches, is followed by a discussion of the fundamental clinical features of this hereditary disease. Finally, relevant new therapeutic approaches in this disease will be discussed, including gene therapy, stem cells, small molecules, and retinal prosthesis.Keywords: choroideremia, heredodystrophies, gene, therapy, clinical trials, stem cells, gene therapy, small molecules, retinal prosthesis

Objective: This study was aimed primarily at describing the results of aqueous real-time polymerase chain reaction (RT-PCR) and reporting the rate of therapeutic modifications directly attributable to this procedure (profitability). Our secondary outcome was to compare demographic and clinical characteristics between patients with RT-PCR positivity and those with RT-PCR negative results., Design: Retrospective observational study conducted at the Uveitis Service of San Raffaele Hospital (Milan, Italy) between November 2016 and July 2022., Participants: Patients with infectious uveitis suspect (anterior, intermediate, posterior uveitis, or panuveitis)., Methods: Patients with suspected infectious uveitis underwent aqueous RT-PCR for detection of herpes simplex 1 (HSV-1), herpes simplex 2 (HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), and Toxoplasma gondii., Results: Sixty-five eyes of 61 patients (60 ±16 years of age; 54% males) were included. Aqueous RT-PCR tested positive in 58% and negative in 42% of patients. CMV and HSV-1 were the most frequently detected pathogens. RT-PCR confirmed clinical suspicion in 38% of patients and altered the presumed etiologic diagnosis and treatment in 20% of patients. Profitability was associated with CMV positivity. HSV-1 positivity was related to iris atrophy. CMV positivity was correlated with keratic precipitates. Vitritis and retinitis were related to VZV, CMV, and T. gondii detection. Synechiae, retinitis, and neuritis were related to positive tests regardless of the pathogen investigated. Early complications related to paracentesis were rarely reported., Conclusion: Aqueous RT-PCR was a safe semi-invasive tool to confirm a presumptive diagnosis and to change initial suspicion in ambiguous cases of herpetic uveitis. Thus aqueous RT-PCR may alter therapeutic management., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

This study explored the intracellular metabolic variations between 17 strains of Saccharomyces cerevisiae belonging to two different genetic populations: flor and wine yeasts, in the context of alcoholic fermentation. These two populations are closely related as they share the same ecological niche but display distinct genetic characteristics. A protocol was developed for intracellular metabolites extraction and 1 H-NMR analysis. This methodology allowed us to identify and quantify 21 intracellular metabolites at two different fermentation steps: the exponential and stationary phases. This work provided evidence of significant differences in the abundance of intracellular metabolites, which are strain- and time-dependent, thus revealing complex interactions. Moreover, the differences in abundance appeared to be correlated with life-history traits such as average cell size and specific glycolytic flux, which revealed unsuspected phenotypic correlations between metabolite load and fermentation activity., Competing Interests: CV, PM and MB were employed by the Biolaffort. The remaining 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 Vion, Brambati, Da Costa, Richard and Marullo.)

The authors report a case of a male patient affected by macular hole. In particular, a hyperreflective tissue was found on optical coherence tomography (OCT) examination in macular region, just above the retinal pigment epithelium (RPE). OCT angiography (OCTA) did not show the presence of vascular tissue, thus the hyperreflective material was ascribed to primary gliotic tissue. This case highlights the ability for Müller cells placed near macular holes to migrate up to the RPE and to produce gliotic tissue.

Aim: To characterise macular neovascularisation (MNV) developing in eyes affected by geographic atrophy (GA)., Methods: In this multicentric longitudinal study involving three retina referral centres, patients previously affected by GA who developed an active MNV were included. Patients were investigated using structural optical coherence tomography (OCT), fundus autofluorescence, OCT-angiography and dye angiographies. Patients were treated with ProReNata antivascular endothelial growth factor (VEGF) injections and were revaluated after treatment., Results: Among 512 patients previously diagnosed with GA, 40 eyes of 40 patients (mean age 80.8±7.9 years, mean GA area 8.73±7.39 mm 2 ) presented with treatment-naïve exudative MNV (accounting for an estimated prevalence of 7.81%; 5.49 to 10.13, 95% CIs) and thus were included in the analysis. 67.5% of MNVs were classified as type 2 MNV, 25% as type 1, 2.5% as type 3 and 5% as mixed phenotype. In 92.5% of cases, active MNV in GA showed subretinal hyperreflective material with or without evidence of subretinal/intraretinal hyporeflective exudation. During a mean follow-up of 28±25 months, patients were treated with 6.6±6.3 anti-VEGF injections, with 2.9±1.4 injections in the first year of treatment. No patient developed GA enlargement in the area of MNV., Conclusions: MNVs in GA showed different features and therapeutic response in comparison to previously reported features of MNV in age-related macular degeneration (AMD) without GA. For these reasons, the combined phenotype (ie, GA with neovascular AMD) should be considered as a distinct entity in the research and clinical setting., Competing Interests: Competing interests: RS is a consultant for Carl Zeiss Meditec (Dublin, USA), Novartis (Basel, Switzerland). EB is a consultant for Centervue (Padova, Italy), Carl Zeiss Meditec (Dublin, USA), Novartis (Basel, Switzerland). MP is a consultant for Allergan (Irvine, California,USA), Bayer Shering-Pharma (Berlin, Germany), Novartis (Basel, Switzerland), Zeiss (Dublin, USA). EHS is a consultant for Allergan (Irvine, California,USA), Bayer Shering-Pharma (Berlin, Germany), Novartis (Basel, Switzerland), Roche (Basel, Switzerland). FB is a consultant for Alcon (Fort Worth,Texas,USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan (Irvine, California,USA), Farmila-Thea (Clermont-Ferrand, France), Bayer Shering-Pharma (Berlin, Germany), Bausch And Lomb (Rochester, New York, USA), Genentech (San Francisco, California, USA), Hoffmann-La-Roche (Basel, Switzerland), Novagali Pharma (Évry, France), Novartis (Basel, Switzerland), Sanofi-Aventis (Paris, France), Thrombogenics (Heverlee,Belgium), Zeiss (Dublin, USA). GQ is a consultant for Alimera Sciences (Alpharetta, Georgia, USA), Allergan (Irvine, California, USA), Bayer Shering-Pharma (Berlin, Germany), Heidelberg (Germany), Novartis (Basel, Switzerland), Sandoz (Berlin, Germany), Zeiss (Dublin, USA)., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To describe the clinical phenotype of a cohort of patients with Wolfram syndrome (WS), focusing on the pattern of optic atrophy correlated with brain magnetic resonance imaging (MRI) measurements, as compared with patients with OPA1-related dominant optic atrophy (DOA)., Design: Retrospective, comparative cohort study., Methods: We reviewed 25 patients with WS and 33 age-matched patients affected by OPA1-related DOA. Ophthalmologic, neurologic, endocrinologic, and MRI data from patients with WS were retrospectively retrieved. Ophthalmologic data were compared with data from patients with OPA1-related DOA and further analyzed for age dependency dividing patients in age quartiles. In a subgroup of patients with WS, we correlated the structural damage assessed by optical coherence tomography (OCT) with brain MRI morphologic measurements. Visual acuity (VA), visual field mean defect (MD), retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thickness were assessed by OCT and MRI morphologic measurements of anterior and posterior visual pathways., Results: Optic atrophy was present in 100% of patients with WS. VA, MD, and RNFL thickness loss were worse in patients with WS with a faster decline since early age as compared with patients with DOA, who displayed a more stable visual function over the years. Conversely, GCL sectors were overall thinner in patients with DOA since early age compared to patients with WS, in which GCL thickness started to decline later in life. The neuroradiologic subanalysis on 11 patients with WS exhibited bilateral thinning of the anterior optic pathway, especially the prechiasmatic optic nerves and optic tracts. Optic tract thinning was significantly correlated with GCL thickness but not with RNFL parameters., Conclusions: Our results showed a generally more severe and diffuse degeneration of both anterior and posterior visual pathways in patients with WS, with fast deterioration of visual function and structural OCT parameters since early age. The pattern observed with OCT suggests that retinal ganglion cell axonal degeneration (ie, RNFL) precedes cellular body atrophy (ie, GCL) by about a decade. This differs substantially from DOA, in which a more stable visual function is evident with predominant early loss of GCL, indirectly supporting the lack of a primary mitochondrial dysfunction in patients with WS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Collective motion-or flocking-is an emergent phenomena that underlies many biological processes of relevance, from cellular migrations to animal group movements. In this work, we derive scaling relations for the fluctuations of the mean direction of motion and for the static density structure factor (which encodes static density fluctuations) in the presence of a homogeneous, small external field. This allows us to formulate two different and complementary criteria capable of detecting instances of directed motion exclusively from easily measurable dynamical and static signatures of the collective dynamics, without the need to detect correlations with environmental cues. The static one is informative in large enough systems, while the dynamical one requires large observation times to be effective. We believe these criteria may prove useful to detect or confirm the directed nature of collective motion in in vivo experimental observations, which are typically conducted in complex and not fully controlled environments.

Purpose: To investigate the associated features and the surgical outcomes in eyes with microcystoid macular edema (MME) and cone bouquet abnormalities (CBA) undergoing epiretinal membrane peeling., Methods: Retrospective study including patients who underwent pars plana vitrectomy for idiopathic epiretinal membrane. Factors associated with MME and CBA at baseline and their regression were identified with logistic regression models. Postoperative visual acuity was evaluated with linear mixed models from baseline to 12 months. Risk factors for new or worsened macular edema were explored with a Cox regression model., Results: One hundred and eighty-seven eyes are included in this study; 30 eyes (16%) had MME and 53 eyes (28%) had CBA preoperatively. Microcystoid macular edema was associated with severe epiretinal membrane stage (odds ratio [95% confidence interval] = 3.6 [1.3-12.7], P = 0.02); CBA was inversely associated with ectopic inner foveal layer thickness (odds ratio [95% confidence interval] = 0.97 [0.97-0.99] for each 1- μ m EIFL increase, P = 0.006). Eyes with MME had worse visual acuity after epiretinal membrane peeling ( P = 0.01) and were at risk of macular edema worsening (hazard ratio [95% confidence interval] = 2.22 [1.01-5.16], P = 0.04). Older age was associated with MME persistence (odds ratio [95% confidence interval] = 2.46 [1.06-6.82] for each 10-year increase, P = 0.04). No significant associations were found for CBA., Conclusion: Although CBA had no prognostic consequences, MME was associated with suboptimal visual recovery and less efficient control of inflammation after surgery. Degeneration of Müller cells may have an alleged role, and further imaging and functional tests are warranted.

Curcumin has been demonstrated to exhibit photosensitized bactericidal activity. However, the full exploitation of curcumin as a photo-pharmaceutical active principle is hindered by fast deactivation of the excited state through the transfer of the enol proton to the keto oxygen. Introducing an asymmetry in the molecular structure through acting on the phenyl substituents is expected to be a valuable strategy to impair this undesired de-excitation mechanism competing with the therapeutically relevant ones. In this study, two asymmetric curcumin analogs were synthesized and characterized as to their electronic-state transition spectroscopic properties. Fluorescence decay distributions were also reconstructed. Their analysis confirmed the substantial stabilization of the fluorescent state with respect to the parent compound. Nuclear magnetic resonance experiments were performed with the aim of determining the structural features of the keto-enol ring and the strength of the keto-enol hydrogen bond. Electronic structure calculations were also undertaken to elucidate the effects of substitution on the features of the keto-enol semi-aromatic system and the proneness to proton transfer. Finally, their singlet oxygen-generation efficiency was compared to that of curcumin through the 9,10-dimethylanthracene fluorescent assay.

Purpose: To compare peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thickness measurements obtained with spectral domain optical coherence tomography (SD-OCT) and swept-source OCT (SS-OCT) using an OCT-angiography scanning protocol, and their ability to distinguish among patients with glaucoma, glaucoma suspects (GS), and healthy controls (HC)., Methods: Cross-sectional study of 196 eyes (81 glaucoma, 48 GS, and 67 HC) of 119 participants. Participants underwent peripapillary and macular OCT with SD-OCT and SS-OCT. Parameters of interest were average and sector-wise pRNFL and mGCIPL thickness. Inter-device agreement was investigated with Bland-Altman statistics. Conversion formulas were developed with linear regression. Diagnostic performances were evaluated with area under the receiver operating characteristic curves., Results: Both SD-OCT and SS-OCT detected a significant pRNFL and mGCIPL thinning in glaucoma patients compared to HC and GS for almost all study sectors. A strong linear relationship between the two devices was present for all quadrants/sectors (R2 ≥ 0.81, P < 0.001), except for the nasal (R2 = 0.49, P < 0.001) and temporal (R2 = 0.62, P < 0.001) pRNFL quadrants. SD-OCT and SS-OCT measurements had a proportional bias, which could be removed with conversion formulas. Overall, the two devices showed similar diagnostic abilities., Conclusions: Thickness values obtained with SD-OCT and SS-OCT are not directly interchangeable but potentially interconvertible. Both devices have a similar ability to discriminate glaucoma patients from GS and healthy subjects., Translational Relevance: OCT-Angiography scans can be reliably used to obtain structural metrics in glaucoma patients.

Purpose: To report a case of endophthalmitis following bleb needling in a patient previously implanted with a PRESERFLO ® MicroShunt., Methods: Case report., Results: A 40-year-old woman with bilateral malformative glaucoma repeatedly operated on in childhood underwent PRESERFLO ® MicroShunt implantation in her right eye and six needling revisions (NRs) and a surgical revision due to unsatisfactory intraocular pressure (IOP) control due to bleb encapsulation. About 3 months after the surgical revision the bleb encapsulation relapsed and she underwent a further NR with betamethasone. About 4 days after the last NR, she experienced visual acuity reduction and was therefore advised to come immediately to the hospital for an unscheduled visit, showing up with hypopyon and diffuse vitreous haze. A clinical diagnosis of endophthalmitis (later confirmed by bacteria culture tests) was made and she was treated with pars-plana vitrectomy with silicone oil and intravitreal antibiotics. Preoperative visual function was luckily completely restored., Conclusions: Endophthalmitis can occur after NR in an eye with PRESERFLO ® MicroShunt implant which therefore does not prevent reflux of bacteria from a filtering bleb to the anterior chamber.

Introduction: The aim of this study was to investigate changes in macular perfusion in patients affected by diabetic macular edema (DME) and treated with ILUVIEN® (fluocinolone acetonide intravitreal implant) 0.19 mg using optical coherence tomography angiography (OCTA)., Methods: This was a retrospective cohort study that included patients aged > 18 years with type 2 non-proliferative diabetic retinopathy (DR) and DME at baseline. All patients were treated with the ILUVIEN® implant. A minimum of two 6 × 6-mm OCTA scans were required to ensure that all cases had a baseline OCTA and an OCTA performed at 4 months of follow-up. Qualitative and quantitative comparisons were performed., Results: Ten eyes from ten subjects were included in the analysis. Mean (± standard deviation) age of the study cohort was 57.1 ± 8.3 years. Mean parafoveal perfusion density (PD) at baseline was 64.1 ± 1.8% at baseline, increasing to 66.1 ± 2.9% (p = 0.013) at the 4-month follow-up visit. Mean parafoveal PD at baseline was 64.4 ± 2.1%, increasing to 65.2 ± 2.6% (p = 0.024) after 4 months. In the qualitative assessment, 60 regions (10 areas for each subject) were graded to assess changes in retinal perfusion between the baseline and follow-up visits. This assessment revealed that 24 regions (40.0%) were characterized by a qualitative increase in perfusion after treatment, while 22 (36.7%) and 14 (23.3%) regions were featured by a stability and reduction in retinal perfusion, respectively., Conclusion: OCTA analysis detects improvements in macular perfusion after treatment with ILUVIEN®. This improvement in macular perfusion may be associated with corticosteroid-related beneficial effects on leukostasis., (© 2022. The Author(s).)

We report a case of ocular drug toxicity consistent with bilateral Vogt-Koyanagi-Harada (VKH) like disease in a patient with cutaneous melanoma treated with Dabrafenib/Trametinib therapy. A 53-year-old man with a history of metastatic cutaneous melanoma, treated with Dabrafenib/Trametinib, developed a severe acute panuveitis with granulomatous anterior uveitis and multiple serous retinal detachments. The ocular inflammatory reaction was classified as a bilateral Vogt-Koyanagi-Harada disease. Intraocular inflammation resolved after discontinuation of chemotherapeutic agents and aggressive topical and systemic corticosteroid therapy. The present case outlines the importance of recognizing VKH-like syndrome as a possible consequence of therapy with dabrafenib and trametinib.

The pathogenesis of diabetic macular edema (DME) is complex. Persistently high blood glucose activates multiple cellular pathways and induces inflammation, oxidation stress, and vascular dysfunction. Retinal ganglion cells, macroglial and microglial cells, endothelial cells, pericytes, and retinal pigment epithelium cells are involved. Neurodegeneration, characterized by dysfunction or apoptotic loss of retinal neurons, occurs early and independently from the vascular alterations. Despite the increasing knowledge on the pathways involved in DME, only limited therapeutic strategies are available. Besides antiangiogenic drugs and intravitreal corticosteroids, alternative therapeutic options tackling inflammation, oxidative stress, and neurodegeneration have been considered, but none of them has been currently approved., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2021.)

The aim of this study was to measure macular perfusion in patients with type 1 diabetes and no signs of diabetic retinopathy (DR) using volume rendered three-dimensional (3D) optical coherence tomography angiography (OCTA). We collected data from 35 patients with diabetes and no DR who had OCTA obtained. An additional control group of 35 eyes from 35 healthy subjects was included for comparison. OCTA volume data were processed with a previously presented algorithm in order to obtain the 3D vascular volume and 3D perfusion density. In order to weigh the contribution of different plexuses' impairment to volume rendered vascular perfusion, OCTA en face images were binarized in order to obtain two-dimensional (2D) perfusion density metrics. Mean ± SD age was 27.2 ± 10.2 years [range 19-64 years] in the diabetic group and 31.0 ± 11.4 years [range 19-61 years] in the control group (p = 0.145). The 3D vascular volume was 0.27 ± 0.05 mm 3 in the diabetic group and 0.29 ± 0.04 mm 3 in the control group (p = 0.020). The 3D perfusion density was 9.3 ± 1.6% and 10.3 ± 1.6% in diabetic patients and controls, respectively (p = 0.005). Using a 2D visualization, the perfusion density was lower in diabetic patients, but only at the deep vascular complex (DVC) level (38.9 ± 3.7% in diabetes and 41.0 ± 3.1% in controls, p = 0.001), while no differences were detected at the superficial capillary plexus (SCP) level (34.4 ± 3.1% and 34.3 ± 3.8% in the diabetic and healthy subjects, respectively, p = 0.899). In conclusion, eyes without signs of DR of patients with diabetes have a reduced volume rendered macular perfusion compared to control healthy eyes., (© 2021. The Author(s).)

Purpose: To analyze the functional impact of ectopic inner foveal layers (EIFL), along with other clinical and optical coherence tomography biomarkers, on patients with epiretinal membrane (ERM) and preserved foveal layers' segmentation undergoing ERM removal., Methods: Retrospective review of consecutive patients with ERM who underwent pars plana vitrectomy with ERM peeling from December 2018 to December 2019. Baseline factors including age, gender, lens status, phacoemulsification at the time of surgery, tamponade agent, dye used for ERM and internal limiting membrane (ILM) enhancement, ILM peeling, best-corrected visual acuity (BCVA) and central macular thickness (CMT), presence and thickness of EIFL, thickness of outer nuclear layer (ONL), presence of a cotton ball, subfoveal state of photoreceptors, and presence of cystoid macular edema were included in a multivariable model having the BCVA at 12 months as the main outcome. The changes in EIFL and ONL thickness over time were also analyzed., Results: Fifty-one patients (58 eyes, 23 eyes in the no EIFL group, and 35 eyes in the EIFL group) were enrolled. The BCVA significantly improved over 12 months after surgery, regardless of the presence of EIFL (p < 0.001). Eyes with no EIFL had better BCVA at month 3 (p = 0.04), but this difference was no longer detectable at 6 and 12 months. The presence of EIFL was not associated with the final BCVA (p = 0.9), while the CMT at 12 months correlated with EIFL thickness (r = 0.8, p = 0.008)., Conclusion: Patients with EIFL could reach optimal visual acuity in the absence of disorganization of the inner retinal layers but should be warned of potentially longer healing times. None of the morphologic signs included in this study precluded good visual recovery on long-term follow-up., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Systemic hypertension is related to a variety of retinal manifestations. Reported herein is a case of malignant hypertension associated with bilateral foveal neurosensory detachment in a middle age woman with stenosis of the left renal artery. The present case outlines the importance of recognizing ocular manifestations as a possible consequence of life-threatening systemic disease., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aims : To report our five-year experience on vitreoretinal lymphoma (VRL) as a single-center tertiary hospital. Methods : The ophthalmic, cytopathology, and onco-hematologic records of patients with VRL consecutively seen from 2014 to 2019 were reviewed. Results : Fifty-nine eyes of 31 patients with large B-cell VRL were included. Eighty-one percent has developed central nervous system lymphoma at the end of follow-up. Several different imaging findings were noted, including vitritis, leopard spot appearance, Bruch's membrane/RPE infiltrations, and ellipsoid zone disruption. A variable combination of MYD88-L265P mutation in the aqueous and/or in the vitreous and positive cytology/histology allowed to reach a definite diagnosis in all the patients. Therapies included intravitreal injections of methotrexate and rituximab, systemic chemotherapy, pan-encephalic radiotherapy, and hematopoietic stem cell transplantation. Conclusion : No definite guidelines exist for VRL management. It is crucial to collect as much data as possible from tertiary referral hospitals, which suitably manage a conspicuous number of VRL patients.

Purposes: To describe the prevalence of ocular features among COVID-19 patients and their relationship with clinical data, inflammatory markers and respiratory support therapy (including CPAP); to investigate SARS-CoV-2 in ocular secretions of symptomatic patients., Methods: 172 COVID-19 patients were evaluated for presence of ocular manifestations. Clinical and laboratory data were also reviewed. Conjunctival swabs were analyzed for SARS-CoV-2 by RT-PCR., Results: Forty-five patients (26.2%) reported ocular manifestations. Patients treated with CPAP were more likely to have ocular abnormalities ( p <.01). The presence of ocular symptoms was not associated with more significant alterations on blood tests. Conjunctival swabs from patients with suspect conjunctivitis yielded negative results for SARS-CoV-2., Conclusions: Ocular features are not infrequent in COVID-19 patients, but the presence of SARS-CoV-2 in ocular secretions is low. Ocular manifestations in hospitalized COVID-19 patients can also be a consequence of respiratory support therapy. Prevention of possible transmission through ocular secretions is still recommended.

The aim of this study was to report normal measurements of green-emitting fluorophores in the macula of healthy young individuals and to assess the repeatability of these quantitative metrics. To do so, healthy young volunteers were imaged twice (7 ± 3 days apart) using a confocal blue-light fundus autofluorescence (FAF) device with a shorter excitation wavelength (peak at 450 nm) and the capability for separately detecting the red and green components of the emission spectrum. The main outcome measure was the percentage of area occupied by green-emitting fluorophores in the macula. In addition, this measure was performed in separate regions providing a topographical assessment in the foveal, parafoveal and perifoveal regions. Furthermore, the level of agreement between repeated measurements was evaluated. Thirty eyes from 30 healthy volunteers were included in this analysis. Mean age was 26.2 ± 2.8 years (median: 25.0 years; range: 23.0-32.0 years). Median (interquartile range-IQR) area occupied by green-emitting fluorophores was 3.6% (1.9-4.7%) in the macular region. In the topographical analysis, this percentage was higher in the foveal area (median = 33.3%, IQR = 21.9-41.2%), as compared with both the parafoveal (median = 5.3%; IQR = 2.4-8.1%; p < 0.0001) and perifoveal (median = 0.5%, IQR = 0.2-0.8%; p < 0.0001) regions. The coefficient of variation (CV; ranging from 1.1% to 1.7% in the analyzed regions) and the intraclass correlation coefficient (ICC; ranging from 0.93 to 0.97) indicated high levels of repeatability. In conclusion, the assessment of green-emitting fluorophores is repeatable. The distribution of these fluorophores is highest in the foveal region. Assuming that flavin adenine dinucleotide (FAD) emits in the green autofluorescence spectrum, this variability could be secondary to an increased quantity of mitochondria in the foveal region.

Purpose: To evaluate demographic, clinical, imaging, and genetic factors associated with retinal pigment epithelium enlargement in Stargardt disease (STGD1) and to measure the agreement between short-wavelength fundus autofluorescence (SW-FAF) and near-infrared fundus autofluorescence (NIR-FAF)., Methods: Retrospective cohort study of patients with STGD1 with ≥2 gradable SW-FAF images. RPE-atrophy areas were measured on SW-FAF and NIR-FAF at each visit and regressed against time to obtain the rate of RPE-atrophy enlargement. Agreement between SW-FAF and NIR-FAF with regards to baseline atrophic areas and rates of enlargement was evaluated. Baseline factors predictive of faster SW-FAF RPE-atrophy enlargement were investigated with linear mixed models., Results: Fifty-four eyes of 28 patients (median age: 45 years; 13 males) were included. SW-FAF and NIR-FAF agreed well for slow rates of RPE-atrophy progression, but agreement decreased as the rate increased. Median (interquartile range [IQR]) rate of RPE-atrophy expansion was 0.18 (0.10-0.85) mm 2 /year on SW-FAF and 0.24 (0.08-0.33) mm 2 /year on NIR-FAF. Larger baseline RPE-atrophy area (estimate: 0.057 mm 2 /year, P < 0.001), worse visual acuity (0.305 mm 2 /year, P = 0.005), multifocal disease (0.401 mm 2 /year, P = 0.02), and SW-FAF pattern (0.534 mm 2 /year, P =0 .03) were associated with a faster rate of progression (predictive R 2 : 0.65)., Conclusions: SW-FAF and NIR-FAF are not interchangeable in the evaluation of RPE-atrophy enlargement, and both imaging modalities may be required for optimal detection of disease progression. A multivariable model based on baseline clinical and imaging information may identify patients at higher risk of fast disease progression., Translational Relevance: The knowledge of the agreement of different FAF modalities, the estimated rates of RPE-atrophy enlargement, and factors predictive of faster anatomic decay in STGD1 may allow tailored clinical management and better clinical trials design., Competing Interests: Disclosure: M.V. Cicinelli, None; A. Rabiolo, None; M. Brambati, None; C. Viganò, None; F. Bandello, Allergan (C), Bayer (C), Boehringer-Ingelheim (C), Hoffmann La Roche (C), Novartis (C), NTC Pharma (C), Sifi (C), Thrombogenics (C), Zeiss (C), Sooft (R). M. Battaglia Parodi, None, (Copyright 2020 The Authors.)

The aim of this study was to explore whether rotational three-dimensional (3D) visualization of optical coherence tomography angiography (OCTA) volume data may yield valuable information regarding diabetic retinal microaneurysm (MA) characteristics. In this retrospective, observational study, we collected data from 20 patients (20 eyes) with diabetic retinopathy. Subjects were imaged with the SS-OCTA system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). The OCTA volume data were processed with a volume projection removal algorithm and then exported to imageJ in order to obtain a 3D visualization of the analyzed MAs. The rotational three-dimensional OCTA images were qualitatively and quantitatively investigated. A total of 52 MAs were included in the analysis. On rotational 3D OCTA images, the number of vessels associated with each MA varied between 1 and 4, and most MAs (59.6%) were associated with 2 vessels. Moreover, in 20 MAs (38.4%) these vessels seem to originate from the SCP, while 26 MAs (50.0%) had associated vessels originating from the DVC, and 6 MAs had associated vessels arising from both the SCP and DVC (11.6%). Most MAs (31/52) had a 'saccular' shape. The number of retinal layers occupied by each MA ranged between 1 and 3 and the inner nuclear layer was the retinal layer most frequently occupied by MAs. In conclusion, this study used an algorithm to obtain rotational three-dimensional visualization of retinal MAs. The MAs' architecture is complex and 3D visualization may clarify the true vascular origin of these lesions, which is often mistaken using en face OCTA images.

Various imaging modalities are of significant utility in the screening, grading, treatment, and follow-up of the different stages of diabetic retinopathy (DR) and diabetic macular edema. Color stereographic photography, fluorescein angiography, and optical coherence tomography (OCT) have been the gold standard for DR imaging for years. Besides these tools, newer technologies are gaining validation and popularity, such as fundus autofluorescence and OCT angiography. Furthermore, widefield retinography and ultra-widefield retinography have been introduced for a more comprehensive evaluation of the medium-far and very-far retinal peripheries, which is crucial for the assessment of the diverse manifestations of the disease. The aim of this review is to illustrate the recent advancements of the imaging systems for diagnosing DR, with a focus on the newest and noninvasive diagnostic tools.

Retinal capillary hemangioma (RCH) is a benign retinal tumor defined by a vascular proliferation localized in the peripheral retina, juxtapapillary retina, or the intraneural portion of the optic nerve. In most cases, diagnosis of RCH is performed by fundus evaluation and confirmed by fluorescein fundus angiography. Nevertheless, a small RCH localized on or adjacent to the optic nerve head could be difficult to detect by fundus examination. Here, the authors report an atypical case of RCH, not ophthalmoscopically visible, but successfully detected first by optical coherence tomography (OCT) and then by OCT angiography, which confirmed its vascular nature. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e81-e83.]., (Copyright 2019, SLACK Incorporated.)

Aim: To evaluate the clinical impact of CT scan in modifying the clinical management in patients referred to the emergency department., Methods: We prospectively evaluated 300 patients (177 males, 63 ± 18 years old) admitted in the emergency department (ED) of a single institution, who underwent a CT examination for thoracic and/or abdominal complains. Demographic and clinical data were collected. Hypothesized outcome prior to CT scan and final management (i.e., discharge, short observation in the ED, hospitalization, and department of admission) were compared., Results: After CT examination, a major variation in diagnosis occurred in 37% of cases and clinical management changed in 43%, occurring in 51% of patients who underwent abdominal CT, in 40% of chest CT, and in 29% of chest/abdominal CT (P = 0.015). Department of hospitalization changed in 26% of cases (P < 0.001). Clinical impact of CT scan was significantly associated (P = 0.001) with the color code at admission. In particular, the more severe was the clinical condition, the lower was the variation of management after CT examination., Conclusions: This work confirms the crucial role of CT examination in the management of nontraumatic patients admitted to the ED, both in terms of better clarifying the diagnosis and in influencing the clinical management.