Search

This study aimed to assess outer retinal layer (ORL), retinal pigment epithelium (RPE), choroid (Ch) and choriocapillaris (CC) modifications in adolescents with long-lasting (>10 years) type 1 diabetes (T1D) without (noDR) or with diabetic retinopathy (DR). ORL and RPE thickness were measured at optical coherence tomography (OCT) macular scans. Vascular parameters of Ch and CC were quantified after elaboration of macular OCT-angiography (OCTA) images. Insulin dose and auxological and metabolic parameters were correlated with OCT and OCTA findings in patients. ORL thickness was higher in DR eyes than in noDR and healthy controls (HC), and RPE thickness was higher in noDR and DR eyes than in HC, with statistical significance for some sectors in noDR versus HC. No OCTA parameters of CC and Ch differed among groups, and no significant correlation was observed with auxological and metabolic parameters. In conclusion, ORL and RPE were both increased in adolescents with long-lasting T1D. Such changes were not associated with insulin dose and glycemia control, nor to any choroid or choriocapillaris flow change clinically detectable at OCTA, and they could be potential imaging biomarkers of disease progression. [ABSTRACT FROM AUTHOR]

Purpose: von Hippel-Lindau (VHL) disease is caused by a mutation of the VHL gene and characterized by the development of retinal hemangioblastomas (RH). Current pathophysiologic mechanisms of RH development and progression are still insufficient to predict RH behavior. VHL gene is involved in the cellular response to hypoxia and in many intracellular signaling pathways expressed both in angiogenesis and inflammation. Optical coherence tomography (OCT) allows to identify hyper-reflective retinal foci (HRF) known as aggregates of activated microglial cells as possible in vivo biomarker of local inflammation. The aim of the present study was to investigate the presence of HRF in patients with genetically confirmed VHL disease. Methods: In this cross-sectional study, patients with VHL underwent complete ophthalmological examination and OCT with HRA + OCT Spectralis. HRF were manually identified and calculated in inner (IR), outer (OR) and full retina. Age-matched healthy subjects were enrolled as controls. Results: 113 eyes of 63 VHL patients and 56 eyes of 28 healthy subjects were evaluated. HRF number was significantly higher in VHL than in controls in IR (28.06 ± 7.50 vs 25.25 ± 6.64, p = 0.042). No difference was observed in OR and in full retina (OR: 7.73 ± 2.59 vs 7.95 ± 2.51, p = 0.599; full retina: 35.79 ± 8.77 vs 33.20 ± 7.47, p = 0.093). Conclusion: The increase of HRF, which mirror retinal microglial activation, characterizes VHL eyes. The role of activated microglia in the retina of VHL eyes needs to be better investigated, mainly considering local VHL disease manifestations. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate retinal changes in adolescents with childhood-onset, long-lasting type 1 diabetes mellitus (T1D). Patients and healthy controls (HC) underwent optical coherence tomography (OCT) and OCT-angiography (OCTA). Individual macular layers, peripapillary retinal nerve fiber layer (pRNFL), and vascular parameters (vessel area density (VAD), vessel length fraction (VLF) and vessel diameter index (VDI)) of macular superficial vascular (SVP), intermediate (ICP), deep (DCP) and radial peripapillary capillary plexuses (RPCP) were quantified. Thirty-nine patients (5 with (DR group) and 34 without (noDR group) diabetic retinopathy) and 20 HC were enrolled. The pRNFL and ganglion cell layer (GCL) were thicker in noDR compared to HC and DR, reaching statistically significant values versus HC for some sectors. At the macular level, VAD and VLF were reduced in DR versus HC in all plexuses, and versus noDR in SVP (p < 0.005 for all). At the RPCP level, VAD and VDI were increased in noDR versus HC, significantly for VDI (p = 0.0067). Glycemic indices correlated to retinal parameters. In conclusion, in T1D adolescents, retinal capillary and neuronal changes are present after long-lasting disease, even in the absence of clinical DR. These changes modify when clinical retinopathy develops. The precocious identification of specific OCT and OCTA changes may be a hallmark of subsequent overt retinopathy. [ABSTRACT FROM AUTHOR]

Von Hippel–Lindau (VHL) disease is an autosomal dominant genetic disease caused by VHL gene mutation. Retinal hemangioblastomas (RH) are vascularized tumors and represent the main ocular manifestation of the disease. Histopathologically, RH are composed of capillary vessels and stromal cells, the neoplastic population of the lesion. The origin of these stromal cells remains controversial, even if they are hypothesized to be glial cells. The aim of the present study was to investigate neuronal and microvascular changes of the peripapillary retinal nerve fiber layer, in which glial cells, neurons and capillaries (the radial peripapillary capillary plexus) interact. VHL patients with or without peripheral RH were enrolled and compared to healthy controls. Mean peripapillary retinal nerve fiber layer (pRNFL) thickness was measured by means of optical coherence tomography (OCT). The following vascular parameters of the radial peripapillary capillary plexus were quantified using OCT angiography: Vessel Area Density,Vessel Length Fraction, Vessel Diameter Index and Fractal Dimension. One hundred and nine eyes of 61 patients, and 56 eyes of 28 controls were consecutively studied. Mean pRNFL was significantly thinner in VHL eyes without RH versus eyes with RH and controls. Mean pRNFL thickness did not differ between VHL eyes with RH and controls. All OCTA vascular parameters were reduced in VHL eyes with or without RH versus controls, with significative difference for Vessel Diameter Index. The same OCTA parameters did not significantly differ between VHL eyes with or without RH. In VHL eyes without RH, pRNFL thinning may be the consequence of impaired perfusion of the radial peripapillary capillary plexus, while the increase of pRNFL thickness in VHL eyes with RH may depend on possible activation and proliferation of the other RNFL resident cells, the glial cells. [ABSTRACT FROM AUTHOR]

Purpose: To better understand the pathophysiology of geographic atrophy (GA), secondary to age-related macular degeneration, eyes affected by unilateral GA (and CNV in the fellow eye; U-GA group) or by bilateral GA (B-GA group) were evaluated using an integrated morpho-functional approach and quantifying biomarker of retinal macroglial activity. Methods: Patients with U-GA and B-GA and foveal-sparing were consecutively enrolled in a prospective study. All included eyes underwent fundus photography, fundus autofluorescence (FAF), foveal retinal and choroidal thicknesses (RT, CT), contrast sensitivity, best-corrected visual acuity (BCVA), low-luminance VA (LLVA) and low-luminance deficit (LLD), and mesopic and scotopic microperimetry and multifocal electroretinography (mfERG). Glial fibrillary acidic protein (GFAP), biomarker of Müller cell activation, was quantified in the aqueous humor (AH). Results: Forty eyes of 40 patients (18 in the U-GA group and 22 in the B-GA group) were studied. RT, GA area, BCVA, contrast sensitivity, mfERG, and microperimetry (at both background luminances) were not different between groups. CT was significantly thinner in U-GA compared to B-GA group (p = 0.020). Both LLVA and LLD were significantly worse in the B-GA vs U-GA group (p = 0.033 and p = 0.048, respectively). GFAP intraocular concentration was significantly higher in the B-GA group (p = 0.01). Conclusions: Different pathophysiologic mechanisms may be responsible for GA in unilateral (with CNV in the fellow eye) compared to bilateral GA cases. In unilateral cases, a thinner choroid seems to play a key role. Whereas, in bilateral cases, Müller cells and their supported photoreceptors may be primarily involved. [ABSTRACT FROM AUTHOR]

The authors developed a new surgical technique of retropupillary implantation of an iris-claw intraocular lens (RP-ICIOL). RP-ICIOL is an alternative surgical option to the scleral-fixation technique for the treatment of aphakia without capsular support. Several studies have shown that RP-ICIOL is efficient and safe. However, although it is easier to perform than scleral fixation, it presents some critical issues related to the enclavation procedure. The success of the correct enclavation without excessive surgical manipulations, with subsequent pigment dispersion and without pupil distortion, is highly related to the surgical skills of the individual surgeon. The new technique proposed by the authors consists of using a guide needle to facilitate the enclavation, and to make this surgical procedure standard. The new technique was performed in 26 patients affected by aphakia without capsular support with encouraging functional and anatomical results. [ABSTRACT FROM AUTHOR]

Lamellar macular hole (LMH) is a vitreoretinal disorder characterized by an irregular foveal contour, a break in the inner fovea, dehiscence of the inner foveal retina from the outer retina, and the absence of a full-thickness foveal defect with intact foveal photoreceptors. The pathogenesis is only partially known. The advent of high-resolution optical coherence tomography has allowed distinguishing between two types of epiretinal membrane (ERM) associated with LMH: a conventional ERM (commonly found in macular pucker) and an atypical ERM (known by varied names: dense, epiretinal proliferation, or degenerative). These two types of ERM not only influence LMH morphology but also differ in cell and collagen composition. It remains unclear if these two types are indeed two distinct clinical entities or rather two stages of the same macular disorder. Studies of the natural evolution of LMH have not fully resolved this issue and also offered variable results. Surgical treatment leads to excellent anatomical and functional outcomes, but not without risks. This review provides a critical summary of the available data on LMH including some new insights. [ABSTRACT FROM AUTHOR]

Purpose: To compare the foveal avascular zone (FAZ) area measurements produced by different optical coherence tomography angiography (OCTA). Methods: Healthy enrolled volunteers underwent OCTA using 2 different devices: Spectralis HRA+OCTA (Heidelberg Engineering, Heidelberg, Germany) and RS-3000 Advance (Nidek, Gamagori, Japan). Two graders measured FAZ in both superficial (SCP) and deep (DCP) retinal capillary plexuses. The SCP and DCP en face images were visualized automatically segmenting 2 separate slabs defined by the arbitrary segmentation lines created by the software of each OCT device. One grader repeated each measure twice. Results: Fifty-nine eyes were included. The mean FAZ was 0.33 ± 0.09 mm2 at the SCP and 0.57 ± 0.17 mm2 at the DCP measured with RS-3000 versus 0.30 ± 0.08 and 0.35 ± 0.08 mm2, respectively, measured with Spectralis. The measurements of the 2 devices were significantly different (p < 0.0001). The intraoperator agreement was excellent at the SCP (intraclass correlation coefficient, ICC: 0.97 with Spectralis and 0.96 with RS-3000). At the DCP, it was good with Spectralis and fair with RS-3000 (ICC: 0.85 and 0.64, respectively). The interoperator agreement was excellent for Spectralis and good for RS-3000 at the SCP (ICC: 0.97 and 0.93, respectively). It was good at the DCP with both devices (ICC: 0.74 with RS-3000 and 0.81 with Spectralis). Conclusions: FAZ measurements obtained with different OCTA devices differ. These findings should be considered in follow-up studies of patients with retinal vascular diseases. [ABSTRACT FROM AUTHOR]

Purpose To analyse changes in choroidal thickness and retinal sensitivity (Se) in patients with geographic atrophy (GA) with or without choroidal neovascularisation (CNV) in the fellow eye. Participants Patients with bilateral GA (B-GA group) and patients with unilateral GA and CNV in the fellow eye (U-GA group) were followed every 6 months, and enhanced depth imaging optical coherence tomography (OCT), blue and near infrared-wavelength fundus autofluorescence (B- and NIR-FAF), and microperimetry were evaluated. Methods GA area, choroidal thickness, and Se were measured in the eye with GA at baseline and every 6 months up to the last follow-up visit. Results 19 patients (8 in the B-GA group (16 eyes) and 11 in the U-GA group (11 eyes)) were studied. The mean±SD follow-up was 1.66±0.71 years (range 0.74-2.60 years) in the U-GA group, and 1.51±0.86 years (range 0.58-2.95 years) in the B-GA group (p=0.6766). Mean GA area was not significantly different between groups at baseline (p=0.4118 in the B-FA and p=0.6806 in the NIR-FAF) or at follow-up (p=0.5734 in the B-FAF and p=0.8945 in the NIR-FAF). Mean GA area significantly increased in both groups during follow-up (p=0.0050 for B-FAF and p=0.0052 for NIR-FAF in the U-GA group; p=0.0049 for B-FAF and p=0.0072 for NIR-FAF in the B-GA group). Choroidal thickness was significantly greater in the B-GA group compared with the U-GA group both at baseline (mean choroidal thickness 170.5±78.5 μm vs 129.1 ±36.1 μm; p=0.0371) and at last follow-up (173.2 ±86.1 μm vs 123±32.1 μm; p=0.0340). During followup mean choroidal thickness significantly decreased only in the U-GA group (p=0.0276); conversely mean Se significantly decreased only in B-GA group (p=0.0405). Conclusions During follow-up, changes in Se and choroidal thickness differed in patients with GA with or without CNV in the fellow eye. These results identify at least two GA phenotypes, in which the development and progression of GA may be primarily due to different pathophysiologic mechanisms. [ABSTRACT FROM AUTHOR]

Simple Summary: The in vivo optical coherence tomography analysis of the biomarkers of retinal microglia and macroglia in Von Hippel–Lindau disease represents an innovative field of research. The different behavior of these glial cells in Von Hippel–Lindau patients provides new data regarding the pathophysiology of retinal hemangioblastoma, the most common ocular manifestation of this hereditary disorder. Moreover, these biomarkers show a different behavior in Von Hippel–Lindau patients in relation to the presence or absence of retinal hemangioblastoma. Therefore, we can hypothesize that retinal hemangioblastoma is mainly due to the activation of macroglia by previously activated microglial cells. Background: Von Hippel–Lindau (VHL) disease is a neoplastic syndrome caused by a mutation of the VHL tumor suppressor gene. Retinal hemangioblastoma (RH) is a vascularized tumor and represents the most common ocular manifestation of this disease. At the retinal level, VHL protein is able to regulate tumor growth, angiogenic factors, and neuroinflammation, probably stimulating retinal glial cells. The aim of the present study was to analyze in vivo the optical coherence tomography (OCT) biomarkers of retinal macroglia and microglia in a cohort of VHL patients. Methods: The mean thicknesses of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and peripapillary retinal nerve fiber layer (pRNFL) were measured with OCT as biomarkers of retinal macroglia. OCT images were also analyzed to detect and quantify hyperreflective retinal foci (HRF), a biomarker of retinal activated microglia. Results: 61 eyes of 61 VHL patients (22 eyes (36.07%) with peripheral RH and 39 eyes (63.93%) without RH) and 28 eyes of 28 controls were evaluated. pRNFL was thinner in VHL patients (p < 0.05) and in VHL without RH (p < 0.01) compared to controls, and thicker in VHL patients with RH than in those without RH (p < 0.05). The thickness of mRNFL (p < 0.0001) and GCL (p < 0.05) was reduced in VHL patients and in VHL without RH compared to controls, whereas mRNFL (p < 0.0001) and GCL (p < 0.05) were increased in VHL patients with RH compared to those without RH. HRF were significantly higher in number in VHL patients and in VHL without RH, than in controls, and significantly lower (p < 0.05) in the eyes of VHL patients with RH, than in those without RH. Conclusions: The OCT analysis, which detects and allows to quantify the biomarkers of retinal microglia (HRF) and macroglia (pRNFL, mRNFL and GCL), showed a different behavior of these two retinal glial cells populations in VHL patients, related to the presence or absence of peripheral RH. These data allow to hypothesize a novel pathophysiologic pathway of retinal hemangioblastoma in VHL disease. [ABSTRACT FROM AUTHOR]

Purpose To prospectively analyse microperimetry, standard short-wavelength fundus autofluorescent (SWFAF) and near infrared-wavelength FAF (NIR-FAF) changes in eyes with geographic atrophy (GA) secondary to age-related macular degeneration. Methods Twenty consecutive eyes (14 patients) affected by GA were enrolled. Repeated microperimetric examinations and FAF images were obtained over a mean follow-up period of 12.3±4.5 months. Results GA area was always wider on NIR-FAF versus SW-FAF images (5.05±2.40 mm2 vs 4.45±2.41 mm2, p=0.005 baseline; 5.78±2.87 mm2 vs 5.21±2.77 mm2, p<0.0001 follow-up). Mean retinal sensitivity significantly decreased during follow-up from 7.68±3.92 dB to 6.71±4.37 dB (p=0.0013). 47.3% of the relative dense scotomas (⩽5 dB) progressed to dense scotoma (0 dB). Retinal areas showing relative dense scotoma and characterised by hypo-SW-FAF or hyper- NIR-FAF at baseline had a higher risk of evolving to dense scotoma compared with normo-FAF and hyper- FAF on SW-FAF (OR=2.62 and 2.77, respectively), or normo-FAF at NIR-FAF (OR=2.96). Conclusions SW-FAF, compared with NIR-FAF, underestimates GA area at baseline and at follow-up. The enlargement rate of progression based on NIR-FAF is not greater than on SW-FAF. Different SW-FAF and NIR-FAF patterns show different relative risk of progression from relative to dense scotoma. Microperimetry, SW-FAF and NIR-FAF should be combined to obtain adequate morphological and functional prospective information. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate the efficacy and safety of prompt intravitreal triamcinolone acetonide injection (4 mg/0.1 mL) vs intravitreal bevacizumab injection (1.25 mg/0.05 mL) compared with observation in the management of extensive exudative retinal detachment secondary to posterior uveal melanoma. DESIGN: Retrospective, nonrandomized, interventional case series. METHODS: SETTING: Institutional. PATIENTS: Ninetysix patients affected by posterior uveal melanoma with large exudative retinal detachment (>10 mm in largest basal diameter) were included. INTERVENTION: Patients received intravitreal triamcinolone acetonide (32 eyes) or intravitreal bevacizumab (32 eyes) at plaque removal. Thirty-two patients served as controls (observation group). All groups were matched for age, sex, initial tumor thickness and largest basal diameter, largest exudative retinal detachment basal diameter, tumor location, and Bruch membrane rupture. Patients underwent monthly follow-up examinations in the first 6 months and every 3 months thereafter. Follow-up was longer than 24 months. MAIN OUTCOME MEASURE: Exudative retinal detachment resolution (B-scan ultrasonography), steroid-induced cataract, steroid-induced increased IOP. RESULTS: Follow-up was 37 = 7 months. Marked exudative retinal detachment regression was documented in 22 (69%) intravitreal triamcinolone acetonide-treated vs 11 (34%) intravitreal bevacizumab-treated and 9 (28%) untreated eyes (P ≃ .0007 and P ≃ .0001, respectively). No statistical significance was found between intravitreal bevacizumab group vs observation group (P≃ .45) Steroid-induced cataract was observed in 4 intravitreal triamcinolone acetonide-treated patients (12%). Neither steroid-induced increased IOP nor other short- or long-term side effects were documented. CONCLUSION: Intraoperative intravitreal triamcinolone acetonide injection induces earlier and marked exudative retinal detachment resolution after brachytherapy of posterior uveal melanoma. Risk and benefit should be balanced vs steroid-induced cataract. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the ability of confocal scanning laser ophthalmoscope (cSLO) in the retromode imaging modality in detecting retinal changes secondary to exudative age-related macular degeneration (AMD). Methods: Seventeen eyes of 13 consecutive patients affected by CNV secondary to AMD were evaluated with optical coherence tomography (OCT) to detect neuroretinal detachment (NRD), pigment epithelial detachment (PED), cystoid macular edema (CME), and epiretinal membranes (ERM). All eyes were examined with a cSLO equipped with infrared retromode (RM) imaging modality. Infrared and fundus autofluorescence images were also obtained (IR and FAF). The intermethod agreement between OCT and cSLO was evaluated considering single cSLO imaging modality separately (IR, FAF, and RM), and all imaging modalities together. Results: Eight eyes (47 %) had NRD at OCT; intermethod agreement was poor for any single cSLO imaging modality considered separately ( k: 0.14, 0.01, and 0.29 for cSLO IR, FAF, and RM, respectively). Four eyes had PED at OCT (24 %); intermethod agreement was mild for cSLO RM, poor for IR and FAF ( k: 0.51, 0.16, and 0.00, respectively). CME was present in eight eyes (47 %); intermethod agreement was excellent for cSLO RM, poor for IR and FAF ( k: 0.88, 0.38, and 0.26, respectively). ERM was present in three eyes (18 %); intermethod agreement was mild for cSLO IR, poor for FAF, and excellent for RM ( k: 0.59, 0.00, and 0.76, respectively). Conclusions: cSLO RM imaging is a useful and reproducible technique in detecting retinal features associated with CNV, particularly CME. [ABSTRACT FROM AUTHOR]

Aim To compare standard short-wavelength fundus autofluorescence (SW-FAF) and near infraredwavelength fundus autofluorescence (NIR-FAF) in detecting geographic atrophy (GA) secondary to agerelated macular degeneration, and its retinal sensitivity impairment. Methods Twenty-five consecutive patients (36 eyes) affected by GA were studied by means of fundus autofluorescence imaging, using both SW-FAF (excitation: 488 nm, emission >500 nm) and NIR-FAF (excitation: 787 nm, emission >800 nm). All patients underwent microperimetry to assess fixation characteristics and retinal sensitivity. Results In the extrafoveal region, the total hypoautofluorescent (hypo-FAF) area was significantly wider with NIR-FAF than with SW-FAF (8.03±6.68 mm2 vs 7.37±6.34 mm2 respectively; p=0.005). In the foveal area, the total hypo-FAF area was smaller with NIR-FAF than with SW-FAF (0.19±0.03 mm2 versus 0.42±0.12 mm2 respectively; p=0.008). Foveal sparing was larger at NIR-FAF compared with SW-FAF (p=0.021). In nine cases (25%) the site of fixation was hypoautofluorescent on SW-FAF, but normal on NIR-FAF with preserved retinal sensitivity. Conclusions Standard SW-FAF may overestimate GA in the foveal area, correctly detected by NIR-FAF. In the extrafoveal area, SW-FAF may underestimate GA. Standard SW-FAF should be integrated with NIR FAF when detecting and following GA to avoid inconsistent results and misinterpretation, from both a morphological and functional perspective. Microperimetry helps to quantify retinal sensitivity in GA. [ABSTRACT FROM AUTHOR]

To investigate fixation pattern and retinal sensitivity in patients with serpiginous choroiditis (SC). Twenty-eight eyes (14 patients) with SC were evaluated. Best-corrected visual acuity, color fundus photography, fundus autofluorescence, and fluorescein and indocyanine green angiography were performed. Microperimetry was used to assess fixation pattern and retinal sensitivity. Of 28 eyes, 16 (57%) had central, one (4%) poor central, and 11 (39%) eccentric fixation; and 18 (64%) had stable, four (14%) relatively unstable, and six (21%) unstable fixation. In patients with posterior pole symmetrically involved in both eyes, the better eye had stable and central fixation in all cases. Atrophic lesions were characterized by a dense scotoma in all cases, with a relative scotoma at their margins in ten eyes (38%). In two cases of active disease, a dense scotoma correlated to an active lesion could be detected. A relative scotoma was documented in areas not involved by the disease at the posterior pole in eight eyes (28%), and in the peripapillary area in 11 eyes (39%). Quantification of retinal sensitivity and fixation pattern by microperimetry offers new data about the impact of visual impairment in patients with SC. A reduction of retinal sensitivity in an apparently healthy area suggests a wider functional involvement of the retina, undetectable by morphologic evaluation alone. [ABSTRACT FROM AUTHOR]

Purpose. To describe the long term outcome of patients with subfoveal, occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with subthreshold transpupillary thermotherapy. Methods. 82 eyes of 82 consecutive patients with subfoveal occult CNV secondary to AMD were treated with subthreshold transpupillary thermotherapy. Best corrected visual acuity, fundus photography, fluorescein and indocyanine green angiography were performed. Results. All patients have been followed for at least 24 months. At the final follow-up visit, 75.6% of patients had stable or improved visual acuity and 24.4% had worsened visual acuity. No overtreatment side effects were found. Conclusion. Subthreshold transpupillary thermotherapy seems effective in stabilizing visual acuity in patients affected by occult, subfoveal CNV even on a long-term basis. [ABSTRACT FROM AUTHOR]

: ObjectiveTo evaluate choroidal vascular alterations after transpupillary thermotherapy used as the sole treatment for choroidal melanoma.: DesignProspective noncomparative interventional case series.: ParticipantsForty-five eyes of 45 patients affected by malignant choroidal melanoma treated with transpupillary thermotherapy alone with more than 1 year of follow-up.: InterventionTranspupillary thermotherapy was performed through a panfunduscopic contact lens using an 810-nm diode laser.: Main outcome measuresDynamic/static fluorescein and indocyanine green angiography were performed at scheduled intervals (24 hours, at 3-month intervals during the first year, and every 6 months thereafter) after transpupillary thermotherapy. Visual acuity, clinical evaluation, fundus photographs, and ultrasonographic examination were also performed.: ResultsThe mean follow-up was 30.5 months (range, 12–54 months). Changes in the choroidal circulation were always confined within the treatment margins (except in one case) and characterized by occlusion of choriocapillaris (100%), patent medium and/or large choroidal vessels (76%), retinochoroidal anastomosis (11%), and progressive choroidal vascular remodeling (42%). Forty-one cases (91%) showed persistent clinical regression, and four cases (9%) recurred; recurrent cases showed retinochoroidal anastomosis.: ConclusionsTranspupillary thermotherapy is suggested as a new single therapeutic modality in the treatment of selected choroidal melanomas, but more precise eligibility criteria and longer follow-up are mandatory. Patent choroidal circulation, choroidal vascular remodeling, and anastomosis after transpupillary thermotherapy might be helpful to detect recurrent tumors. [Copyright &y& Elsevier]

Histopathologic studies of diabetic choroid suggest that diabetic choroidopathy is a key aspect secondary to diabetes. Recently, hyperreflective choroidal foci (HCF) have been introduced as novel optical coherence tomography (OCT) parameter. The aim of this study was to identify and quantify HCF in diabetic subjects with retinopathy, with or without diabetic macular edema (DME). Eighty-five diabetic subjects with different degrees of DR were enrolled: 37 without DME and 48 with DME. All subjects underwent full ophthalmologic examination including spectral domain optical coherence tomography (OCT). OCT images were analyzed to quantify and localize HCF. Each image was analyzed by two independent, masked examiners. OCT images showed that all subjects (100%) had HCF in the different layers of the choroid. The number of HCF was significantly higher in diabetics with DME versus those without DME (p < 0.0001). HCF showed variable size, shape and location inside the choroid. They were mainly located in choriocapillaris and Sattler's layer, on the edges of blood vessels. The intraobserver and interobserver agreement was almost perfect (ICC >0.9). This study suggests that hyperreflective foci in the choroid of subjects with DR may be accurately identified with structural OCT. Their number significantly increases with the progression of DME. These HCF may represent, as in the retina, a sign of infiltration of inflammatory cells (mainly migrating microglia) into the choroid, according to the hypothesis raised by Jerry Lutty. HCF may confirm in vivo the histopathologic findings suggesting that diabetic choroidopathy may be primarily a neuroinflammatory disorder. • Diabetic choroidopathy is a key aspect secondary to diabetes. • Hyperreflective choroidal foci (HCF) are novel OCT biomarkers. • HCF seems to be a marker of disease severity and progression in diabetic eyes. • HCF is a sign of infiltration of microglial cells from the retina into the choroid. • HCF may confirm that diabetic choroidopathy is a neuroinflammatory disorder. [ABSTRACT FROM AUTHOR]

Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are multifactorial disorders that affect the macula and cause significant vision loss. Although inflammation and neoangiogenesis are hallmarks of DME and nAMD, respectively, they share some biochemical mediators. While inflammation is a trigger for the processes that lead to the development of DME, in nAMD inflammation seems to be the consequence of retinal pigment epithelium and Bruch membrane alterations. These pathophysiologic differences may be the key issue that justifies the difference in treatment strategies. Vascular endothelial growth factor inhibitors have changed the treatment of both diseases, however, many patients with DME fail to achieve the established therapeutic goals. From a clinical perspective, targeting inflammatory pathways with intravitreal corticosteroids has been proven to be effective in patients with DME. On the contrary, the clinical relevance of addressing inflammation in patients with nAMD has not been proven yet. We explore the role and implication of inflammation in the development of nAMD and DME and its therapeutical relevance. [ABSTRACT FROM AUTHOR]

Background: To evaluate macular perfusion in patients with Von Hippel–Lindau (VHL) disease. Methods: VHL patients with or without peripheral retinal hemangioblastomas (RHs) were consecutively enrolled. A group of healthy subjects served as controls. Macular perfusion was analyzed by means of OCT angiography (OCTA) in the superficial vascular plexus (SVP), and in the intermediate (ICP) and deep retinal capillary (DCP) plexuses. The following OCTA parameters were measured: Vessel Area Density (VAD), Vessel Length Fraction (VLF), Vessel Diameter Index (VDI) and Fractal Dimension (FD). Results: Sixty-three VHL patients (113 eyes) and 28 healthy controls (56 eyes) were enrolled. All OCTA quantitative parameters were reduced in VHL patients vs. controls, reaching statistical significance for VAD of the SVP (0.348 ± 0.07 vs. 0.369 ± 0.06, p = 0.0368) and VDI of all plexuses (p < 0.03 for all). No significant differences were detected between eyes without or with peripheral RHs. Conclusions: Macular perfusion is reduced in VHL patients demonstrating retinal vessel changes that are independent of the presence of peripheral RHs. VHL gene mutations disrupt the hypoxia-induced (HIF)/vascular endothelium growth factors (VEGF) pathway and the Notch signaling, both essential for the normal retinal vasculogenesis and angiogenesis. Therefore, an anomalous generalized retinal vascular development may be hypothesized in VHL disease. [ABSTRACT FROM AUTHOR]

Purpose: This study reviews evidence and provides recommendations for the ideal setting of intravitreal injection (IVI) administration of vascular endothelial growth factor (VEGF) inhibitors. Methods: A multi-step approach was employed, including content analysis of regulations and guidelines, a systematic literature review, and an international survey assessing perioperative complications and endophthalmitis incidence in relation to injection settings. The literature review searched PubMed and Cochrane databases from 2006 to 2022, focusing on studies reporting correlations between complications and treatment settings. The survey utilized a web-based questionnaire distributed to clinical sites and the international ophthalmic community, with data managed using electronic capture tools. Results: We reviewed regulations and guidelines from 23 countries across five continents, finding significant variation in IVI administration settings. In most countries, IVI is primarily administered in outpatient clean rooms (96%) or offices (39%), while in others, it is restricted to ambulatory surgery rooms or hospital-based operating theatres (4%). The literature review found that endophthalmitis risk after IVI is generally low (0.01% to 0.26% per procedure), with no significant difference between office-based and operating room settings. The international survey (20 centers, 96,624 anti-VEGF injections) found low overall incidences of severe perioperative systemic adverse events and endophthalmitis, independent of injection settings. Conclusion: No significant differences in perioperative complications were observed among various settings, including operating theatres, ambulatory surgery rooms, offices, hospitals, or extra-hospital environments. Choosing the appropriate clinical setting can optimize patient management, potentially increasing effectiveness, quality, productivity, and capacity. [ABSTRACT FROM AUTHOR]

Objectives: To propose a new technique of a double inverted epiretinal membrane (ERM) and internal limiting membrane (ILM) flap (double flap group) for the treatment of idiopathic lamellar macular hole (LMH) with atypical ERM (AERM) and to compare surgical outcomes to those of the standard technique of ERM and ILM peeling of the fovea including LMH (control group). Methods: AERM was tomographically defined as a medium reflective thickened membrane above the retinal fiber layers without retinal traction signs. A series of patients affected by LMH with AERM were recruited. Preoperative parameters were: intraretinal cysts (IRC), intraretinal splitting diameter, residual foveal thickness, and ellipsoid zone integrity. Postoperative findings were: full-thickness macular hole (FTMH) development, and persistence or new appearance of IRC. Best-corrected visual acuity (BCVA) at baseline, first, third, and sixth postoperative month was evaluated. Results: A total of 48 eyes of 48 patients were included in this study. In the double flap group (30 eyes), a clear improvement of BCVA was noted (p = 0.004), and there were no complications. In the control group (18 eyes), BCVA did not improve and 3 patients developed postoperative FTMH. Conclusions: The double inverted flap technique is associated with better functional recovery compared to the standard technique and reduces the risk of postoperative FTMH development. [ABSTRACT FROM AUTHOR]

The disorganization of retinal inner layers (DRIL) is an optical coherence tomography (OCT) biomarker strictly associated with visual outcomes in patients with diabetic macular edema (DME) whose pathophysiology is still unclear. The aim of this study was to characterize in vivo, using retinal imaging and liquid biopsy, DRIL in eyes with DME. This was an observational cross-sectional study. Patients affected by center-involved DME were enrolled. All patients underwent spectral domain optical coherence tomography (SD-OCT) and proteomic analysis of aqueous humor (AH). The presence of DRIL at OCT was analyzed by two masked retinal experts. Fifty-seven biochemical biomarkers were analyzed from AH samples. Nineteen eyes of nineteen DME patients were enrolled. DRIL was present in 10 patients (52.63%). No statistically significant difference was found between DME eyes with and without DRIL, considering the AH concentration of all the analyzed biomarkers except for glial fibrillary acidic protein (GFAP), a biomarker of Müller cells dysfunction (p = 0.02). In conclusion, DRIL, in DME eyes, seems to strictly depend on a major dysfunction of Müller cells, explaining its role not only as imaging biomarker, but also as visual function Müller cells-related parameter. [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]

Introduction: The aim of this study was to evaluate the current management of RPE65 biallelic mutation-associated inherited retinal degeneration (RPE65-IRD) in Europe since market authorization of voretigene neparvovec (VN, LuxturnaTM) in 2018. By July 2022, over 200 patients have been treated outside the USA, of whom about 90% in Europe. We conducted among all centers of the European Vision Institute Clinical Research Network (EVICR.net) and health care providers (HCPs) of the European Reference Network dedicated to Rare Eye Diseases (ERN-EYE) the second multinational survey on management of IRDs in Europe elaborated by EVICR.net with a special focus on RPE65-IRD. Methods: An electronic survey questionnaire with 48 questions specifically addressing RPE65-IRD (2019 survey 35) was developed and sent by June 2021 to 95 EVICR.net centers and 40 ERN-EYE HCPs and affiliated members. Of note, 11 centers are members of both networks. Statistical analysis was performed with Excel and R. Results: The overall response rate was 44% (55/124); 26 centers follow RPE65 biallelic mutation-associated IRD patients. By June 2021, 8/26 centers have treated 57 RPE65-IRD cases (1–19/center, median 6) and 43 planned for treatment (range 0–10/center, median 6). The overall age range was 3–52 years, and on average 22% of the patients did not (yet) qualify for treatment (range 2–60%/center, median 15%). Main reasons were too advanced (range 0–100, median 75%) or mild disease (range 0–100, median 0). Eighty-three percent of centers (10/12) that follow RPE65 mutation-associated IRD patients treated with VN participate in the PERCEIVE registry (EUPAS31153, http://www.encepp.eu/encepp/viewResource.htm?id=37005). Quality of life and full-field stimulus test improvements had the highest scores of the survey-reported outcome parameters in VN treatment follow-up. Conclusion: This second multinational survey on management of RPE65-IRD by EVICR.net centers and ERN-EYE HCPs in Europe indicates that RPE65-IRD might be diagnosed more reliably in 2021 compared to 2019. By June 2021, 8/26 centers reported detailed results including VN treatment. Main reasons for non-treatment were too advanced or mild disease, followed by absence of 2 class 4 or 5 mutations on both alleles or because of a too young age. Patient satisfaction with treatment was estimated to be high by 50% of the centers. [ABSTRACT FROM AUTHOR]

Introduction: An increasing number of gene-specific therapies are being developed for inherited retinal degenerations (IRDs). Identification of well-characterized patients is an emerging need. We conducted the second multinational survey among the EVICR.net and ERN-EYE members to understand the management and treatment of IRDs in Europe and compared it to the 2019 survey. Methods: An electronic survey questionnaire was developed and sent to 124 clinical centers (25 countries) by June/July 2021. Statistical analysis was performed with Excel and R. Results: The overall response rate was 44% but varied among countries. Only 9% of responding centers do not see IRD patients (2019 survey 14%), 42% follow at least 200 patients per year, 18% follow 500–999, and 2% more than 1,000. Databases exist in 86% of the centers (local 86%; national web based 12%). IRD patients are referred to EVICR.net and ERN-EYE centers mainly by general ophthalmologists, patient self-referral, or medical retina specialists. Most IRD patients are first seen as adults. Signs and symptoms depend on age of onset: in infancy, nystagmus; at older age, night blindness and reduced visual field; reduced visual acuity is described at any age. Comprehensive ophthalmic examination always includes visual acuity and almost always visual field multimodal retinal imaging, electrophysiology, color vision testing, and refraction. Identification of genotypes is successful in 72% of centers in 40–80% of cases (2019 survey 69% of centers). The time for confirmation of the genetic diagnosis varies from 2–4 weeks to 24 months (2019 survey >4 weeks ≤10 years). Genetic testing is covered by public health service in 83%, private health insurance in 29%, research funds in 24%; 5% do not have access to genetic testing (2019 survey 15%). The most striking result is the high increase in the involvement of centers in natural history and gene therapy trials that more than doubled for the latter. Discussion: This second multinational survey on management of IRDs in Europe highlights persistent important differences in the number of IRD patients managed per center, comparable diagnostic work-up, and increasing genotyping in diagnostic laboratories. The important increase in involvement of centers in natural history and gene therapy trials reflects the rapidly evolving field of gene therapy development. The survey provides important follow-up data for researchers, clinicians, caregivers, patient advocate groups, pharmaceutical companies, and investors. [ABSTRACT FROM AUTHOR]

Purpose: To analyse morpho‐functional foveal changes in eyes with lamellar macular hole (LMH) by an integrated assessment of short‐wavelength fundus autofluorescence (SW‐FAF) and microperimetry (SW‐FAF/microperimetry integrated assessment) before and after treatment with a technique of double‐inverted flaps of epiretinal proliferation (EP) and internal limiting membrane (ILM). Methods: Clinical and tomographic parameters were best‐corrected visual acuity (BCVA), LMH size, central retinal thickness (CRT) and outer retinal layer integrity. SW‐FAF/microperimetry integrated assessment allowed to analyse retinal sensitivity (RS) and FAF status of the fovea by an overlay of RS map on SW‐FAF image. Follow‐up was at baseline, 1, 3, 6 and 12 postoperative months. Results: Forty pseudophakic eyes. Hyper‐FAF area was associated with larger LMH size (p = 0.0073) and inversely correlated with CRT (p = 0.021). Lower preoperative RS was observed in hyper‐FAF than normo‐FAF areas (p = 0.0117). External limiting membrane (ELM) defect was associated with worse BCVA (p = 0.0004). After surgery, BCVA improved (p = 0.001) and it was related to ELM recovery (p = 0.00483), hyper‐FAF area decreased (p = 0.001), and RS increased (p = 0.440). Hyper‐FAF points that normalized their FAF were associated with higher RS improvement compared to unchanged points. Conclusion: Short‐wavelength fundus autofluorescence/microperimetry integrated assessment provides important information on the entity of damage of LMH and on postoperative recovery. Double‐inverted EP and ILM flap technique is safe and effective for LMH treatment. [ABSTRACT FROM AUTHOR]

The aim of the study was to validate the performance of the Optomed Aurora® handheld fundus camera in diabetic retinopathy (DR) screening. Patients who were affected by diabetes mellitus and referred to the local DR screening service underwent fundus photography using a standard table-top fundus camera and the Optomed Aurora® handheld fundus camera. All photos were taken by a single, previously unexperienced operator. Among 423 enrolled eyes, we found a prevalence of 3.55% and 3.31% referable cases with the Aurora® and with the standard table-top fundus camera, respectively. The Aurora® obtained a sensitivity of 96.9% and a specificity of 94.8% in recognizing the presence of any degree of DR, a sensitivity of 100% and a specificity of 99.8% for any degree of diabetic maculopathy (DM) and a sensitivity of 100% and specificity of 99.8% for referable cases. The overall concordance coefficient k (95% CI) was 0.889 (0.828–0.949) and 0.831 (0.658–1.004) with linear weighting for DR and DM, respectively. The presence of hypertensive retinopathy (HR) was recognized by the Aurora® with a sensitivity and specificity of 100%. The Optomed Aurora® handheld fundus camera proved to be effective in recognizing referable cases in a real-life DR screening setting. It showed comparable results to a standard table-top fundus camera in DR, DM and HR detection and grading. The Aurora® can be integrated into telemedicine solutions and artificial intelligence services which, in addition to its portability and ease of use, make it particularly suitable for DR screening. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the effects of subfoveal choroidal neovascularizzation (CNV) secondary to age-related macular degeneration (AMD) on macular functional parameters quantified with an automatic fundus perimeter. Methods. 118 eyes of 98 consecutive patients with subfoveal CNV secondary to AMD were evaluated. Best corrected visual acuity (ETDRS charts), fundus photography, and fluorescein angiography were performed. Microperimetry (fundus-related perimetry) was used to quantify macular sensitivity and fixation pattern (location and stability). Results. Of 118 eyes: 26 (21.9%) had central, 18 (15.1%) poor central and 74 (63.0%) eccentric fixation; 31 (26.0%) had stable, 42 (35.6%) relatively unstable and 45 (38.4%) unstable fixation. In 75 eyes (63.4%) a dense central scotoma was found. Angiographic classification of subfoveal CNV (occult versus classic) was not significantly related to fixation pattern (location: P = 0.274; stability: P = 0.385), and presence of dense scotoma (P = 0.41). Conclusion. Microperimetric quantification of macular sensitivity and fixation pattern in eyes with subfoveal CNV secondary to AMD offers new data about the impact of visual impairment in these eyes. Moreover, microperimetry improves the functional evaluation of subfoveal CNV in AMD. [ABSTRACT FROM AUTHOR]

Purpose: This article aims to review the impact of detecting and quantifying intraocular biomarkers (liquid biopsy) in both aqueous and vitreous humor in eyes of people affected by diabetes mellitus. Methods: This is a detailed review about aqueous and/or vitreous humor sampling in human diabetic eyes for proteomic and/or metabolomic analysis contributing to the understanding of the pathophysiology and treatment effects of diabetic retinopathy. Results: Aqueous and vitreous humor molecular biomarkers proved to be directly correlated to each other and valuable to study retinal conditions. Moreover, proteomic and metabolomic analysis showed that the biomarkers of neuroinflammation, neurodegeneration, and vasculopathy are detectable in intraocular fluids and that their concentration changes in different stages of disease, and in response to treatment of all diabetic retinopathy aspects, mainly diabetic macular edema and proliferative retinopathy. Conclusions: Liquid biopsy offers the possibility to improve our knowledge of intraocular eye disease induced by diabetes mellitus. The exact quantification of intraocular biomarkers contributes to the precision medicine approach even in the diabetic retinopathy scenario. The diffusion of this approach should be encouraged to have quantifiable information directly from the human model, which may be coupled with imaging data. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the individual value and the contribution of color fundus photography (CFP) and optical coherence tomography (OCT) in the screening of age-related macular degeneration (AMD) of an unselected population. Methods: CFP and OCT images of 15957 eyes of 8069 subjects older than 55 years, obtained during a population-based screening for AMD using a single diagnostic non-mydriatic imaging device, were analyzed by a blinded examiner. The two techniques were preliminary evaluated considering the dichotomous parameter "gradable/ungradable", then gradable images were classified. CFP were graded according to the standardized classification of AMD lesions. OCT images were also categorized considering the presence of signs of early/intermediate AMD, late AMD, or other retinal diseases. Another blinded operator re-graded 1978 randomly selected images (for both CFP and OCT), to assess test reproducibility. Results: Of the 15957 eyes, 8356 CFP (52.4%) and 15594 (97.7%) OCT scans were gradable. Moreover, most of the eyes with ungradable CFP (7339, 96.6%) were gradable at OCT. AMD signs were revealed in 7.4% of gradable CFP and in 10.4% of gradable OCT images. Moreover, at OCT, AMD signs were found in 1110 (6.9%) eyes whose CFP were ungradable or without AMD (847 and 263 eyes, respectively). The inter-operator agreement was good for the gradable versus ungradable parameter, and optimal for the AMD grading parameter of CFP. The agreement was optimal for all OCT parameters. Conclusions: OCT provided gradable images in almost all examined eyes, compared to limited CFP efficiency. Moreover, OCT images allowed to detect more AMD eyes compared to gradable photos. OCT imaging appears to significantly improve the power of AMD screening in a general, unselected population, compared to CFP alone. [ABSTRACT FROM AUTHOR]

Purpose: To determine if aqueous humour (AH) concentrations of Retinal Pigment Epithelium (RPE)'s biomarkers are modified after subthreshold micropulse laser (SMPL) treatment of diabetic macular edema (DME). Methods: Naïve DME and healthy subjects were enrolled. All DME patients received SMPL treatments (577-nm yellow light, 5%duty cycle of 0.2 s, power 250 mW), according to study protocol. AH of DME eyes was sampled at baseline and periodically after first SMPL treatment. Control eyes were sampled before cataract surgery. Pigment Epithelium Derived Factor (PEDF) and Erythropoietin (EPO) were quantified with glass-chip protein array. Results: Eighteen DME patients (central retinal thickness = 400 µm on Spectral Domain Optical Coherence Tomography (SD-OCT)) and ten controls were enrolled. The main exclusion criteria were high refractive error, proliferative diabetic retinopathy, glaucoma and neurodegenerative disorders. PEDF concentration was decreased in DME patients at baseline versus controls (P=0.012), while EPO was increased (P=0.029). Both molecules' concentrations remained stable during follow-up after treatments, compared with DME-baseline. Conclusions: The AH concentrations of RPE biomarkers were significantly different in DME treatment-naïve eyes versus controls. The expression of PEDF and EPO remained unchanged after treatments with SMPL in DME eyes. These data are relevant for future research and applications of SMPL. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate peripapillary retinal nerve fibre layer (RNFL) thickness, measured by spectral‐domain optical coherence tomography (SD‐OCT), as a surrogate of visual function in a population of paediatric patients affected by optic pathway glioma (OPG) associated with neurofibromatosis type 1 (NF1). Methods: A total of 38 paediatric patients (66 eyes) affected by MRI‐proven OPG were included. Each patient underwent complete ophthalmological examination, including age‐appropriate visual acuity (VA) assessment and RNFL analysis by SD‐OCT. Visual acuity was classified as normal or pathologic using age‐based normative data. Visual acuity was correlated to mean RNFL thickness of the whole peripapillary area and of each single analyzed sector (nasal, superior, temporal, inferior). Results: Visual acuity was normal in 43 (65%) and pathologic in 23 (35%) eyes. Mean parapapillary RNFL thickness of each analyzed sector was significantly lower in eyes with abnormal VA (p < 0.05). The best balanced cut‐off value of global RNFL thickness allowing to discriminate between eyes with normal and pathologic VA was 76.25 μm (91%, 76%, 67% and 94% of sensitivity, specificity, positive and negative predicting value, respectively). Considering best balanced cut‐off values of other analyzed RNFL sectors, the superior (p = 0.0029) and the inferior (p = 0.0024) sectors reached the higher sensitivity (87% and 87%, respectively) and specificity (81% and 79%, respectively). Conclusion: Retinal nerve fibre layer thickness is directly related to VA in children affected by NF1‐related OPG, and should be considered as a potential surrogate marker of VA. Retinal nerve fibre layer thickness cut‐off values can be used in paediatric patients to discriminate false‐positive results obtained by VA measurement. [ABSTRACT FROM AUTHOR]

Objective: Increasing evidence suggest that neuronal damage is an early and diffuse feature of Multiple Sclerosis (MS) pathology. Analysis of the optic pathway may help to clarify the mechanisms involved in grey matter damage in MS. Purpose of our study was to investigate the relationship between inflammation and neurodegeneration and to achieve evidence of trans-synaptic degeneration in the optic pathway in MS at clinical onset. Methods: 50 clinically isolated syndromes/early relapse-onset MS (CIS/eRRMS) with mean disease duration of 4.0±3.5 months, 28 MRI healthy controls (HC) and 31 OCT-HC were studied. Ten patients had optic neuritis at presentation (MSON+), 40 presented with other symptoms (MSON-). MRI examination included 3D-T1, 3D-FLAIR and 3D-DIR sequences. Global cortical thickness (gCTh), pericalcarin CTh (pCTh) and white matter volume (WMV) were analysed by means of Freesurfer on 3D-T1 scans. Optic radiation morphology (OR) and volume (ORV) were reconstructed on the base of the Jülich’s Atlas. White matter lesion volume (WMLV), OR-WMLV and percent WM damage (WMLV/WMV = WMLV% and OR-WMLV/ORV = ORWMLV%) were obtained by 3D-FLAIR image segmentation. 3D-DIR sequences were applied to identify inflammatory lesions of the optic nerve. Optic coherence tomography (OCT) protocol included the analysis of global peripapillary retinal nerve fiber layer (g-RNFL) and the 6 fundus oculi’s sectors (temporal, T-RNFL; temporal superior, TS-RNFL; nasal superior, NS-RNFL; nasal, N-RNFL; nasal inferior, NI-RNFL, temporal inferior, TI-RNFL). The retina of both eyes was analyzed. The eyes of ON+ were further divided into affected (aON+) or not (naON+). Results: No difference in CTh was found between CIS/eRRMS and HC, and between MSON+ and MSON-. Moreover, MSON+ and MSON- did not differ for any WM lesion load parameter. The most significant correlations between RNFL thickness and optic radiation WM pathology were found in MSON+. In these patients, the temporal RNFL inversely correlated to ipsilateral optic radiation WM lesion load (T-RNFL: r -0.7, p<0.05; TS-RNFL: r -0.7, p<0.05), while nasal RNFL inversely correlated to contralateral optic radiation WM lesion load (NI: r -0.8, p<0.01; NS-RNFL: r -0.8, p<0.01). Conclusions: Our findings suggest that in MSON+ the optic pathway is site of a diffuse pathological process that involves both directly and via trans-synaptic degeneration the RNFL. [ABSTRACT FROM AUTHOR]

Purpose To evaluate changes of specific retinal imaging biomarkers [intraretinal hyper-reflective retinal spots: HRS ; subfoveal neuroretinal detachment: SND; and increased foveal autofluorescence: IFAF after intravitreal steroid or anti-vascular endothelial growth factor treatment in diabetic macular oedema ( DME)] as possible indicators of retinal inflammatory condition. Methods Retrospective analysis of images and clinical charts of 49 eyes (49 patients) with DME treated with intravitreal dexamethasone (dexamethasone, 23 eyes) or intravitreal ranibizumab (ranibizumab, 26 eyes). All patients had fundus colour photograph, spectral domain optical coherence tomography (SD OCT) and fundus autofluorescence ( FAF), best-corrected visual acuity ( BCVA) and microperimetry recorded before and 1 month after the end of treatment. Central macular thickness ( CMT), number of HRS and presence of SND were evaluated by SD OCT. Fundus autofluorescence images were evaluated for area of ( IFAF). Retinal sensitivity within 4° and 12° from fovea was quantified by microperimetry. Changes in morphologic and functional parameters were assessed, and correlation was performed by Pearson's correlation. Results Best-corrected visual acuity and CMT improved in all patients, (p < 0.05, for both groups). Mean number of HRS decreased after both treatments (p < 0.0001). Subfoveal neuroretinal detachment resolved in 85.7% dexamethasone-treated eyes (p = 0.014) and in 50% ranibizumab-treated eyes (p = 0.025). Mean IFAF area decreased in both groups, (p < 0.0001, for both). A significantly higher decrease in CMT was observed in dexamethasone- versus ranibizumab-treated eyes, (p = 0.032). In dexamethasone group, higher number of HRS at baseline and larger IFAF were correlated with higher increase in retinal sensitivity; eyes with SND at baseline had major decrease in CMT versus those without SND, (p = 0.003). Conclusion Higher number of HRS, larger area of IFAF and presence of SND may indicate a prevalent inflammatory condition in DME with specific response to targeted treatment. [ABSTRACT FROM AUTHOR]

We agree that also the analysis of the proteomic and metabolomic profiles of aqueous (AH) and vitreous humor (VH) in different stages and types of diabetes and their changes in response to different levels of metabolic control and treatments may be of great interest in the pathophysiology of diabetic eye damage, both from an ophthalmologic and systemic points of view. Dear Editor, We are grateful for the possibility to reply to the comment about our paper "Intraocular fluid biomarkers (liquid biopsy) in human diabetic retinopathy" proposed by Dmuchowska DA et al,. and we thank these authors for their interest in our work (1). Response to comment on "Intraocular fluid biomarkers (liquid biopsy) in human diabetic retinopathy.". [Extracted from the article]

Objectives Antithrombotic treatment for retinal vein occlusion ( RVO) is controversial, although RVO has been surmised as a predictor of a subsequent vascular event. We aimed to evaluate risk factors, the effects of antithrombotic therapy and the occurrence of subsequent vascular events in patients with a first episode of RVO, according to age of RVO onset. Methods In this prospective cohort study, patients with central ( CRVO) and branch RVO ( BRVO) confirmed by fluorescein angiography were studied; they were divided according to age. Cardiovascular risk factors and thrombophilia were evaluated. Anticoagulants or aspirin were given for at least 3 months. Patients were followed every 6-12 months and vascular events were recorded. Results One hundred CRVO and 32 BRVO patients were enrolled. Five of 60 (8.3%) patients <50 yr and 4/72 (5.5%) over 50 yr had a hereditary thrombophilic defect. One or more cardiovascular risk factors were found in 35 (58%) patients of the younger group, and in 66 (91%) of the older group ( P < 0.001). Antithrombotic treatment led to both a satisfactory recanalization of occluded veins and visual acuity improvement especially in younger patients. Vascular events occurred in 19 (14%) cases after 4 ± 3.3 yr from RVO, more frequently in older than in younger patients (22% vs. 5%, P = 0.005). Conclusions Distribution of cardiovascular, but not of thrombophilic risk factors seems to be influenced by age in RVO patients. Patients with a first RVO, especially those >50 yr, are likely at risk of a subsequent vascular event. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate the presence of hyper reflective spots (HRS) in diabetic patients without clinically detectable retinopathy (no DR) or with non proliferative mild to moderate retinopathy (DR) without macular edema, and compare the results to controls. Methods. 36 subjects were enrolled: 12 with no DR, 12 with DR, and 12 normal subjects who served as controls. All studied subjects underwent full ophthalmologic examination and spectral domain optical coherence tomography (SD-OCT). SD-OCT images were analyzed to measure and localize HRS. Each image was analyzed by two independent, masked examiners. Results. The number of HRS was significantly higher in both diabetics without and with retinopathy versus controls (P < 0.05) and in diabetics with retinopathy versus diabetics without retinopathy (P < 0.05). The HRS were mainly located in the inner retina layers (inner limiting membrane, ganglion cell layer, and inner nuclear layer). The intra observer and interobserver agreement was almost perfect (k > 0.9). Conclusions. SD-OCT hyperreflective spots are present in diabetic eyes even when clinical retinopathy is undetectable. Their number increases with progressing retinopathy. Initially, HRS are mainly located in the inner retina, where the resident microglia is present. With progressing retinopathy, HRS reach the outer retinal layer. HRS may represent a surrogate of microglial activation in diabetic retina. [ABSTRACT FROM AUTHOR]

. Purpose: To determine the validity of scanning laser ophthalmoscopy in the retromode (RM-SLO) versus other imaging modalities in the diagnosis of diabetic macular oedema (DME). Methods: Two hundred and sixty-three eyes were examined. Inclusion criteria were any stage of untreated or treated diabetic retinopathy and four imaging modalities of the macula carried out on the same day: time domain optical coherence tomography (OCT), fundus autofluorescence (FAF), RM-SLO and fluorescein angiography (FA). Two masked retinal specialists independently graded all images. Agreement between RM-SLO and OCT, FA and FAF in evaluating the presence and patterns of DME was evaluated by kappa statistics, sensitivity, specificity, observed proportional agreement, and proportional agreement in positive and negative cases. Results: The agreement in evaluating the presence/absence of DME between RM-SLO and OCT, FA and FAF was good: κ = 0.73 (confidence interval; CI, 0.64-0.83), κ = 0.71 (CI, 0.61-0.81) and κ = 0.73 (CI, 0.63-0.83), respectively. The agreement in evaluating cystoid pattern of DME was almost perfect between RM-SLO and OCT, RM-SLO and FA, κ > 0.8; and good between RM-SLO and FAF, κ > 0.7. The agreement in evaluating the presence/absence of subfoveal neuroretinal was almost perfect between RM-SLO and OCT (κ = 0.83; 95% CI, 0.70-0.96). Subfoveal neuroretinal detachment did not show any specific pattern on FA or FAF. Sensitivity and specificity of RM-SLO in evaluating DME was 97.7% and 71.9% versus OCT, 97.4% and 68.1% versus FA and 96.1% and 73.3% versus FAF. Retinal thickness of 233 μm represented the cut-off value to define DME by RM-SLO. Conclusions: The combined use of non-invasive imaging techniques can improve the diagnostic interpretation of different aspects of DME. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate if simple- or multiple-field digital color nonmydriatic (NM) retinal images can replace 7 standard stereoscopic fundus photographs in the screening of diabetic retinopathy (DR). Design: Prospective, masked, comparative case series. Methods: One hundred and eight eyes of 55 diabetics were studied to determine single lesions and to grade clinical levels of DR and diabetic macular edema (DME) using both 1 and 3 NM digital color retinal images compared with the Early Treatment Diabetic Retinopathy Study (ETDRS) 7 standard 35-mm stereoscopic color fundus photographs (7F-ETDRS). All eyes underwent NM 45-degree field images of 1 central field (1F-NM), NM 45-degree field images of 3 fields (3F-NM), and, after pupil dilatation, 30-degree 7F-ETDRS photography. Images were analyzed by 2 independent, masked retinal specialists (S.V. and E.B.), lesion-by-lesion according to the ETDRS protocol and for clinical severity level of DR and DME according to the international classification of DR. Results: Using 7F-ETDRS as the gold standard, agreement was substantial for grading clinical levels of DR and DME (κ = 0.69 and κ = 0.75) vs 3F-NM; moderate for DR level (κ = 0.56) and substantial for DME (κ = 0.66) vs 1F-NM; almost perfect for detecting presence or absence of DR (κ = 0.88) vs both 1F-NM and 3F-NM; and almost perfect for presence or absence of DME (κ = 0.97) vs 3F-NM and substantial (κ = 0.75) vs 1F-NM. Sensitivity and specificity for detecting referable levels of DR were 82% and 92%, respectively, for 3F-NM and 71% and 96%, respectively, for 1F-NM. Conclusions: Three color 45-degree NM fundus fields may be an effective tool in a screening setting to determine critical levels of DR and DME for prompt specialist referral. One central 45-degree image is sufficient to determine absence or presence of DR and DME, but not for grading it. [Copyright &y& Elsevier]

Background: Early age-related macular degeneration (AMD) has been correlated with different functional alterations, but the exact relationship between fundus lesions and overlying sensitivity is not well known. The aim of this study was to compare fundus-related sensitivity (microperimetry) and fundus autofluorescence (FAF) of the macular area with drusen and pigment abnormalities in early AMD. Methods: 13 consecutive patients with early AMD and visual acuity of 20/20 were studied by means of microperimetry, which automatically analyses macular light differential threshold and fixation patterns. Fundus colour photo and FAF of the macular area were recorded on the same day. Microperimetry was exactly (topographically) superimposed over FAF images. Results: Macular sensitivity significantly decreased over large drusen (11 .2 ± 5.6 dB, p<0.0001) and over pigment abnormalities (13.1 ± 3.6 dB, p<0.0001). When both characteristics were present the reduction was greater if compared with its absence (9.6 ± 4.3 versus 15.0 ± 4.5 dB, p<0.0001). Sensitivitity reduction was significant in areas with altered FAF when compared with areas with normal FAF (p<0.0001). Conclusions: Increased FAF in early AMD has a functional correlate exactly quantified by microperimetry. In retinal areas affected by early AMD retinal sensitivity deteriorates, despite good visual acuity. Microperimetry may allow the early detection of functional impairment caused by these lesions. Both microperimetry and FAF may be useful to monitor AMD progression. [ABSTRACT FROM AUTHOR]

Purpose: To report angiographic observations about feeder vessel identification after photodynamic therapy in patients with choroidal neovascularization caused by age-related macular degeneration.Design: Cohort study.Methods: We analyzed fluorescein and indocyanine green dynamic angiography in 156 eyes of 145 patients before and after photodynamic therapy to identify the feeder vessels of the choroidal neovascular membrane.Results: Before photodynamic therapy one or more feeder vessel could be detected in 35 (22.4%) out of 156 eyes with choroidal neovascularization. Three months after photodynamic therapy, a feeder vessel could be identified in 112 (84.2%) out of 133 eyes with persistent choroidal neovascularization. Among these, 16 eyes received direct laser photocoagulation of the feeder vessel and did not need any further photodynamic therapy.Conclusion: Previous photodynamic therapy improves the detection of the feeder vessel of the choroidal neovascularization. A sequential combined therapy (photodynamic and feeder vessel treatment) could be considered as an alternative to multiple photodynamic treatments. [ABSTRACT FROM AUTHOR]

To analyze the early microvascular retinal changes and oscillatory potentials alterations secondary to diabetic retinal damage, 44 eyes of 22 diabetic patients without and with mild diabetic retinopathy (DR) and 18 eyes of 9 healthy controls were examined. All subjects underwent spectral domain optical coherence tomography (SD-OCT), OCT angiography (OCTA), and electroretinography of oscillatory potentials (OPs). At OCTA, vessel area density (VAD), vessel length fraction (VLF), and fractal dimension (FD) were significantly reduced in the superficial vascular plexus (SVP), VLF and FD in the intermediate capillary plexus (ICP), and FD in the deep capillary plexus (DCP) in the diabetic group compared to the control group. The amplitude (A) of OP2, OP3, OP4 and the sum of OPs were significantly reduced in the diabetic group versus the controls, and the last two parameters were reduced also in patients without DR versus the controls. Moreover, in the diabetic group, a significant direct correlation was found between the A of OP1, OP2, OP3 and sOP and the VLF and FD in the SVP, while a statistically significant inverse correlation was found between the A of OP3 and OP4 and the VDI in the ICP and DCP. The reduced oscillatory potentials suggest a precocious involvement of amacrine cells in diabetic eyes, independently of DR presence, and their correlation with vascular parameters underlines the relevance of the crosstalk between these cells and vascular components in the pathophysiology of this chronic disease. [ABSTRACT FROM AUTHOR]

Subthreshold micropulse laser treatment has become a recognized option in the therapeutic approach to diabetic macular edema. However, some yet undefined elements pertaining to its mechanism of action and most effective treatment method still limit its clinical diffusion. We reviewed the current literature on subthreshold micropulse laser treatment, particularly focusing on its effects on the modulation of retinal neuroinflammation. Subthreshold micropulse laser treatment seems to determine a long-term normalization of specific retinal neuroinflammatory metabolic pathways, contributing to the restoration of retinal homeostasis and the curtailing of local inflammatory processes. Optimized and standardized parameters ensure effective and safe treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the long-term efficacy and safety of 577-nm subthreshold micropulse laser (SMPL) treatment in a large population of patients affected by mild diabetic macular edema (DME) in a real-life setting. We retrospectively evaluated 134 eyes affected by previously untreated center-involving mild DME, and treated with 577-nm SMPL, using fixed parameters. Retreatment was performed at 3 months, in case of persistent retinal thickening. Optical coherence tomography (OCT), along with short and near-infrared fundus autofluorescence, were used to confirm long-term safety. At the end of at least one year follow-up, a significant improvement in visual acuity was documented, compared to baseline (77.3 ± 4.5 and 79.4 ± 4.4 ETDRS score at baseline and at final follow-up, respectively), as well as a reduction in the mean retinal thickness of the thickest ETDRS macular sector at baseline. A reduction in the central retinal thickness and the mean thickness of the nine ETDRS sectors was also found, without reaching statistical significance. No patients required intravitreal injections. No adverse effects were detected. This study suggests that 577-nm SMPL is a safe and repeatable treatment for mild DME that may be applied to real-life clinical settings using fixed parameters and protocols. [ABSTRACT FROM AUTHOR]

Background: To evaluate the earliest retinal morphological and functional changes in diabetic eyes without or with early signs of diabetic retinopathy (DR). Methods: Twenty-two eyes with no DR (noDR group), 22 eyes with mild DR (DR group), and 18 healthy nondiabetic eyes (controls) were enrolled. All eyes were studied by means of spectral domain optical coherence tomography (OCT), OCT angiography (OCTA), and multifocal electroretinogram (mfERG). Results: A significantly higher number of OCT hyperreflective intraretinal foci (HRF) was found in both noDR and DR groups versus controls, but not between DR groups. The OCTA parameters of the superficial vascular plexus (SVP) were significantly reduced in the noDR group both versus controls and DR group (p < 0.05). The OCTA parameters of the intermediate capillary plexus (ICP) were significantly reduced in the DR group versus controls. An increased number of altered hexagons on mfERG was found in the noDR versus the DR group (p = 0.0192). Conclusions: Retinal vascular and functional parameters are differently involved in diabetic eyes; major vascular changes in the SVP and functional alterations of the mfERG are present in diabetic eyes with no clinical microvascular signs of DR, while ICP is mainly involved when early ophthalmoscopic signs of DR are present. The integrated use of mfERG and OCTA provides new significant insights into the pathogenesis of diabetic related retinal disease. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the use of high-resolution ultrasonography for detecting choroidal layer abnormalities in eyes with central serous chorioretinopathy (CSC). Design: Prospective observational case series. Method: Optical coherence tomography (OCT) and high-resolution ultrasonography with a 20-MHz immersion probe were performed bilaterally in 10 patients, of whom 5 were affected by unilateral active CSC and 5 by unilateral cystoid macular edema (CME). Ten age-matched control subjects were also investigated. Results: Both OCT and high-resolution ultrasonography showed a macular elevation in eyes with CSC and CME. High-resolution ultrasonography has shown evidence of a nonechogenic linear band under the retinal pigment epithelium in patients affected by CSC. This could be found in neither patients with CME or in control subjects. Conclusion: High-resolution ultrasonography can detect a nonechogenic space consistent with hyperpermeability of choroidal capillaries in eyes with active CSC. Shadowing by an altered retinal pigment epithelium cannot be ruled out, however. [ABSTRACT FROM AUTHOR]

Subthreshold micropulse laser (SMPL) is a tissue-sparing technique whose efficacy is demonstrated for diabetic macular edema (DME) treatment. However, its mechanism of action is poorly known. A prospective observational study was performed on naïve DME patients treated with SMPL, to evaluate the changes of aqueous humor (AH) inflammatory and vaso-active biomarkers after treatments. AH samples of eighteen DME eyes were collected before and after SMPL. Ten non-diabetic AH samples served as controls. Full ophthalmic evaluation, spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography were performed in DME group. Glass chip protein array was used to quantify 58 inflammatory molecules. Central retinal thickness (CRT) and visual acuity were also monitored. Several molecules showed different concentrations in DME eyes versus controls (p value < 0.05). Fas Ligand (FasL), Macrophage Inflammatory Proteins (MIP)-1α, Regulated on Activation Normal T Cell Expressed and Secreted (RANTES) and Vascular Endothelial Growth Factor (VEGF) were increased in DME at baseline versus controls and decreased after SMPL treatments (p < 0.05). CRT reduction and visual acuity improvement were also found. Inflammatory cytokines, mainly produced by the retinal microglia, were significantly reduced after treatments, suggesting that SMPL may act by de-activating microglial cells, and reducing local inflammatory diabetes-related response. [ABSTRACT FROM AUTHOR]