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This work aims to reveal the microscopic (2–3 micrometer resolution) appearance of human myelinated nerve fibers in vivo for the first time. We analyzed the myelinated retinal nerve fibers of a male patient without other neurological disorders in a non-invasive way using the transscleral optical phase imaging method with adaptive optics. We also analyzed the fellow eye with non-myelinated nerve fibers and compared the results with traditional ocular imaging methods such as optical coherence tomography. We documented the microscopic appearance of human myelin and myelinated axons in vivo. This method allowed us to obtain better details than through traditional ocular imaging methods. We hope these findings will be useful to the scientific community to evaluate neuro-retinal structures through new imaging techniques and more accurately document nerve anatomy and the pathophysiology of this disease. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy with a wide range of manifestations including retinal vasculopathy. This study aimed to analyse retinal vascular involvement in FSHD patients using fundus photographs and optical coherence tomography-angiography (OCT-A) scans, evaluated through artificial intelligence (AI). Thirty-three patients with a diagnosis of FSHD (mean age 50.4 ± 17.4 years) were retrospectively evaluated and neurological and ophthalmological data were collected. Increased tortuosity of the retinal arteries was qualitatively observed in 77% of the included eyes. The tortuosity index (TI), vessel density (VD), and foveal avascular zone (FAZ) area were calculated by processing OCT-A images through AI. The TI of the superficial capillary plexus (SCP) was increased (p < 0.001), while the TI of the deep capillary plexus (DCP) was decreased in FSHD patients in comparison to controls (p = 0.05). VD scores for both the SCP and the DCP results increased in FSHD patients (p = 0.0001 and p = 0.0004, respectively). With increasing age, VD and the total number of vascular branches showed a decrease (p = 0.008 and p < 0.001, respectively) in the SCP. A moderate correlation between VD and EcoRI fragment length was identified as well (r = 0.35, p = 0.048). For the DCP, a decreased FAZ area was found in FSHD patients in comparison to controls (t (53) = −6.89, p = 0.01). A better understanding of retinal vasculopathy through OCT-A can support some hypotheses on the disease pathogenesis and provide quantitative parameters potentially useful as disease biomarkers. In addition, our study validated the application of a complex toolchain of AI using both ImageJ and Matlab to OCT-A angiograms. [ABSTRACT FROM AUTHOR]

Background. Eyes shut homolog (EYS) gene mutations are estimated to affect at least 5% of patients with autosomal recessive retinitis pigmentosa. Since there is no mammalian model of human EYS disease, it is important to investigate its age-related changes and the degree of central retinal impairment. Methods. A cohort of EYS patients was studied. They underwent full ophthalmic examination as well as assessment of retinal function and structure, by full-field and focal electroretinograms (ERGs) and spectral domain optical coherence tomography (OCT), respectively. The disease severity stage was determined by the RP stage scoring system (RP-SSS). Central retina atrophy (CRA) was estimated from the automatically calculated area of the sub-retinal pigment epithelium (RPE) illumination (SRI). Results. The RP-SSS was positively correlated with age, showing an advanced severity score (≥8) at an age of 45 and a disease duration of 15 years. The RP-SSS was positively correlated with the CRA area. LogMAR visual acuity and ellipsoid zone width, but not ERG, were correlated with CRA. Conclusions. In EYS-related disease, the RP-SSS showed advanced severity at a relative early age and was correlated with the central area of the RPE/photoreceptor atrophy. These correlations may be relevant in view of therapeutic interventions aimed at rescuing rods and cones in EYS-retinopathy. [ABSTRACT FROM AUTHOR]

Background: Retinal dystrophies related to damaging variants in the cadherin-related family member 1 (CDHR1) gene are rare and phenotypically heterogeneous. Here, we report a longitudinal (three-year) structure–function evaluation of a patient with a CDHR1-related retinal dystrophy. Methods: A 14-year-old girl was evaluated between 2019 and 2022. An ophthalmological assessment, including color vision, perimetry, electroretinography, and multimodal imaging of the retina, was performed periodically every six months. Next-generation sequencing disclosed two likely pathogenic/pathogenic variants in the CDHR1 gene, in compound heterozygosity, confirmed by segregation analysis. Results: At first examination, the patient showed a cone–rod pattern retinal dystrophy. Over follow-up, there was a decline of visual acuity and perimetric sensitivity (by ≥0.3 and 0.6 log units, respectively). Visual loss was associated with a progressive increase in inner retinal thickness (by 30%). Outer retina showed no detectable changes over the follow-up. Conclusions: The results indicate that, in this patient with a CDHR1-related cone–rod dystrophy, the progression to severe visual loss was paralleled by a progressive inner retinal thickening, likely a reflection of remodeling. Inner retinal changes over time may be functionally relevant in view of the therapeutic attempts based on gene therapy or stem cells to mitigate photoreceptor loss. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate ocular findings in hereditary transthyretin amyloidosis (ATTRv) pre-symptomatic carriers. Fourteen ATTRv pre-symptomatic carriers, who are patients with positive genetic testing but without signs or symptoms of the disease, were retrospectively evaluated. Retinal morphology was assessed using optical coherence tomography (OCT) and OCT-angiography. Retinal function was evaluated using cone b-wave and photopic negative response (PhNR). Pupillometry and in vivo corneal confocal microscopy (IVCM) were performed. ATTRv pre-symptomatic carriers presented a significantly reduced central macular thickness (CMT) (p = 0.01) and outer nuclear layer (ONL) thickness (p = 0.01) in comparison to normal controls. No differences were found when analyzing sub-foveal choroidal thickness, retinal nerve fiber layer and ganglion cell complex. In comparison to healthy controls, pre-symptomatic carriers presented an attenuated superficial retinal vascular network and a significantly augmented PhNR amplitude (p = 0.01). However, PhNR implicit times, B-wave amplitude and B-wave peak time did not show significant differences in comparison to controls. No differences were found for pupillometric values. All the examined eyes presented alterations in the IVCM. Preclinical ocular structural and functional abnormalities can be found in ATTRv pre-symptomatic carriers. Thus, an extensive ophthalmological evaluation should be included at the baseline visit and during follow-up. Considering the availability of new drugs potentially able to prevent or delay disease progression, the identification of new disease biomarkers appears to be particularly promising. [ABSTRACT FROM AUTHOR]

The long-term effect of intravitreal Fluocinolone acetonide (FAc) on retinal morphology and function in diabetic macular edema (DME) was investigated. Seventeen eyes of twelve consecutive DME patients, treated by intravitreal FAc, were retrospectively evaluated. Retinal morphology was assessed with central macular thickness (CMT). Retinal function was assessed by best-corrected visual acuity (BCVA) and cone b-wave and photopic negative response (PhNR). The main outcome was a mean change in CMT at month 24. The secondary outcomes were changes in cone b-wave and PhNR at month 24. The incidence of adverse events was also recorded. Mean CMT decreased from 406.52 µm (±138.74) at baseline to 310 µm (±130.39) at 24 months (p = 0.008). No significant changes in the other parameters were found. At baseline, BCVA and PhNR amplitude were negatively correlated (r = −0.55) with CMT. At the end of follow-up, the change in CMT was negatively correlated with baseline CMT (r = −0.53, p = 0.03) and positively correlated with baseline PhNR amplitude (r = 0.58, p < 0.01). A significant, long-term reduction in CMT was observed in DME patients after FAc implant. The anti-edema effect tended to be stronger in patients with the poorest baseline retinal morphology (CMT) and function (PhNR). Structure/function correlations might help to characterize the patients who may benefit from this treatment. [ABSTRACT FROM AUTHOR]

Enhanced S-cone syndrome (ESCS) is a rare autosomal recessive retinal degeneration mainly associated with pathogenic variations in the NR2E3 gene. Only a few pathogenic variations in the NRL gene associated with ESCS have been reported to date. Here, we describe the clinical and genetic findings of two unrelated pediatric patients with a novel frameshift homozygous variant in the NRL gene. Fundus examinations showed signs of peripheral degeneration in both patients, more severe in Proband 2, with relative sparing of the macular area. Spectral domain optical coherence tomography (SD-OCT) revealed a significant macular involvement with cysts in Proband 1, and minimal foveal alteration with peripheral retina involvement in Proband 2. Visual acuity was abnormal in both patients, but more severely affected in Proband 1 than Proband 2. The electroretinogram recordings showed reduced scotopic, mixed and single flash cone responses, with a typical supernormal S-cone response, meeting the criteria for a clinical diagnosis of ESCS in both patients. The present report expands the clinical and genetic spectrum of NRL-associated ESCS, and confirms the age-independent variability of phenotypic presentation already described in the NR2E3-associated ESCS. [ABSTRACT FROM AUTHOR]

The measure of the full-field photopic negative response (ff-PhNR) of light-adapted full-field electroretinogram (ff-ERG) allows to evaluate the function of the innermost retinal layers (IRL) containing primarily retinal ganglion cells (RGCs) and other non-neuronal elements of the entire retina. The aim of this study was to acquire functional information of localized IRL by measuring the PhNR in response to multifocal stimuli (mfPhNR). In this case-control observational and retrospective study, we assessed mfPhNR responses from 25 healthy controls and from 20 patients with multiple sclerosis with previous history of optic neuritis (MS-ON), with full recovery of visual acuity, IRL morphological impairment, and absence of morpho-functional involvement of outer retinal layers (ORL). MfPhNR response amplitude densities (RADs) were measured from concentric rings (R) with increasing foveal eccentricity: 0–5° (R1), 5–10° (R2), 10–15° (R3), 15–20° (R4), and 20–25° (R5) from retinal sectors (superior-temporal (ST), superior-nasal (SN), inferior-nasal (IN), and inferior-temporal (IT)); between 5° and 20° and from retinal sectors (superior (S), temporal (T), inferior (I), and nasal (N)); and within 5° to 10° and within 10° and 20° from the fovea. The mfPhNR RAD values observed in all rings or sectors in MS-ON eyes were significantly reduced (p < 0.01) with respect to control ones. Our results suggest that mfPhNR recordings may detect localized IRL dysfunction in the pathologic condition of selective RGCs neurodegeneration. [ABSTRACT FROM AUTHOR]

A correction has been made to Abstract, sentence: best-corrected visual acuity (BCVA) C1 = 49.10 (18.60 SD) and BCVA C2 = 66.67 (16.00 SD, I p i = 0.005) The sentence becomes: best-corrected visual acuity (BCVA) C1 = 66.67 (16.00 SD) and BCVA C2 = 49.10 (18.60 SD, I p i = 0.005). Reference 1 Rizzo S., Savastano A., Lenkowicz J., Savastano M.C., Boldrini L., Bacherini D., Falsini B., Valentini V. Artificial Intelligence and OCT Angiography in Full Thickness Macular Hole. The mean 1-year BVCA for C1 and C2 was 66.67 and 49.1, respectively, with a I t i -test I p i -value equal to 0.005. [Extracted from the article]

Purpose: To evaluate the 1-year visual acuity predictive performance of an artificial intelligence (AI) based model applied to optical coherence tomography angiography (OCT-A) vascular layers scans from eyes with a full-thickness macular hole (FTMH). Methods: In this observational cross-sectional, single-center study, 35 eyes of 35 patients with FTMH were analyzed by OCT-A before and 1-year after surgery. Superficial vascular plexus (SVP) and deep vascular plexus (DVP) images were collected for the analysis. AI approach based on convolutional neural networks (CNN) was used to generate a continuous predictive variable based on both SVP and DPV. Different pre-trained CNN networks were used for feature extraction and compared for predictive accuracy. Results: Among the different tested models, the inception V3 network, applied on the combination of deep and superficial OCT-A images, showed the most significant differences between the two obtained image clusters defined in C1 and C2 (best-corrected visual acuity [BCVA] C1 = 49.10 [±18.60 SD] and BCVA C2 = 66.67 [±16.00 SD, p = 0.005]). Conclusions: The AI-based analysis of preoperative OCT-A images of eyes affected by FTMH may be a useful support system in setting up visual acuity recovery prediction. The combination of preoperative SVP and DVP images showed a significant morphological predictive performance for visual acuity recovery. [ABSTRACT FROM AUTHOR]

Purpose: To assess choriocapillaris vascular density (VD) in healthy and advanced exudative age-related macular degeneration (ae-AMD) patients by new full-range optical coherence tomography angiography (OCT-A). Method: In this observational, cross-sectional study, 21 healthy and 21 ae-AMD eyes, already treated with anti-VEGF, were enrolled. Angio-View retina patterns centered on fovea (6.4 × 6.4 mm) were acquired for all participants using Solix full-range OCT (Optovue Inc., Freemont, CA, USA). The main outcome was to compare choriocapillaris VD between healthy and ae-AMD eyes. Automated measurements of whole image choriocapillaris VD (%) and fovea grid-based (%) were collected for the analysis. Angio-View patterns were used to assess the flow area (mm2) of macular neovascularization (MNV) by contour flow measure algorithm. Best-corrected visual acuity (BCVA) of both groups was also used for the statistical analysis. Results: The mean age was 60.9 (±8.3) in healthy and 73.33 (±15.05) in ae-AMD eyes. The mean BCVA (ETDRS letters) was 98.47 (±1.50) in healthy and 7.04 (±5.96) in ae-AMD eyes. The Mann–Whitney test comparing choriocapillaries VD for whole and fovea healthy and ae-AMD eyes showed statistical significance (p < 0.0001 (t = 4.91; df = 40) and p < 0.0001 (t = 6.84; df = 40), respectively). Regarding, the correlation between MNV and VD of choriocapillaries, neither whole nor fovea areas were statistically significant (F = 0.38 (R2 = 0.01) and 1.68 (R2 = 0.08), respectively). Conclusions: Choriocapillaris VD showed a statistically significant reduction in comparison to healthy eyes in ae-AMD eyes. Choriocapillaris impairment can be seen in the early phase of MNV pathogenesis. [ABSTRACT FROM AUTHOR]

Usher syndrome type 2A (USH2A) is a genetic disease characterized by bilateral neuro-sensory hypoacusia and retinitis pigmentosa (RP). While several methods, including electroretinogram (ERG), describe retinal function in USH2A patients, structural alterations can be assessed by optical coherence tomography (OCT). According to a recent collaborative study, RP can be staged considering visual acuity, visual field area and ellipsoid zone (EZ) width. The aim of this study was to retrospectively determine RP stage in a cohort of patients with USH2A gene variants and to correlate the results with age, as well as additional functional and morphological parameters. In 26 patients with established USH2A genotype, RP was staged according to recent international standards. The cumulative staging score was correlated with patients' age, amplitude of full-field and focal flicker ERGs, and the OCT-measured area of sub-Retinal Pigment Epithelium (RPE) illumination (SRI). RP cumulative score (CS) was positively correlated (r = 0.6) with age. CS was also negatively correlated (rho = −0.7) with log10 ERG amplitudes and positively correlated (r = 0.5) with SRI. In USH2A patients, RP severity score is correlated with age and additional morpho-functional parameters not included in the international staging system and can reliably predict their abnormality at different stages of disease. [ABSTRACT FROM AUTHOR]