The aim of the study was to characterize retinal atrophy (RA) with progressive retinal atrophy symptoms in mixed breed dogs using ophthalmoscopy, spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG).The study was performed on 13 mixed breed dogs affected by retinal atrophy (11 males and 2 females that were 1.5-14 years old). Depending on the advancement of RA, SD-OCT examinations identified retinal abnormalities ranging from layer disorganisation to advanced atrophy. The most advanced RA occurred ventral to the optic disc. Total retinal thickness in both eyes (mean ± SD) was lower in dogs with RA compared to controls dorsally (77.7 ± 39.5 μm vs 173.5 ± 13.3 μm), ventrally (33.4 ± 29.9 μm vs 139.5 ± 10.8 μm), nasally (65.0 ± 34.5 μm vs 163.9 ± 11.0 μm) and temporally (61.8 ± 41.7 μm vs 171.9 ± 11.1 μm) to the optic disc. In dogs with locally normal architecture of inner retina, loss of definition of outer retinal layers occurred in many regions. Dark and light-adapted ERGs were reduced in 2 dogs with RA and were unrecordable in 11 dogs. Lesions evident in SD-OCT scans of mixed breed dogs affected with retinal atrophy initially appear ventrally to the optic disc and ventro-dorsally in advanced RA. In all mixed breed dogs with retinal atrophy, clinical signs and SD-OCT results correlate with ERG findings.

In the eye, cells from the retinal pigment epithelium (RPE) facing the neurosensory retina exert several functions that are all crucial for long-term survival of photoreceptors (PRs) and vision. Among those, RPE cells phagocytose under a circadian rhythm photoreceptor outer segment (POS) tips that are constantly subjected to light rays and oxidative attacks. The MerTK tyrosine kinase receptor is a key element of this phagocytic machinery required for POS internalization. Recently, we showed that MerTK is subjected to the cleavage of its extracellular domain to finely control its function. In addition, monocytes in retinal blood vessels can migrate inside the inner retina and differentiate into macrophages expressing MerTK, but their role in this context has not been studied yet. We thus investigated the ocular phenotype of MerTK cleavage-resistant (MerTKCR) mice to understand the relevance of this characteristic on retinal homeostasis at the RPE and macrophage levels. MerTKCR retinae appear to develop and function normally, as observed in retinal sections, by electroretinogram recordings and optokinetic behavioral tests. Monitoring of MerTKCR and control mice between the ages of 3 and 18  months showed the development of large degenerative areas in the central retina as early as 4 months when followed monthly by optical coherence tomography (OCT) plus fundus photography (FP)/autofluorescence (AF) detection but not by OCT alone. The degenerative areas were associated with AF, which seems to be due to infiltrated macrophages, as observed by OCT and histology. MerTKCR RPE primary cultures phagocytosed less POS in vitro, while in vivo, the circadian rhythm of POS phagocytosis was deregulated. Mitochondrial function and energy production were reduced in freshly dissected RPE/choroid tissues at all ages, thus showing a metabolic impairment not present in macrophages. RPE anomalies were detected by electron microscopy, including phagosomes retained in the apical area and vacuoles. Altogether, this new mouse model displays a novel phenotype that could prove useful to understanding the interplay between RPE and PRs in inflammatory retinal degenerations and highlights new roles for MerTK in the regulation of the energetic metabolism and the maintenance of the immune privilege in the retina.

OBJECTIVE: To define optical coherence tomography (OCT) biomarkers that precede the development of complete retinal pigment epithelium and outer retinal atrophy (cRORA) at that location in eyes with age-related macular degeneration (AMD).
METHODS: In this retrospective case-control study, patients with dry AMD who had evidence of cRORA and OCT data available for 4 years (48 ± 4 months) prior to the first visit with evidence of cRORA were included. The visit 4 years prior to the development of cRORA was defined as the baseline visit, and the region on the OCT B-scans of future cRORA development was termed the case region. A region in the same eye at the same distance from the foveal center as the case region that did not progress to cRORA was selected as the control region. OCT B-scans at the baseline visit through both the case and control regions were evaluated for the presence of soft and cuticular drusen, drusen with hyporeflective cores (hcD), drusenoid pigment epithelial detachments (PED), subretinal drusenoid deposits (SDD), thick and thin double-layer signs (DLS), intraretinal hyperreflective foci (IHRF), and acquired vitelliform lesions (AVL).
RESULTS: A total of 57 eyes of 41 patients with dry AMD and evidence of cRORA were included. Mean time from the baseline visit to the first visit with cRORA was 44.7 ± 6.5 months. The presence of soft drusen, drusenoid PED, AVL, thin DLS, and IHRF at the baseline visit was all associated with a significantly increased risk of cRORA at that location. Multivariable logistic regression revealed that IHRF (OR, 8.559; p < 0.001), drusenoid PED (OR, 7.148; p = 0.001), and a thin DLS (OR, 3.483; p = 0.021) were independent predictors of development of cRORA at that location.
CONCLUSIONS: IHRF, drusenoid PED, and thin DLS are all local risk factors for the development of cRORA at that same location. These findings would support the inclusion of these features within a more granular staging system defining specific steps in the progression from early AMD to atrophy.

OBJECTIVE: To evaluate choroid plexus (CP) volume as a biomarker for predicting clinical disability and retinal layer atrophy in relapsing remitting multiple sclerosis (RRMS).
METHODS: Ninety-five RRMS patients and 26 healthy controls (HCs) underwent 3 T whole brain MRI, expanded disability status scale (EDSS) and optical coherence tomography (OCT). Fully automated intra-retinal segmentation was performed to obtain the volumes of the retinal nerve fiber layer (RNFL), combined ganglion cell layer -inner plexiform layer (GCIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), total macular volume (TMV) and papillomacular bundle (PMB). Automated segmentation of the CP within the lateral ventricles was performed and the choroid plexus volume (CPV) was normalized by total intracranial volume (TIV). Linear regression analysis and generalized estimating equation (GEE) models were applied to evaluate relationships between nCPV and EDSS, T2 lesion volume, disease duration, and retinal layer volumes, followed by Bonferroni correction analysis for multiple comparisons.
RESULTS: RRMS patients had larger tChPV compared to HCs (p < 0.001). After Bonferroni correction, there was a significant positive correlation between tChPV and EDSS (r2 = 0.25, p = 0.0002), disease duration (r2 = 0.30, p = 0.01), and T2 lesion volume (r2 = 0.39, p = 0.0000). A robust negative correlation was found between tChPV and RNFL (p < 0.001), GCIPL (p = 0.003), TMV (p = 0.0185), PMB (p < 0.0001), G (p = 0.04), T(p = 0.0001).
CONCLUSIONS: Our findings support the association of tChPV with disability and altered retinal integrity in RRMS.

BACKGROUND: Multiple sclerosis cortical lesions are areas of demyelination and neuroaxonal loss. Retinal layer thickness, measured with optical coherence tomography (OCT), is an emerging biomarker of neuroaxonal loss. Studies have reported correlations between cortical lesions and retinal layer thinning in established multiple sclerosis, suggesting a shared pathophysiological process. Here, we assessed the correlation between cortical lesions and OCT metrics at the onset of multiple sclerosis, examining, for the first time, associations with physical or cognitive disability.
OBJECTIVE: To examine the relationship between cortical lesions, optic nerve and retinal layer thicknesses, and physical and cognitive disability at the first demyelinating event.
METHODS: Thirty-nine patients and 22 controls underwent 3T-MRI, optical coherence tomography, and clinical tests. We identified cortical lesions on phase-sensitive inversion recovery sequences, including occipital cortex lesions. We measured the estimated total intracranial volume and the white matter lesion volume. OCT metrics included peripapillary retinal nerve fibre layer (pRNFL), ganglion cell and inner plexiform layer (GCIPL) and inner nuclear layer (INL) thicknesses.
RESULTS: Higher total cortical and leukocortical lesion volumes correlated with thinner pRNFL (B = -0.0005, 95 % CI -0.0008 to -0.0001, p = 0.01; B = -0.0005, 95 % CI -0.0008 to -0.0001, p = 0.01, respectively). Leukocortical lesion number correlated with colour vision deficits (B = 0.58, 95 %CI 0.039 to 1,11, p = 0.036). Thinner GCIPL correlated with a higher Expanded Disability Status Scale (B = -0.06, 95 % CI -1.1 to -0.008, p = 0.026). MS diagnosis (n = 18) correlated with higher cortical and leukocortical lesion numbers (p = 0.004 and p = 0.003), thinner GCIPL (p = 0.029) and INL (p = 0.041).
CONCLUSIONS: The association between cortical lesions and axonal damage in the optic nerve reinforces the role of neurodegenerative processes in MS pathogenesis at onset.

Our study evaluated the morphological and functional outcomes, and the side effects, of voretigene neparvovec (VN) gene therapy for RPE65-mediated inherited retinal dystrophies (IRDs) in 12 eyes (six patients) at the Oxford Eye Hospital with a mean follow-up duration of 8.2 (range 1-12) months. All patients reported a subjective vision improvement 1 month after gene therapy. Best-corrected visual acuity (BCVA) remained stable (baseline: 1.28 (±0.71) vs. last follow-up: 1.46 (±0.60); p = 0.25). Average white Full-Field Stimulus Testing (FST) showed a trend towards improvement (baseline: -4.41 (±10.62) dB vs. last follow-up: -11.98 (±13.83) dB; p = 0.18). No changes in central retinal thickness or macular volume were observed. The side effects included mild intraocular inflammation (two eyes) and cataracts (four eyes). Retinal atrophy occurred in 10 eyes (eight mild, two severe) but did not impact FST measurements during the follow-up period. Increased intraocular pressure (IOP) was noted in three patients (six eyes); four eyes (two patients) required glaucoma surgery. The overall safety and effectiveness of VN treatment in our cohort align with previous VN clinical trials, except for the higher occurrence of retinal atrophy and increased IOP in our cohort. This suggests that raised IOP and retinal atrophy may be more common than previously reported.

UNASSIGNED: Accurately detecting and segmenting areas of retinal atrophy are paramount for early medical intervention in pathological myopia (PM). However, segmenting retinal atrophic areas based on a two-dimensional (2D) fundus image poses several challenges, such as blurred boundaries, irregular shapes, and size variation. To overcome these challenges, we have proposed an attention-aware retinal atrophy segmentation network (ARA-Net) to segment retinal atrophy areas from the 2D fundus image.
UNASSIGNED: In particular, the ARA-Net adopts a similar strategy as UNet to perform the area segmentation. Skip self-attention connection (SSA) block, comprising a shortcut and a parallel polarized self-attention (PPSA) block, has been proposed to deal with the challenges of blurred boundaries and irregular shapes of the retinal atrophic region. Further, we have proposed a multi-scale feature flow (MSFF) to challenge the size variation. We have added the flow between the SSA connection blocks, allowing for capturing considerable semantic information to detect retinal atrophy in various area sizes.
UNASSIGNED: The proposed method has been validated on the Pathological Myopia (PALM) dataset. Experimental results demonstrate that our method yields a high dice coefficient (DICE) of 84.26%, Jaccard index (JAC) of 72.80%, and F1-score of 84.57%, which outperforms other methods significantly.
UNASSIGNED: Our results have demonstrated that ARA-Net is an effective and efficient approach for retinal atrophic area segmentation in PM.

To compare the rate of retinal atrophy over time in patients with relapsing-remitting multiple sclerosis (RRMS) treated with various disease-modifying therapies (DMT).
Patients with RRMS on various DMT and those observed without treatment were prospectively enrolled into the study between September 2015 and June 2018. All subjects with follow-up of 1-4 years were included and categorized into groups as \"no drug\", \"low efficacy drug\", \"high efficacy drug\", or \"dimethyl fumarate\" (DMF), based on treatment modality used for the longest duration of their follow-up. Ocular coherence tomography (OCT) was used to measure peripapillary retinal nerve fiber layer thickness (RNFL) and ganglion cell/inner plexiform layer (GC-IPL) thickness at baseline and every 6 months. A linear mixed effects regression model was performed to compare rates of retinal atrophy across treatment groups.
Out of 67 participants who met inclusion criteria (mean age = 37; 76% female), 13 were untreated, 12 on low efficacy therapy, 18 on DMF, and 24 on high efficacy therapy. History of optic neuritis was associated with lower baseline GC-IPL thickness (p = 0.003). Higher baseline GC-IPL thickness was associated with increased rate of GC-IPL thinning (p = 0.009). Age, disease duration, and ethnicity were not predictors of baseline RNFL or GC-IPL thickness, or rate of atrophy of these layers.
There were no differences in rate of GC-IPL atrophy between patients with RRMS on different treatments in this cohort. Age, disease duration, and ethnicity also did not predict retinal atrophy. History of ON was associated with reduced GC-IPL thickness at baseline, consistent with previous research. Rate of GC-IPL thinning was higher for subjects with higher baseline GC-IPL thickness, suggesting a plateau effect.

UNASSIGNED: Aplastic anemia can cause ophthalmic abnormalities in patients. Vision loss in a child with aplastic anemia due to massive retinal hemorrhages at various levels is rare.
UNASSIGNED: A pediatric patient with aplastic anemia presented with retinal hemorrhages at multiple levels along with a serous retinal detachment in both eyes and subsequent retinal changes after pars plana vitrectomy.
UNASSIGNED: Anemia and thrombocytopenia in aplastic anemia could cause severe retinal hemorrhages and result in retinal atrophy and retinal edema. Vitrectomy can be performed to remove vitreous hemorrhage, but risk factors for retinal atrophy and edema need further investigation.

OBJECTIVE: To investigate the confounding effect of nonexudative age-related macular degeneration (AMD), specifically drusen and outer retinal atrophy, on the architecture and automated segmentation of the inner retinal layers as measured with OCT.
METHODS: Observational cross-sectional study.
METHODS: Two hundred sixty-three consecutive eyes with nonexudative AMD were identified through a retrospective chart review. Exclusion criteria were a diagnosis of glaucoma or glaucoma suspect, other retinal pathology affecting the macula, axial length > 26.5 mm or spherical equivalent less than -6 diopters, any other optic nerve or neurologic disorders, or poor image quality.
METHODS: Drusen were automatically segmented on macular OCT B-scans with a publicly available and validated deep learning approach. Automated segmentation of the inner plexiform layer (IPL)/inner nuclear layer (INL) boundary was carried out with the device\'s proprietary software.
METHODS: Quality of segmentation of the IPL/INL boundary as a function of drusen size and presence of inner retinal layer displacement in the area of macular pathology (drusen or atrophy).
RESULTS: One hundred twenty-five eyes (65 patients) met the inclusion criteria. Drusen size varied between 16 and 272 μm (mean, 118 μm). Automated segmentation had a 22% chance of failure if the drusen height was between 145 and 185 μm and was most likely to fail with drusen heights above 185 μm. When drusen height was normalized by total retinal thickness, segmentation failed 36% of the time when the drusen to total retinal thickness ratio was 0.45 or above. Images were likely to show displacement of inner retinal layers with drusen heights above 176 μm and a normalized drusen height ratio of 0.5 or higher. Eighty-seven percent of images with outer retinal atrophy displayed incorrect segmentation.
CONCLUSIONS: Outer retinal diseases can alter the retinal topography and affect the segmentation accuracy of the inner retinal layers. Large drusen may cause segmentation error and compression of the inner macular layers. Geographic atrophy confounds automated segmentation in a high proportion of eyes. Clinicians should be cognizant of the effects of outer retinal disease on the inner retinal layer measurements when interpreting the results of macular OCT imaging in patients with glaucoma.