Functional Changes of Retinal Ganglion Cells and Visual Pathways in Patients with Chronic Leber's Hereditary Optic Neuropathy during One Year of Follow-up.

Purpose: To assess changes of retinal ganglion cells (RGCs) and visual pathways' function in patients with Leber's hereditary optic neuropathy (LHON) during 12 months of follow-up of the chronic phase. Design: Retrospective case series. Participants: Twenty-two patients with LHON (mean age, 36.3±9.3 years) in the "chronic phase" of the disease, providing 42 eyes (LHON group) with different pathogenic mitochondrial DNA mutations (group 11778: 21 eyes; group 3460: 4 eyes; group 14484: 13 eyes; and group 14568: 4 eyes) were enrolled. Twenty-five age-similar healthy participants, providing 25 eyes, served as controls. Methods: Pattern electroretinogram (PERG) and visual evoked potentials (VEP), in response to 60ʹ and 15ʹ checks visual stimuli, were recorded at baseline in all subjects and after 6 and 12 months of follow-up in patients with LHON. At baseline, in all LHON eyes for each PERG and VEP parameter (amplitude and implicit time), the 95% confidence limit (CL) of test–retest variability was calculated. The PERG and VEP mean values observed in LHON eyes were compared (1-way analysis of variance [ANOVA]) with those of controls. During the follow-up, the PERG and VEP differences observed with respect to baseline were evaluated by ANOVA. Main Outcome Measures: Changes of individual and mean absolute values of 60ʹ and 15ʹ PERG amplitude and VEP amplitude and implicit time at each time point compared with baseline values in the LHON group. Results: At baseline, mean values of PERG and VEP parameters detected in the LHON group were significantly (P 0.01) different from baseline values. Conclusions: In our untreated patients with chronic LHON, with different specific pathogenic mutations, RGCs and visual pathways function were not significantly modified during 12 months of follow-up. This should be considered in the disease natural history when attempts for treatments are proposed in chronic LHON

Macular Impairment in Fabry Disease: A Morpho-functional Assessment by Swept-Source OCT Angiography and Focal Electroretinography.

Purpose Fabry disease (FD) is a multiorgan X-linked condition characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in a progressive intralysosomal deposit of globotriaosylceramide. The aim of this study was to evaluate the macular ultrastructure of the vascular network using optical coherence tomography angiography (OCTA) and to evaluate macular function using focal electroretinography (fERG) in Fabry patients (FPs). Methods A total of 20 FPs (38 eyes, mean age 57 ± 2.12 SD, range of 27-80 years) and 17 healthy controls (27 eyes, mean age 45 years ± 20.50 SD, range of 24-65 years) were enrolled in the study. Color fundus photography, swept-source optical coherence tomography (SS-OCT), OCTA and fERG were performed in all subjects. The OCTA foveal avascular zone (FAZ), vasculature structure, superficial and deep retinal plexus densities (images of 4.5 × 4.5 mm) and fERG amplitudes were measured. Group differences were statistically assessed by Student's t-test and ANOVA. Results In the FP group, the FAZ areas of the superficial and deep plexuses were enlarged (P = 0.036, t = 2.138; P < 0.001, t = -3.889, respectively), the vessel density was increased in the superficial plexus, and the fERG amplitude was reduced (P < 0.001, t = -10.647) compared with those in healthy controls. No significant correlations were found between the structural and functional data. Conclusions OCTA vascular abnormalities and reduced fERG amplitudes indicate subclinical signs of microangiopathy with early retinal dysfunction in FPs. This study highlights the relevance of OCTA imaging analysis in the identification of abnormal macular vasculature as an ocular hallmark of FD

Middle-Inner Macular Layers Dysfunction in a Case of Stellate Foveomacular Retinoschisis Detected by Abnormal Multifocal Photopic Negative Response Recordings

We describe the macular morpho-functional assessment of a 65-year-old man affected by stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR), studied by visual field, SD-OCT, autofluorescence, full-field electroretinogram (ffERG), multifocal electroretinogram (mfERG) and multifocal Photopic Negative Response (mfPhNR) recordings. The typical presentation consists of the foveal appearance of radial cartwheel pattern for the splitting of the retinal layers at the level of the Henle fiber layer (HFL) and the outer plexiform layer (OPL), perfectly seen by Spectral Domain-Optical Coherence Tomography (SD-OCT). Despite a normal function of the outer retina of the peripheral and central retina evaluated by ffERG and mfERG respectively, we observed a reduced function of the retinal elements involved in the retinoschisis by recording mfPhNR that assesses mainly inner retina function (retinal ganglion cells and their axons). Therefore, it is likely that the observed impaired mfPhNR responses reflect the signaling defects derived from the delaminated middle retina and transmitted to the innermost retinal layers

Morphological Outer Retina Findings in Multiple Sclerosis Patients With or Without Optic Neuritis

Purpose: To investigate on the morphology of the macular inner (IR) and outer (OR) layers in multiple sclerosis (MS) patients with and without history of optic neuritis (ON), followed by good or poor recovery of best corrected visual acuity (BCVA). Methods: Thirty-five normal control subjects and 93 relapsing remitting MS patients were enrolled. Of this, 40 MS patients without ON (MS-noON, 40 eyes), 27 with history of ON and good BCVA recovery (MS-ON-G, 27 eyes), and 26 with history of ON and poor BCVA recovery (MS-ON-P, 26 eyes) were studied. Controls and MS patients underwent an extensive ophthalmological examination including spectral-domain optical coherence tomography evaluating in 3 localized macular areas (0-1 mm, Area 1; 1-3 mm, Area 2; 3- 6 mm, Area 3), volumes (MV), and thicknesses (MT) of the whole retina (WR), further segmented in IR and OR. The differences of MV and MT between the groups were tested by ANOVA. In the MS-ON-P group, the correlations between MV and MT and BCVA were evaluated by Pearson's test. Results: When compared to controls, the MS-noON group showed not significantly (p &gt; 0.01) different MVs, whereas MTs were significantly (p &lt; 0.01) reduced in the evaluation of WR and IR. In the MS-ON-G group, a significant (p &lt; 0.01) reduction of WR and IR MVs and MTs was found in Areas 2 and 3; OR MVs and MTs were similar (p &gt; 0.01) to controls. In the MS-ON-P group a significant (p &lt; 0.01) reduction of WR, IR, and OR MVs and MTs was detected in all areas; the BCVA reduction was significantly (p &lt; 0.01) correlated with WR and IR MVs and MTs. Conclusions: In MS without history of ON or when ON is followed by a good BCVA recovery, the neurodegenerative process is limited to IR macular layers; in the presence of ON, with a poor BCVA recovery, a morphological impairment of both IR and OR macular layers occurs

Macular Morpho-Functional and Visual Pathways Functional Assessment in Patients with Spinocerebellar Type 1 Ataxia with or without Neurological Signs

Spinocerebellar ataxia type 1 (SCA-ATXN1) is an autosomal dominant, neurodegenerative disease, caused by CAG repeat expansion in the ataxin-1 gene (ATXN1). In isolated reports of patients with neurological signs [symptomatic patients (SP)], macular abnormalities have been described. However, no reports exist about macular anomalies in SCA1 subjects carrying the ATXN1 mutation without neurological signs [not symptomatic carriers (NSC)]. Therefore, the main aim of our work was to evaluate whether the macular functional and morphological abnormalities could be detectable in SP, genetically confirmed and with neurological signs, as well as in SCA-ATXN1-NSC, harboring pathogenic CAG expansion in ATXN1. In addition, we investigated whether the macular involvement could be associated or not to an impairment of RGCs and of their fibers and of the neural conduction along the visual pathways. Herein, nine SCA-ATXN1 subjects (6 SP and 3 NSC) underwent the following examinations: visual acuity and chromatic test assessments, fundus oculi (FO) examination, macular and peripapillary retinal nerve fiber layer thickness (RNFL-T) analysis by Spectral domain-Optical Coherence Tomography (Sd-OCT) acquisition, multifocal electroretinogram (mfERG), pattern reversal electroretinogram (PERG) and visual evoked potentials (VEP) recordings. In four eyes of two SP, visual acuity reduction and chromatic abnormalities were observed; in three of them FO changes associated with macular thinning and outer retinal defects were also detected. In three NSC eyes, slight FO abnormalities were associated with qualitative macular morphological changes. By contrast, abnormal mfERG responses (exclusively from foveal and parafoveal areas) were detected in all SP and NSC (18 eyes). No abnormalities of PERG values, RNFL-T, and VEP responses were found, but in one SP, presenting abnormal papillo-macular bundle neural conduction. Results from our SCA-ATXN1 cohort suggest that a macular dysfunction, detectable by mfERG recordings, may occur in the overt disorder, and unexpectedly in the stage of the disease in which there is still an absence of neurological signs. In NSC, an exclusive dysfunction of preganglionic macular elements can be observed, and this is associated with both normal RGCs function and neural conduction along the visual pathways

Multimodal Study of PRPH2 Gene-Related Retinal Phenotypes

PRPH2 gene mutations are frequently found in inherited retinal dystrophies (IRD) and are associated with a wide spectrum of clinical phenotypes. We studied 28 subjects affected by IRD carrying pathogenic PRPH2 mutations, belonging to 11 unrelated families. Functional tests (best-corrected visual acuity measurement, chromatic test, visual field, full-field, 30 Hz flicker, and multifocal electroretinogram), morphological retino-choroidal imaging (optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence), and clinical data were collected and analyzed. Common primary complaints, with onset in their 40s, were visual acuity reduction and abnormal dark adaptation. Visual acuity ranged from light perception to 20/20 Snellen. Visual field peripheral constriction and central scotoma were found. Chromatic sense was reduced in one third of patients. Electrophysiological tests were abnormal in most of the patients. Choroidal neovascular lesions were detected in five patients. Three novel PRPH2 variants were found in four different families. Based on the present multimodal study, we identified seven distinct PRPH2 phenotypes in 11 unrelated families carrying either different mutations or the same mutation, both within the same family or among them. Fundus autofluorescence modality turned out to be the most adequate imaging method for early recognition of this dystrophy, and the optical coherence tomography angiography was highly informative to promptly detect choroidal neovascularization, even in the presence of the extensive chorioretinal atrophy phenotype

Morpho-Functional Macular Assessment in a Case of Facioscapulohumeral Muscular Dystrophy: Photoreceptor Degeneration as Possible Cause for Reduced Visual Acuity over Three Years of Follow-Up

Background: Autosomal-dominant facioscapulohumeral muscular dystrophy (FSHD) is a muscular dystrophy with associated retinal abnormalities such as retinal vessel tortuosity, focal retinal pigment epithelium defect and large telangiectasia vessels. Methods: Case report of an FSHD 16-year-old female referred for blurred vision in both eyes (20/40), evening fever and shoulder muscle weakness over the past month preceding assessment. A multimodal assessment including visual acuity (VA), microperimetry (MP), multifocal electroretinogram (mfERG), optical coherence tomography (OCT), fluorescein angiography (FA) and fundus autofluorescence (FAF) was performed. Results: OCT showed pseudocyst macular abnormalities and disruption of the photoreceptor layer with no signs of macular ischemia/exudation. Macular function showed foveal impairment recorded by mfERG and MP as a reduction of the response amplitude density and retinal sensitivity, respectively. No medical treatment was prescribed. After three years, patient’s VA slightly improved to 20/32. OCT showed resolution of bilateral pseudocyst macular changes and persistence of photoreceptor disruption. By contrast, mfERG recordings remained abnormal for impaired foveal function and microperimetry mean sensitivity was reduced as well. Conclusions: This multimodal assessment showed persistent VA impairment at three years follow-up associated to abnormal foveal function and reduced retinal sensitivity, with spontaneous resolution of morphological macular changes, suggesting a retinal neurodegenerative process on the basis of the disease