Short-term efficacy of photobiomodulation in early and intermediate age-related macular degeneration: the PBM4AMD study.

OBJECTIVES: This independent prospective study evaluated the short-term effects and safety of photobiomodulation (PBM) in early and intermediate age-related macular degeneration. METHODS: patients were treated with PBM in one eye. Functional parameters and drusen volume were measured at one (W4), three- (W12) and six-months (W24) after PBM. RESULTS: The study included 38 subjects who completed the PBM protocol. Two patients developed macular neovascularization during the study period. Best corrected visual acuity improved from 77.82 ± 5.83 ETDRS letters at baseline to 82.44 ± 5.67 at W12 (p < 0.01), then declined to 80.05 ± 5.79 at W24 (p < 0.01 vs. baseline). Low luminance visual acuity showed a similar pattern, improving from 61.18 ± 8.58 ETDRS letters at baseline to 66.33 ± 8.55 at W12 (p < 0.01), and decreasing to 62.05 ± 9.71 at W24 (p = 0.02). Contrast sensitivity improved at W12 (20.11 ± 9.23 ETDRS letters, p < 0.01), but returned to baseline by W24 (16.45 ± 9.12, p = 0.5). Scotopic microperimetry showed a decrease in mean absolute retinal sensitivity from 9.24 ± 3.44 dB to 7.47 ± 4.41 dB at W24 (p < 0.01), while relative sensitivity decreased only at W24 (p = 0.04). Drusen volume decreased at W4 (0.018 ± 0.009 mm3, p < 0.01) and W12 (0.017 ± 0.009 mm3, p < 0.01), with a slight increase at W24 (0.019 ± 0.012 mm3, p = 0.154). CONCLUSIONS: PBM resulted in temporary improvements in visual function and a reduction in drusen volume, but these effects were not sustained at six months. The long-term efficacy and impact on disease progression are uncertain, necessitating further research to confirm these findings and determine optimal patient selection.

Ten-Year Follow-Up of Fellow Eyes in Patients with Unilateral Naïve Exudative AMD.

PURPOSE: To determine the 10-year morphological outcomes and identify potential risk factors for exudative AMD in the fellow eyes (FE) in patients with naïve exudative AMD. METHODS: Data from 100 patients were retrospectively reviewed. Baseline macular neovascularization (MNV) type in the exudative AMD eye and presence of drusen, intraretinal hyperreflective foci (iHRF), non-foveal incomplete atrophy (iRORA), central retinal thickness and subfoveal choroidal thickness in the FEs were analyzed as biomarkers for progression in the second eye. RESULTS: 54 patients developed exudative AMD in the FE at the end of the follow-up. Subjects with type 2 and 3 MNV in the exudative AMD eye had a higher risk of exudative AMD in the FE (HR=3.365; p=0.039 and HR=3.801; p=0.037). FEs with drusen (large HR=6.938, p=0.001; cuticular HR=6.937, p<0.0001; subretinal drusenoid deposits HR=13.678, p<0.0001) and iHRF (HR=1.853, p=0.041) were also at higher risk. Seven patients were legally blind by the end of the follow-up. CONCLUSIONS: The rate of exudative AMD in the FE was 54% 10 years after the diagnosis in the exudative eye. The FE of patients with type 2 and 3 MNV was at high risk for early progression. Drusen and iHRF were also significant risk factors for MNV development.

Ischemic optic neuropathy as first presentation in patient with m.3243 A > G MELAS classic mutation.

BACKGROUND: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a systemic disorder in which multi-organ dysfunction may occur from mitochondrial metabolism failure. Maternally inherited mutations in the MT-TL1 gene are the most frequent causes for this disorder. Clinical manifestations may include stroke-like episodes, epilepsy, dementia, headache and myopathy. Among these, acute visual failure, usually in association with cortical blindness, can occur because of stroke-like episodes affecting the occipital cortex or the visual pathways. Vision loss due to optic neuropathy is otherwise considered a typical manifestation of other mitochondrial diseases such as Leber hereditary optic neuropathy (LHON). CASE PRESENTATION: Here we describe a 55-year-old woman, sister of a previously described patient with MELAS harbouring the m.3243A > G (p.0, MT-TL1) mutation, with otherwise unremarkable medical history, that presented with subacute, painful visual impairment of one eye, accompanied by proximal muscular pain and headache. Over the next weeks, she developed severe and progressive vision loss limited to one eye. Ocular examination confirmed unilateral swelling of the optic nerve head; fluorescein angiography showed segmental perfusion delay in the optic disc and papillary leakage. Neuroimaging, blood and CSF examination and temporal artery biopsy ruled out neuroinflammatory disorders and giant cell arteritis (GCA). Mitochondrial sequencing analysis confirmed the m.3243A > G transition, and excluded the three most common LHON mutations, as well as the m.3376G > A LHON/MELAS overlap syndrome mutation. Based on the constellation of clinical symptoms and signs presented in our patient, including the muscular involvement, and the results of the investigations, the diagnosis of optic neuropathy as a stroke-like event affecting the optic disc was performed. L-arginine and ubidecarenone therapies were started with the aim to improve stroke-like episode symptoms and prevention. The visual defect remained stable with no further progression or outbreak of new symptoms. CONCLUSIONS: Atypical clinical presentations must be always considered in mitochondrial disorders, even in well-described phenotypes and when mutational load in peripheral tissue is low. Mitotic segregation of mitochondrial DNA (mtDNA) does not allow to know the exact degree of heteroplasmy existent within different tissue, such as retina and optic nerve. Important therapeutic implications arise from a correct diagnosis of atypical presentation of mitochondrial disorders.

Delaying anti-VEGF therapy during the COVID-19 pandemic: long-term impact on visual outcomes in patients with neovascular age-related macular degeneration.

OBJECTIVES: To evaluate the outcomes of delayed intravitreal injections (IVIs) caused by the outbreak of coronavirus disease 2019 (COVID-19), in patients with neovascular age-related macular degeneration (nAMD). METHODS: nAMD patients with scheduled IVIs between March 1st and April 30th, 2020 were stratified through a risk-based selection into a non-adherent group (NA-group) if they skipped at least one IVI and an adherent group (A-group) if they followed their treatment schedule. During the pandemic visit (v0), if a significant worsening of the disease was detected, a rescue therapy of three-monthly IVIs was performed. Multimodal imaging and best-corrected visual acuity (BCVA) findings were evaluated after 6 months (v6), compared between groups and with the visit prior the lockdown (v-1). RESULTS: Two hundred fifteen patients (132 females, mean age: 81.89 ± 5.98 years) delayed their scheduled IVI while 83 (53 females, mean age: 77.92 ± 6.06 years) adhered to their protocol. For both groups, BCVA at v0 was significantly worse than v-1 (mean 4.15 ± 7.24 ETDRS letters reduction for the NA-group and 3 ± 7.96 for the A-group) but remained stable at v6. The two groups did not significantly differ in BCVA trends after 6 months and neither for development of atrophy nor fibrosis. CONCLUSIONS: A risk-based selection strategy and a rescue therapy may limit the long-term outcomes of an interruption of the treatment protocol in patients with nAMD.

RESPONSE TO TREATMENT OF CHOROIDAL NEOVASCULARIZATION IN HIGHLY MYOPIC EYES WITH DOME-SHAPED MACULA: Two Years of Follow-Up.

PURPOSE: To compare the 2-year outcome to antivascular endothelial growth factor therapy for myopic choroidal neovascularization (CNV) in the eyes with or without dome-shaped macula (DSM). METHODS: Data from treatment-naive myopic CNV with a 2-year follow-up were retrospectively collected and divided into two groups according to the presence of DSM. The best-corrected visual acuity was acquired at baseline, 3, 12, and 24 months. The association between visual outcomes and CNV type and area, presence of scleral-derived feeder vessel, macular atrophy, and lacquer cracks at baseline was also evaluated. RESULTS: Fifty-four eyes of 54 patients were included; 18 eyes (33.4%) had DSM. Choroidal neovascularization was foveal in 10 DSM eyes (55.6%) and in 30 non-DSM eyes (83.9%), P = 0.033. At baseline, the mean best-corrected visual acuity was significantly higher in the DSM group (68.33 ± 12.04 Early Treatment Diabetic Retinopathy Study letters, 20/40 Snellen) compared with the non-DSM group (57.75 ± 13.46 Early Treatment Diabetic Retinopathy Study letters, 20/72 Snellen; P = 0.007). This difference disappeared after 3 months and did not reoccur afterward. All other parameters were not significantly associated with visual outcomes. CONCLUSION: Overall, DSM does not represent a negative prognostic factor in response to antivascular endothelial growth factor therapy in myopic CNVs after 2 years. However, in DSM eyes, CNVs tend to be extrafoveal, thus ensuring a good visual prognosis from the earliest stage of the disease.

ACUTE IDIOPATHIC MACULOPATHY: A Proposed Disease Staging Based on Multimodal Imaging.

PURPOSE: To describe the clinical course and the multimodal imaging of acute idiopathic maculopathy. METHODS: Medical records and multimodal imaging including color fundus photography, optical coherence tomography, and fundus autofluorescence were retrospectively reviewed. Recognition of the fundus autofluorescence patterns and their relationship with the disease duration, best-corrected visual acuity, and optical coherence tomography features represented the main outcome measures. RESULTS: Seventeen eyes of 16 patients (7 women; mean age 29.9 years) with a mean follow-up of 23.9 months were included. The mean best-corrected visual acuity at presentation was 0.63 ± 0.54 logarithm of the minimum angle of resolution (Snellen equivalent, 20/85). All but one patient had the best-corrected visual acuity recovery to 20/20. Four sequential patterns of fundus autofluorescence corresponding to 4 proposed stages of disease were observed. Patterns 1 (central hypoautofluorescence with surrounding hyperautofluorescence) and 2 (stippled hyperautofluorescence and hypoautofluorescence) were found at presentation. Patterns 3 (central hyperautofluorescence surrounded by hypoautofluorescence) and 4 (hypoautofluorescence) were observed during the disease course and/or at the last follow-up visit. Duration of the disease was significantly different between patterns at baseline and last visit. Pattern 1 significantly related to the presence of subretinal detachment (Fisher's exact test; P =0.003) on optical coherence tomography in comparison with Pattern 2. Pattern 4 showed unique homogeneously decreased autofluorescence with corresponding attenuation of retinal pigment epithelium and restored outer retinal layers on optical coherence tomography. CONCLUSION: A sequential disease staging based on multimodal imaging for acute idiopathic maculopathy is proposed. The recognition of the observed imaging patterns may help clinicians in the correct diagnosis and patient counseling.

Evidence of retinal anterograde neurodegeneration in the very early stages of multiple sclerosis: a longitudinal OCT study.

BACKGROUND: Neurodegenerative processes are present since the early stages of multiple sclerosis (MS), constituting the primary substrate of disability. As part of the CNS, retinal damage could be considered a reliable prognostic biomarker of neurodegeneration in MS. OBJECTIVES: To characterize longitudinal changes in the retinal layers' thickness and to investigate correlations between retinal atrophy and other prognostic biomarkers, i.e., cerebrospinal fluid (CSF) ß-amyloid1-42 (Aß) levels. METHODS: Forty-two eyes without a history of optic neuritis of 23 MS patients were recruited. All patients underwent spectral-domain-OCT scans (SD-OCT), brain magnetic resonance imaging (MRI), and lumbar puncture at baseline. SD-OCT and brain MRI were repeated after 12 months. Ten controls underwent the same OCT procedure. RESULTS: At baseline, macular ganglion cell/inner plexiform layer (mGCIPL) thickness was reduced in patients compared to controls (p = 0.008), without retinal nerve fiber layer (RNFL) thinning, that was revealed only at follow-up (p = 0.005). Patients with lower CSF Aß levels displayed reduced RNFL thickness values, both at baseline and follow-up. CONCLUSIONS: At very early clinical stages, mGCIPL thickness values were reduced without a concomitant peripapillary RNFL thinning. The longitudinal assessment demonstrated a RNFL loss in patients compared to HC, together with a plateau of mGCIPL thinning. Aßlow subgroup of patients showed a reduction of retinal nerve fiber layer thickness.

The loss of macular ganglion cells begins from the early stages of disease and correlates with brain atrophy in multiple sclerosis patients.

BACKGROUND: The importance of neurodegeneration in multiple sclerosis (MS) is increasingly well recognized. OBJECTIVES: To evaluate retinal pathology using optical coherence tomography (OCT) and to investigate possible associations between retinal layers' thickness and specific patterns of gray matter volume in patients with a new diagnosis of MS. METHODS: A total of 31 patients underwent OCT scans and brain magnetic resonance imaging. In total, 30 controls underwent the same OCT procedure. The association between focal cortical volume and OCT measurements was investigated with voxel-based morphometry (VBM). RESULTS: Compared to controls, patients' macular retinal nerve fiber layer (mRNFL), macular ganglion cell layer (mGCL), macular inner plexiform layer (mIPL), and macular ganglion cell-inner plexiform layer (mGCIPL) thickness were significantly reduced ( p = 0.0009, p = 0.0003, p = 0.0049, and p = 0.0007, respectively). Peripapillary RNFL (pRNFL) and temporal sector pRNFL (T-pRNFL) did not show any significant changes, although there was a trend toward T-pRNFL thinning ( p = 0.0254). VBM analysis showed that mGCIPL and pRNFL were significantly correlated with the volume reduction of occipital-parietal cortex ( p < 0.005). CONCLUSION: mRNFL, mGCL, and mIPL are significantly reduced in MS patients without concomitant pRNFL thinning. These retinal changes show a significant association with cortical regions that are known to be important for visuospatial performance.