Bilateral Acute Macular Neuroretinopathy (AMN) after COVID-19 and its Clinical Course. / Bilaterale akute makuläre Neuroretinopathie (AMN) nach COVID-19 und Verlauf.

Acute macular neuroretinopathy (AMN) is a rare disease entity. It is mainly observed in young women with a history of influenza-like infection or who have been taking oral contraceptives for several years. Patients typically describe subjective visual deterioration and mono- or bilateral paracentral relative scotomas. In some cases, funduscopic ophthalmic examination may reveal subtle sharply demarcated flat lesions of reddish-brown or orange colour in the macular region. Diagnosis is usually made by near-infrared fundus imaging which shows hyporeflective areas, and SD-OCT imaging which manifests changes in the outer retinal layers. In the following, three patient cases with bilateral AMN are described which occurred in direct temporal relationship to a recent SARS-CoV-2 infection.

[Acute macular neuroretinopathy: a case report].

A 16-year-old female patient experienced a rapid decline in bilateral visual acuity accompanied by central scotomas for 5 days following coronavirus disease 2019 infection. Ocular examination revealed findings consistent with acute macular neuroretinopathy. Structural en face imaging using optical coherence tomography demonstrated a wedge-shaped lesion with low reflectivity directed towards the fovea in both eyes. B-scan images revealed localized hyperreflective bands involving the outer nuclear layer and photoreceptor layer, with discontinuity of the ellipsoid zone. Based on clinical presentation and examination findings, a diagnosis of bilateral acute macular neuroretinopathy was established.

INTERNAL LIMITING MEMBRANE PEELING DISTORTS THE RETINAL LAYERS AND INDUCES SCOTOMA FORMATION IN THE PERIFOVEAL TEMPORAL MACULA.

PURPOSE: To determine whether internal limiting membrane peeling damages retinal function in patients with an idiopathic macular hole. METHODS: Retrospective case series. Forty-five eyes of 45 idiopathic macular hole patients who underwent vitrectomy with internal limiting membrane peeling with a minimum follow-up of 6 months. Each patient received a complete ophthalmological examination. The eyes were examined by microperimetry MP-3 in the central 20° visual field and optical coherence tomography angiography in the central 6 × 6 mm area. RESULTS: Six months after the surgery, macular hole closed in each patient. Retinal sensitivity decreased significantly in the perifoveal temporal ETDRS sector (from 24.97 ± 2.67-19.98 ± 5.68 dB, P = 0.001) but not in the other sectors. Six patients (13%) developed 24 scotomas, 62.5% presented in the perifoveal temporal sector. Anatomically, bumps in the outer nuclear layer were discovered concurrent with inner retinal dimples on B-scan images, predominantly (76.8%) in the perifoveal temporal sector, which have not been previously reported. The incidence of outer nuclear layer bumps was significantly higher in patients with scotomas than in those without (83% vs. 18%, P = 0.014). CONCLUSION: Internal limiting membrane peeling induced functional changes specifically in the perifoveal temporal macula. Distortion in the retinal layers is proposed to underly scotomas pathogenesis.

Highly accurate retinotopic maps of the physiological blind spot in human visual cortex.

The physiological blind spot is a naturally occurring scotoma corresponding with the optic disc in the retina of each eye. Even during monocular viewing, observers are usually oblivious to the scotoma, in part because the visual system extrapolates information from the surrounding area. Unfortunately, studying this visual field region with neuroimaging has proven difficult, as it occupies only a small part of retinotopic cortex. Here, we used functional magnetic resonance imaging and a novel data-driven method for mapping the retinotopic organization in and around the blind spot representation in V1. Our approach allowed for highly accurate reconstructions of the extent of an observer's blind spot, and out-performed conventional model-based analyses. This method opens exciting opportunities to study the plasticity of receptive fields after visual field loss, and our data add to evidence suggesting that the neural circuitry responsible for impressions of perceptual completion across the physiological blind spot most likely involves regions of extrastriate cortex-beyond V1.

Case series of photic maculopathy associated with exposure to a plasma flash induced by a femtosecond laser.

BACKGROUND AND OBJECTIVES: Photic maculopathy resulting from laser-induced plasma flash has been rarely reported, and the corresponding mechanism of the injury is still unclear. We present a case series of three patients with bilateral macular injuries produced by exposure to the plasma radiation from femtosecond laser tightly focusing. STUDY DESIGN/MATERIALS AND METHODS: Funduscopic findings were accompanied mainly by optical coherence tomography (OCT) investigation of the macula during the follow-up period. RESULTS: All patients shared similar clinical symptoms soon after the initial injury, including reduced visual acuity and central scotomas. It was acutely characterized by foveolar yellowish faceted lesions upon fundus examination. The main OCT finding in the acute stage was a hyper-reflective area involving all foveolar retinal layers without retinal edema. Repeat OCT evaluation during the latter stages revealed that the retinal changes were reversible, but delineated mild pathology at the outer foveal retina. This retinal structural recovery was accompanied by improvements in visual acuity and central scotomas as well. CONCLUSIONS: Prolonged viewing of a plasma flash induced by a focused femtosecond laser without eye protection may produce persistent damage to the retina. We believe that a photochemical process similar to the mechanism of a solar burn or welder's maculopathy may cause retinal damage in this case series.

Investigation of progression pattern and associated risk factors in glaucoma patients with initial paracentral scotomas using Humphrey 10-2.

Central visual field (VF) progression could directly threaten patientss visual function compared to glaucomatous damage. This study was designed to investigate visual field (VF) progression pattern and associated risk factors including optical coherence topography angiographic (OCT-A) findings in glaucoma patients with initial paracentral scotoma. This prospective, observational study included 122 eyes presenting as initial paracentral scotomas with serial 24-2 and 10-2 VF tests at the glaucoma clinic of Seoul St Mary's Hospital between November 2017 and August 2020. The participants underwent at least 5 serial VF exams and OCT-A at baseline. Numerical values of the initial and final 10-2 VF tests were averaged for each VF test point using the total deviation map. Innermost 10-2 VF progression was defined as three or more new contiguous points at the central 12 points on 10-2 VF. Other clinical characteristics were collected including history of disc hemorrhage and vessel density (VD) was measured from OCT-A images. Linear regression analysis was performed to obtain the change of mean deviation and a cut-off for progression was defined for both 24-2 and 10-2 VFs. The average total deviation maps of the initial 10-2 VF tests shows initial paracentral scotoma located in the superior region in an arcuate pattern that was deep in the 4°-6° region above fixation. This arcuate pattern was more broadly located in the 4°-10° region in the primary open-angle glaucoma (POAG) group, while it was closer to fixation in 0°-4° region in the normal-tension glaucoma (NTG) group. The final average map shows deepening of scotomas in the 4°-10° region in POAG, which deepened closer to the region of fixation in NTG. The diagnosis of NTG (ß 1.892; 95% CI 1.225-2.516; P = 0.035) and lower choroidal VD in the peripapillary atrophy (PPA) region (ß 0.985; 95% CI 0.975 to 0.995; P = 0.022) were significantly related to innermost 10-2 VF progression. Initial paracentral scotomas in NTG tended to progress closer to the region of fixation, which should be monitored closely. Important progression risk factors related to paracentral scotoma near the fixation were the diagnosis of NTG and reduced choroidal VD in the ß-zone PPA region using OCT-A. We should consider vascular risk factors in NTG patients presenting with initial paracentral scotoma to avoid vision threatening progression of glaucoma.

Legionnaire's disease presenting as bilateral central scotomata: a case report.

BACKGROUND: Legionnaire's disease is one of the major causes of community-acquired pneumonia and is occasionally complicated by neurological symptoms. However, reports of ocular lesions due to Legionnaire's disease are limited. CASE PRESENTATION: We report the case of a patient with Legionnaire's disease presenting as bilateral central scotomata due to retinal lesions. The patient consulted due to fever and bilateral central scotomata, as well as other extrapulmonary symptoms. Optical coherence tomography (OCT) showed bilateral accumulations of fluid under the retina, and the patient was diagnosed with bilateral exudative retinal detachment. Later, Legionnaire's disease was confirmed by pulmonary infiltrates on chest imaging and positive urinary antigen for Legionella pneumophila. After administration of antibiotics, the bilateral central scotomata and bilateral subretinal fluid accumulations completely resolved, as did the other extrapulmonary symptoms and the pulmonary infiltrates. Thus, the bilateral central scotomata due to exudative retinal detachment were thought to be caused by Legionnaire's disease. CONCLUSIONS: This case demonstrates that Legionnaire's disease can present as bilateral central scotomata. We may consider the possibility of extrapulmonary involvement complicating Legionnaire's disease when we encounter bilateral ocular lesions in patients with fever and pneumonia.

Photopsia.

'Photopsia' describes the symptom of visual disturbances that are typically flash-like, sudden in onset and brief, and occurring without light entering the eye. Patients reporting photopsia often pose a diagnostic challenge, given the wide range of possible neurological and ophthalmological causes. We review the common causes of photopsia, discuss the assessment and workup of this symptom, and stress the importance of close interdisciplinary liaison to help with its diagnosis and management. We discuss a patient with acute zonal occult outer retinopathy to illustrate these points.

Abnormal Visual Function Outside the Area of Atrophy Defined by Short-Wavelength Fundus Autofluorescence in Stargardt Disease.

Purpose: To examine the extent of visual function abnormality outside the dark lesion on short-wavelength fundus autofluorescence (SW-AF), and its correlation with background SW-AF features and optical coherence tomography (OCT) in recessive Stargardt disease (STGD1). Methods: Forty-nine eyes of 25 participants in the ProgStar (the Natural History of the Progression of Atrophy Secondary to Stargardt Disease) study at our center were included. Patients underwent microperimetry (both threshold and dense scotoma mapping), OCT, SW-AF, and visual acuity testing. The Fisher's exact test, the χ2 test, and unpaired t-tests were used to analyze the data. Results: Of 40 eyes without central fixation, 33 (82%) placed fixation remote (most ≥5°) from the dense scotoma edge, despite good intervening retinal sensitivity. OCT findings accounted for the remote fixation in 75%. Eighteen (37%) of all 49 eyes had dense scotoma extending past the dark lesion border. OCT was not adequate to define the edge of the scotoma. Of the 49 eyes, 28 (57%) had the mottled background pattern, 10 (20%) had the uniform pattern, and 11 (22%) had the other pattern, with >75% of eyes in each pattern having remote fixation. The dense scotoma exceeded the dark lesion primarily in the mottled pattern. The two eyes of each patient were concordant in all features. Conclusions: Functional abnormalities in STGD1 extend past the SW-AF dark lesion. The disruption of the ellipsoid zone shows that photoreceptor abnormality extends peripheral to the dark lesion, and it explains in part the remote fixation pattern and the dense scotoma exceeding the dark lesion. This has implications for clinical trials for STGD1.

Patchy Scotoma Observed in Chorioretinal Patchy Atrophy of Myopic Macular Degeneration.

Purpose: To investigate the retinal sensitivity of highly myopic eyes with chorioretinal patchy atrophy (PA) using microperimetry. Methods: Fifty-two eyes of 32 patients with high myopia were prospectively included. Twenty-two eyes of 16 patients had PA lesions; eyes without PA were analyzed as controls. Testing points on microperimetry in eyes with PA were designated as 3 zones: zone 1 as the PA lesion including its borders; zone 2 including testing points adjoining PA; zone 3 including all other testing points. Results: In the PA group, the mean retinal sensitivity in zone 1 was 2.1 ± 2.8 dB, zone 2 = 8.3 ± 4.3 dB, and zone 3 = 9.4 ± 4.1 dB. Sensitivity in zone 1 was significantly reduced than zones 2 and 3 (P < 0.001). The mean retinal sensitivity in the PA group was lower than controls (6.5 ± 4.3 vs 13.9 ± 4.1 dB, P < 0.001), and combined zone 2 and 3 in the PA group also presented lower retinal sensitivity (8.8 ± 4.0 dB). Conclusions: Eyes with PA generate patchy scotoma in PA lesions and reduced retinal sensitivity in regions beyond atrophic lesion on microperimetry. The presence of PA may be an indicator to reflect both significantly anatomical and functional alterations on myopic macular degeneration.

Is "normal tension glaucoma" glaucoma?

Primary open angle glaucoma (POAG) represents a distinct disease entity with elevated intraocular pressure (IOP) as the main risk factor, even though the reasons for why the IOP is elevated remains to be elucidated. It is considered that normal tension glaucoma (NTG) is a subtype of POAG, comprising a special form of glaucomatous neurodegeneration or glaucomatous optic neuropathy (GON) almost exactly the same as that seen in POAG, but the IOP, as named, remains in the statistically normal range. Actually the disease entity of NTG has been a profound confusion and it is difficult to be accurately conceptualized. One of the reasons is that the IOP is closely linked to the occurrence of GON in POAG but not in NTG, and for the latter, it seems that GON is secondary to a number of local or systemic disorders. In recent years, increasing evidences suggest that NTG or IOP independent GON is a non-glaucomatous disease with different disease entities from POAG and with more diverse and complex etiologies. Here we hypothesized that NTG, at least for those with recognizable primary diseases, is not a glaucomatous disease; instead, it represents a group of disorders with GON as a characteristic clinical feature or phenotype.

SEQUENTIAL CHANGES IN HYDROXYCHLOROQUINE RETINOPATHY UP TO 20 YEARS AFTER STOPPING THE DRUG: Implications for Mild Versus Severe Toxicity.

PURPOSE: To characterize the stability or progression of different stages of hydroxychloroquine (HCQ) retinopathy up to 20 years after stopping the drug. METHODS: We reviewed findings from 13 patients with initial HCQ retinopathy classified as early (patchy photoreceptor damage), moderate (ring of photoreceptor thinning or scotoma), or severe (retinal pigment epithelial [RPE] damage). Patients had been off HCQ for as many as 14 years at initial examination and were subsequently followed for 5 years to 8 years with repeated fundus autofluorescence and spectral domain optical coherence tomography. RESULTS: Early and moderate cases stabilized in fundus autofluorescence appearance, foveal thickness, ellipsoid zone line length, and visual acuity for up to 9 years after stopping HCQ. By contrast, severe cases demonstrated a continual loss of these parameters for up to 20 years off the drug. The presence of RPE damage at initial examination predicted progressive retinopathy over many years. CONCLUSION: The steady progression of severe HCQ retinopathy in eyes showing RPE damage after drug cessation suggests a metabolic insult that chronically destabilizes rather than destroys cellular function, with a clinical course resembling that of genetic dystrophies. Our findings stress the importance of early detection to minimize progression and visual loss.

Autoimmune Retinopathy.

The autoimmune retinopathies (AIRs) are a group of inflammatory-mediated retinopathies that present with unexplained visual loss (both central and peripheral), visual field defects, usually a ring scotoma, photoreceptor dysfunction as evident on electroretinography (ERG), and circulating autoantibodies against retinal antigens. The fundus may be normal or may show vascular attenuation, retinal atrophy with or without pigmentary changes or waxy pallor of the optic disc, and no or minimal inflammatory cells.

Full-field ERG as a predictor of the natural course of ABCA4-associated retinal degenerations.

Purpose: To assess retinal function in combination with the retinal structure in ABCA4-associated retinal degenerations. Moreover, to evaluate the possibility of predicting the natural course of these disorders. Methods: 34 patients with Stargardt disease or cone rod dystrophy carrying confirmed mutations in ABCA4 were selected from our retinitis pigmentosa (RP) register. Sequence analysis of the entire coding region of the ABCA4 gene was performed. The patients were subdivided into three groups based on their most recent visual fields. Group 1 included ten patients with central scotomas within 10°, group 2 included 19 patients with larger central scotomas of 10-35°, and group 3 included five patients with mere temporal residues. The patients underwent slit-lamp and fundus examinations, visual acuity testing, optical coherence tomography (OCT), fundus photography (color, red-free, and autofluorescence (AF) images), full-field electroretinography (ffERG), and multifocal electroretinography (mERG). FfERG and mERG results were analyzed statistically. Total rod and cone function, as well as macular function, was compared between the three groups and of each group to a normal material. In 23 patients who had undergone ffERG on a previous occasion, the 30 Hz flicker implicit time (IT) from the first visit was also analyzed. Results: The ffERG statistics revealed significant differences between the groups regarding cone and rod function with group 1 showing the highest amplitudes and the shortest ITs while group 3 demonstrated the lowest amplitudes and the most delayed ITs. When compared to controls, group 1 did not show any significant changes while groups 2 and 3 demonstrated reduced amplitudes and delayed 30 Hz ITs. Regarding estimation of the natural course, identical results of the 30 Hz IT were encountered for the groups also at the first visit early in the course of disease. Comparison of the mERGs showed significant differences with group 1 demonstrating the highest amplitudes and group 3 the lowest for all rings but rings 2 and 3 in the right eye for which the amplitudes were the second highest. The mERGs for each group were also compared to controls showing reduced mERG amplitudes for all rings in all groups, except group 1, left eye. OCT showed macular attenuation in all patients. Evaluation of the inner and outer photoreceptor junction (IS/OS) morphology revealed alterations related to macular function measured with mERG in all eyes. Eight patients in group 1 showed foveal IS/OS junction loss, one had foveal IS/OS junction disorganization, and one had IS/OS loss also beyond the fovea. In group 2, one patient had IS/OS junction loss confined to the fovea, and the rest showed total loss of IS/OS junctions. Group 3 was devoid of IS/OS junctions. Concerning the AF images, group 1 showed small areas of absent AF in the macula, peripapillary sparing, and flecks of increased and reduced AF in the posterior pole. In group 2, the central areas of absent AF were larger. Flecks of reduced AF were the most dominant and reached beyond the posterior pole. Seven of 19 patients had peripapillary sparing. In group 3, large confluent areas of reduced AF were found in the posterior pole and beyond with small areas of increased AF in the far periphery. No peripapillary sparing was seen. Conclusions: The current study demonstrates a significant difference in total retinal function, as well as macular function, between patients with ABCA4-associated retinal degeneration and a different degree of visual field defects with gradual deterioration of function along with increased visual field constriction. Likewise, the morphological changes, including the deviant AF pattern and loss of IS/OS junctions, that were related to macular function measured with mERG worsened with the degree of visual field defects. Moreover, in these groups of patients with ABCA4-associated retinal degenerations, full-field cone 30 Hz flicker IT seems to be a predictor of the natural course of the disease also on long-term follow-up.

MICROPERIMETRY IN BEST VITELLIFORM MACULAR DYSTROPHY.

PURPOSE: To investigate retinal sensitivity in eyes with all the clinical stages of Best vitelliform macular dystrophy (VMD). METHODS: Thirty-two patients affected by VMD in subclinical, vitelliform, pseudohypopyon, vitelliruptive, and atrophic stages were enrolled in this prospective cross-sectional study. Patients underwent a complete ophthalmologic examination, including determination of best-corrected visual acuity (BCVA), staging of the disease (Gass's classification), and microperimetry by means of the macular integrity assessment microperimeter. The primary outcome measure was to describe the alterations in the retinal sensitivity of eyes affected by VMD in different stages. Secondary outcome measures included correlations between retinal sensitivity and best-corrected visual acuity and the correlation between the VMD stage and the specific microperimetry pattern. RESULTS: Mean retinal sensitivity was reduced in all the VMD stages. Nevertheless, vitelliform, pseudohypopyon, and vitelliruptive stages turned out to be very similar, especially within 10°. Fixation was classified as stable in 27 eyes (44.2%), relatively unstable in 16 eyes (26.2%), and unstable in 18 eyes (29.5%). Fixation stability correlated both with the disease stage and best-corrected visual acuity. CONCLUSION: VMD is characterized by complex microperimetric abnormalities, involving the whole macular area. Microperimetry may contribute to the global clinical assessment of patients affected by VMD and could be used in future therapeutic approaches.