Canine Multifocal Retinopathy in the Australian Shepherd: A Case Report

A 1-year-old Australian Shepherd (AS) was presented for a routine hereditary eye examination. During the examination multiple raised, brown to orange lesions were noted in the fundus, which could not be attributed to a known retinal disease in this breed. As they clinically most closely resembled canine multifocal retinopathy (cmr) and no indication of an acquired condition was found, genetic tests for BEST1 gene mutations were performed. These showed the dog to be homozygous for the cmr1 (C73T/R25X) gene defect. Furthermore, ultrasound (US), electroretinography (ERG), and optical coherence tomography were performed, confirming changes typical for cmr. Subsequently, the AS pedigree members were genetically and clinically tested, demonstrating autosomal recessive inheritance with no clinical symptoms in carrier animals, as was previously described for cmr. To our knowledge, this is the first reported case of canine multifocal retinopathy in the AS breed. Further investigations are under way

Erlanger Glaucoma Registry: Effect of a Long-Term Therapy with Statins and Acetyl Salicylic Acid on Glaucoma Conversion and Progression

Glaucoma disease shows a multifactorial pathogenesis, with increased intraocular pressure being the main risk factor. As retinal microcirculation was observed to be impaired in glaucoma, the improvement of capillary blood flow might be an additive option for adjuvant glaucoma therapy. The data of the present study showed that systemic drugs with cardiovascular protective properties (statins, acetylsalicylic acid (ASS)) were observed to have a trend or even significant effect on lowering glaucoma conversion and progression with a time-dependent efficiency. Thus, patients with ocular hypertension and early glaucoma seem to benefit from adjuvant cardiovascular protective therapy, yet potential side effects of systemic therapy with statins and/or ASS should be kept in mind. Thus, a thorough risk–benefit evaluation has to be performed for each patient individually. Purpose: Drugs with cardiovascular protective properties (statins, acetylsalicylic acid (ASS)) were assumed to have positive effects on patients suffering from glaucoma disease. The present retrospective study aimed to investigate the influence of statins, ASS or a combination of both on the glaucoma conversion and progression rate in glaucoma suspects and glaucoma patients with a 20-year follow-up period. Methods: A retrospective analysis of 199 eyes of 120 patients (63 male, 57 female) of the Erlanger Glaucoma Registry (EGR; ClinicalTrials.gov Identifier: NCT00494923; ISSN 2191-5008, CS-2011) was performed considering systemic therapy with statins, ASS or a combination of both: 107 eyes with ocular hypertension (OHT) and 92 eyes with pre-perimetric primary open-angle glaucoma (pre-POAG). All patients received an ophthalmological examination including morphometric and functional glaucoma diagnostics. Glaucoma conversion was defined as the conversion of OHT to pre-POAG. Glaucoma progression was defined as confirmed visual field loss. Data were shown as percentages. Statistical analysis was performed by Chi-Quadrat tests. Results: 1. Glaucoma conversion/progression was observed in 46.7% of the subjects, additionally in combination with hypercholesterinemia in 76.8%. 2. Statins: 27.3% of eyes under systemic statin therapy showed a conversion/progression. Patients taking statins ≥ 10 years yielded a reduced conversion/progression rate (p = 0.028, non-significant after Bonferroni–Holm). 3. ASS: 34.7% of eyes under systemic ASS therapy showed a conversion/progression. A significantly lower conversion/progression rate was observed after ASS therapy ≥ 12 years (p = 0.017, significant after Bonferroni–Holm). 4. ASS and statins: 25.0% of eyes under combined therapy showed a conversion/progression. A significantly reduced conversion/progression rate was reached after 8 years of combined therapy (p = 0.049, non-significant after Bonferroni–Holm). Conclusions: Patients with ocular hypertension and early glaucoma seem to benefit from adjuvant cardiovascular protective therapy. However, the benefits and disadvantages of treatment with statins and/or ASS should be kept in mind. Thus, a thorough risk–benefit evaluation has to be performed for each patient individually to avoid unwanted side effects

Extended Ganglion Cell Layer Thickness Deviation Maps With OCT in Glaucoma Diagnosis

Purpose: The aim of the present study was to investigate the diagnostic power of RGCL in the macula quantitatively and qualitatively by using a conventional and extended elliptic grid with deviation maps. Subjects and Methods: Thickness of RGCL was measured using SPECTRALIS® OCT (Heidelberg Engineering, Heidelberg, Germany) in 150 eyes of 150 subjects of the Erlangen Glaucoma Registry (EGR; NTC00494923): 26 ocular hypertension (OHT), 39 pre-perimetric open-angle glaucoma (pre-OAG), 19 normal tension glaucoma (NTG), 34 primary open-angle glaucoma (POAG), 16 secondary open-angle glaucoma (SOAG), and 16 controls. Analysis of RGCL was done quantitatively (global value, GV) and qualitatively (qualitative total value, QTV) by using a color-coded point score for data of the common elliptic macular grid of deviation maps. Furthermore, qualitative analysis of RGCL was done for an extended elliptic macula grid (extended qualitative total value, eQTV). Receiver operating characteristic (ROC) curves were calculated for the conventional and the enlarged macular grid for all subjects' groups. Results: GV of RGCL thickness differed significantly between pre-OAG (p 0.05) and controls, respectively. Quantitative ROC analysis of GV showed AUC of 0.965 (SOAG), 0.942 (POAG), 0.916 (NTG), 0.772 (pre-OAG), and 0.526 (OHT). QTV differed significantly between pre-POAG (p 0.05) and controls, respectively. Qualitative ROC analysis of QTV showed AUCs of 0.908 (NTG) 0.914 (POAG), 0.930 (SOAG), 0.734 (pre-POAG), and 0.519 (OHT). Implementation of eQTV yielded even higher AUCs for NTG (0.919), POAG (0.969), and SOAG (0.973) compared to GV. Similar AUCs of eQTV and GV were observed for OHT (0.514) and pre-OAG (0.770). Conclusion: The results of the present study showed that quantitative and qualitative analysis of RGCL thickness yielded similar diagnostic impacts compared to RNFL. Qualitative analysis might be a quick and easy useable tool for clinical all-day life. The present data suggest that analysis of an extended macula region might improve its diagnostic impact

Factors Influencing Optical Coherence Tomography Peripapillary Choroidal Thickness: A Multicenter Study.

Purpose:To quantify peripapillary choroidal thickness (PCT) and the factors that influence it in healthy participants who represent the racial and ethnic composition of the U.S. population. Methods:A total of 362 healthy participants underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head with a 24 radial B-scan pattern aligned to the fovea to Bruch's membrane opening axis. Bruch's membrane, anterior scleral canal opening (ASCO), and the anterior scleral surface were manually segmented. PCT was measured at 100, 300, 500, 700, 900, and 1100 μm from the ASCO globally and within 12 clock-hour sectors. The effects of age, axial length, intraocular pressure, ethnicity, sex, sector, and ASCO area on PCT were assessed by ANOVA and univariable and multivariable regressions. Results:Globally, PCT was thicker further from the ASCO border and thinner with older age, longer axial length, larger ASCO area, European descent, and female sex. Among these effectors, age and axial length explained the greatest proportion of variance. The rate of age-related decline increased further from the ASCO border. Sectorally, the inferior-temporal sectors were thinnest (10.7%-20.0% thinner than the thickest sector) and demonstrated a higher rate of age-related loss (from 15.6% to 20.7% faster) at each ASCO distance. Conclusions:In healthy eyes, PCT was thinnest in the inferior temporal sectors and thinner PCT was associated with older age, European descent, longer axial length, larger ASCO area, and female sex. Among these associations, age had the strongest influence, and its effect was greatest within the inferior temporal sectors

Glaucoma and Alzheimer: Neurodegenerative disorders show an adrenergic dysbalance

Glaucoma disease is characterized by an increased intraocular pressure (IOP), glaucomatous alterations of the optic disc and corresponding visual field defects. Even lowering the main risk factor IOP until an individual target level does not prevent this neurodegenerative disorder from proceeding. Several autoimmune mechanisms were discovered, partly showing a functionality. One of these autoimmune phenomena targets the ß2-adrenergic receptor (ß2-AR; i.e. agonistic autoantibodies; ß2-agAAb) and is linked to an elevated IOP and an impaired retinal microcirculation. As neurodegenerative disorder, Alzheimer’s Disease (AD) is postulated to share a common molecular mechanism with glaucoma. In the present study we investigated autoimmune phenomena targeting the ß2-AR in patients with AD. Sera of the patients were analyzed in a rat cardiomyocyte bioassay for the presence of functional autoantibodies against ß2-AR. In addition, different species of amyloid beta (Aß) monomers were tested (Aß1-14, Aß10-25, Aβ10–37 Aß1-40, Aß1-42, Aβ28–40, and Aß-[Pyr]3–43). Our results demonstrate that none of the short-chain Aß (Aß1-14, Aß10-25, or Aβ28–40) showed any agonistic or inhibitory effect on ß2-AR. Contrary, long-chain Aß-[Pyr]3–43, representing a major neurogenic plaque component, exerted an activation that after blocking by the ß2-AR antagonist ICI118.551, could be identified as that the effect was realized via the ß2-AR. Moreover, the long chain Aß1-40, Aβ1–42, and Aβ10–37, yet not the short-chain Aß peptides prevented the clenbuterol induced desensitization of the ß2-AR. In addition, we identified functional autoantibodies in the sera of AD patients, activating the ß2-AR, like the ß2-agAAb found in patients with glaucoma. As autoimmune mechanisms were reportedly involved in the pathogenesis of glaucoma and Alzheimer’s Disease, we postulate that overstimulation of the ß2-AR pathway can induce an adrenergic overdrive, that may play an important role in the multifactorial interplay of neurodegenerative disorders

Association of the retinal vasculature, intrathecal immunity, and disability in multiple sclerosis

BackgroundOptical coherence tomography angiography (OCT-A) is a novel technique allowing non-invasive assessment of the retinal vasculature. During relapsing remitting multiple sclerosis (RRMS), retinal vessel loss occurs in eyes suffering from acute optic neuritis and recent data suggest that retinal vessel loss might also be evident in non-affected eyes. We investigated whether alterations of the retinal vasculature are linked to the intrathecal immunity and whether they allow prognostication of the future disease course. Material and methodsThis study includes two different patient cohorts recruited at a tertiary German academic multiple sclerosis center between 2018 and 2020 and a cohort of 40 healthy controls. A total of 90 patients with RRMS undergoing lumbar puncture and OCT-A analysis were enrolled into a cross-sectional cohort study to search for associations between the retinal vasculature and the intrathecal immune compartment. We recruited another 86 RRMS patients into a prospective observational cohort study who underwent clinical examination, OCT-A and cerebral magnetic resonance imaging at baseline and during annual follow-up visits to clarify whether alterations of the retinal vessels are linked to RRMS disease activity. Eyes with a history of optic neuritis were excluded from the analysis. ResultsRarefication of the superficial vascular complex occured during RRMS and was linked to higher frequencies of activated B cells and higher levels of the pro-inflammatory cytokines interferon-gamma, tumor necrosis factor alpha and interleukin-17 in the cerebrospinal fluid. During a median follow-up of 23 (interquartile range 14 - 25) months, vessel loss within the superficial (hazard ratio [HR] 1.6 for a 1%-point decrease in vessel density, p=0.01) and deep vascular complex (HR 1.6 for a 1%-point decrease, p=0.05) was associated with future disability worsening. DiscussionOptic neuritis independent rarefication of the retinal vasculature might be linked to neuroinflammatory processes during RRMS and might predict a worse disease course. Thus, OCT-A might be a novel biomarker to monitor disease activity and predict future disability

Autoantibodies Activating the β2-Adrenergic Receptor Characterize Patients With Primary and Secondary Glaucoma

Recently, agonistic autoantibodies (agAAb) activating the β2-adrenergic receptor were detected in primary open-angle glaucoma (POAG) or ocular hypertension (OHT) patients and were linked to intraocular pressure (IOP) (1). The aim of the present study was to quantify β2-agAAb in the sera of glaucoma suspects and patients with primary and secondary glaucoma. Patients with OHT (n = 33), pre-perimetric POAG (pre-POAG; n = 11), POAG (n = 28), and 11 secondary OAG (SOAG) underwent ophthalmological examinations including examinations with Octopus G1 perimetry and morphometry. Twenty-five healthy individuals served as controls. Serum-derived IgG samples were analyzed for β2-agAAb using a functional bioassay. The beat-rate-increase of spontaneously beating cultured neonatal rat cardiomyocytes was monitored with 1.6 beats/15 s as cut-off. None of the sera of normal subjects showed β2-agAAb. In POAG or OHT patients increased beating rates of 4.1 ± 2.2 beats/15 s, and 3.7 ± 2.8 beats/15 s were detected (p > 0.05). Glaucoma patients with (POAG) and without perimetric (pre-POAG) defects did not differ (pre-POAG 4.4 ± 2.6 beats/15 s, POAG 4.1 ± 2.0 beats/15 s, p > 0.05). Patients with SOAG yielded mean beating rates of 4.7 ± 1.7 beats/15 s (p > 0.05). β2-agAAb were seen in 73% of OHT, 82% of pre-POAG, 82% of POAG, and 91% SOAG patients (p 0.05). The robust β2-agAAb seropositivity in patients with OHT, pre-POAG, POAG, and SOAG suggest a primary common role for β2-agAAb starting early in glaucoma pathophysiology and turned out to be a novel marker identifying all patients with increased IOP independent of glaucoma stage and entity

Association of retinal vessel pathology and brain atrophy in relapsing-remitting multiple sclerosis

BackgroundOptical coherence tomography angiography (OCTA) allows non-invasive assessment of retinal vessel structures. Thinning and loss of retinal vessels is evident in eyes of patients with multiple sclerosis (MS) and might be associated with a proinflammatory disease phenotype and worse prognosis. We investigated whether changes of the retinal vasculature are linked to brain atrophy and disability in MS.Material and methodsThis study includes one longitudinal observational cohort (n=79) of patients with relapsing-remitting MS. Patients underwent annual assessment of the expanded disability status scale (EDSS), timed 25-foot walk, symbol digit modalities test (SDMT), retinal optical coherence tomography (OCT), OCTA, and brain MRI during a follow-up duration of at least 20 months. We investigated intra-individual associations between changes in the retinal architecture, vasculature, brain atrophy and disability. Eyes with a history of optic neuritis (ON) were excluded.ResultsWe included 79 patients with a median disease duration of 12 (interquartile range 2 - 49) months and a median EDSS of 1.0 (0 - 2.0). Longitudinal retinal axonal and ganglion cell loss were linked to grey matter atrophy, cortical atrophy, and volume loss of the putamen. We observed an association between vessel loss of the superficial vascular complex (SVC) and both grey and white matter atrophy. Both observations were independent of retinal ganglion cell loss. Moreover, patients with worsening of the EDSS and SDMT revealed a pronounced longitudinal rarefication of the SVC and the deep vascular complex.DiscussionON-independent narrowing of the retinal vasculature might be linked to brain atrophy and disability in MS. Our findings suggest that retinal OCTA might be a new tool for monitoring neurodegeneration during MS

Toxic retrobulbar neuritis due to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-based chronic sinusitis in the left sphenoid sinus: a case report

Abstract Background Abrupt visual impairment constitutes a medical urgency, necessitating an interdisciplinary diagnostic and therapeutic approach owing to the broad spectrum of potential etiologies, thereby engaging numerous medical specialties. Case presentation A 21-year-old Mixed White and Asian female patient, with medical history of nonsteroidal antiinflammatory drug-exacerbated respiratory disease necessitating previous sinus surgery, reported sudden monocular vision loss. Unremarkable ophthalmological examination of the fellow eye and hematological parameters, save for a slight elevation in lymphocytes and eosinophils, were observed. Imaging studies indicated recurrence of bilateral chronic rhinosinusitis with nasal polyps and a mucocele in the left sphenoid sinus, accompanied by bony structural deficits. Emergency revision sinus surgery, guided by navigation, was promptly performed. The patient received treatment with methylprednisolone, ceftriaxone, cyanocobalamin, pyridoxine, thiamine, and acetylsalicylic acid. During the hospital stay, she developed steroid-induced glaucoma, which was subsequently managed successfully. Negative microbiological swabs, along with pathohistological evidence of increased tissue eosinophilia and the patient’s clinical history, led to the diagnosis of toxic retrobulbar neuritis secondary to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-associated chronic rhinosinusitis of the left sphenoid sinus. Conclusions In cases of acute unilateral vision loss, optic neuritis is a highly probable differential diagnosis and may be induced by pathologies of the paranasal sinuses. Nonsteroidal antiinflammatory drug-exacerbated respiratory disease, a subtype of chronic rhinosinusitis, is associated with type 2 inflammation, which is increasingly recognized for its role in the pathogenesis of bronchial asthma, eosinophilic esophagitis, and atopic eczema. Clinicians should consider chronic rhinosinusitis as a potential differential diagnosis in unilateral visual loss and be cognizant of the rising significance of type 2 inflammations, which are relevant to a variety of diseases. </jats:sec

Association of the retinal vasculature, intrathecal immunity, and disability in multiple sclerosis

Background Optical coherence tomography angiography (OCT-A) is a novel technique allowing non-invasive assessment of the retinal vasculature. During relapsing remitting multiple sclerosis (RRMS), retinal vessel loss occurs in eyes suffering from acute optic neuritis and recent data suggest that retinal vessel loss might also be evident in non-affected eyes. We investigated whether alterations of the retinal vasculature are linked to the intrathecal immunity and whether they allow prognostication of the future disease course. Material and methods This study includes two different patient cohorts recruited at a tertiary German academic multiple sclerosis center between 2018 and 2020 and a cohort of 40 healthy controls. A total of 90 patients with RRMS undergoing lumbar puncture and OCT-A analysis were enrolled into a cross-sectional cohort study to search for associations between the retinal vasculature and the intrathecal immune compartment. We recruited another 86 RRMS patients into a prospective observational cohort study who underwent clinical examination, OCT-A and cerebral magnetic resonance imaging at baseline and during annual follow-up visits to clarify whether alterations of the retinal vessels are linked to RRMS disease activity. Eyes with a history of optic neuritis were excluded from the analysis. Results Rarefication of the superficial vascular complex occured during RRMS and was linked to higher frequencies of activated B cells and higher levels of the pro-inflammatory cytokines interferon-γ, tumor necrosis factor α and interleukin-17 in the cerebrospinal fluid. During a median follow-up of 23 (interquartile range 14 - 25) months, vessel loss within the superficial (hazard ratio [HR] 1.6 for a 1%-point decrease in vessel density, p=0.01) and deep vascular complex (HR 1.6 for a 1%-point decrease, p=0.05) was associated with future disability worsening. Discussion Optic neuritis independent rarefication of the retinal vasculature might be linked to neuroinflammatory processes during RRMS and might predict a worse disease course. Thus, OCT-A might be a novel biomarker to monitor disease activity and predict future disability