Quantifying Putative Retinal Gliosis in Preclinical Alzheimer's Disease.

Purpose: Neuroinflammation plays a significant role in the pathology of Alzheimer's disease (AD). Mouse models of AD and postmortem biopsy of patients with AD reveal retinal glial activation comparable to central nervous system immunoreactivity. We hypothesized that the surface area of putative retinal gliosis observed in vivo using en face optical coherence tomography (OCT) imaging will be larger in patients with preclinical AD versus controls. Methods: The Spectralis II instrument was used to acquire macular centered 20 × 20 and 30 × 25-degrees spectral domain OCT images of 76 participants (132 eyes). A cohort of 22 patients with preclinical AD (40 eyes, mean age = 69 years, range = 60-80 years) and 20 control participants (32 eyes, mean age = 66 years, range = 58-82 years, P = 0.11) were included for the assessment of difference in surface area of putative retinal gliosis and retinal nerve fiber layer (RNFL) thickness. The surface area of putative retinal gliosis and RNFL thickness for the nine sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) map were compared between groups using generalized linear mixed models. Results: The surface area of putative retinal gliosis was significantly greater in the preclinical AD group (0.97 ± 0.55 mm2) compared to controls (0.68 ± 0.40 mm2); F(1,70) = 4.41, P = 0.039; Cohen's d = 0.61. There was no significant difference between groups for RNFL thickness in the 9 ETDRS sectors, P > 0.05. Conclusions: Our analysis shows greater putative retinal gliosis in preclinical AD compared to controls. This demonstrates putative retinal gliosis as a potential biomarker for AD-related neuroinflammation.

Association between retinopathy and risk of dementia in a general Japanese population: the Hisayama Study.

We investigated the association of retinopathy with the risk of dementia in a general older Japanese population. A total of 1709 population-based residents aged 60 years or older without dementia were followed prospectively for 10 years (2007-2017). They underwent color fundus photography in 2007. Retinopathy was graded according to the Modified Airlie House Classification. Main outcome was the Incidence of dementia. A Cox proportional hazards model was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for the risk of dementia by the presence of retinopathy. During the follow-up period, 374 participants developed all-cause dementia. The cumulative incidence of dementia was significantly higher in those with retinopathy than those without (p < 0.05). Individuals with retinopathy had significantly higher risk of developing dementia than those without after adjustment for potential confounding factors (HR 1.64, 95% CI 1.19-2.25). Regarding the components of retinopathy, the presence of microaneurysms was significantly associated with a higher multivariable-adjusted HR for incident dementia (HR 1.94, 95% CI 1.37-2.74). Our findings suggest that, in addition to systemic risk factors, retinal microvascular signs from fundus photography provide valuable information for estimating the risk of developing dementia.

Multimodal Structural and Functional Characterization of Retinal Vasculopathy with Cerebral Leukoencephalopathy.

OBJECTIVE: To describe and quantify the structural and functional consequences of retinal vasculopathy with cerebral leukoencephalopathy (RVCL) on the neurosensory retina. DESIGN: Cross sectional descriptive study from December 2021 to December 2022. PARTICIPANTS: Retinal vasculopathy with cerebral leukoencephalopathy patients (n = 9, 18 eyes) recruited from the RVCL Research Center at Washington University in St. Louis. METHODS: Retinal vasculopathy with cerebral leukoencephalopathy patients underwent comprehensive ophthalmological evaluation including OCT, OCT angiography (OCTA), ultrawidefield fundus imaging, retinal autofluorescence, dark adaptation, electroretinography (ERG), Goldmann kinetic perimetry, and fluorescein angiography (FA). MAIN OUTCOME MEASURES: Comprehensive characterization from various modalities including best-corrected visual acuity, central subfield thickness (µm) from OCT, foveal avascular zone (mm2) from OCTA, dark adaptation rod intercept (seconds), cone response in ERG, and presence or absence of vascular abnormalities, leakage, neovascularization, and nonperfusion on FA. RESULTS: A total of 18 eyes from 9 individuals were included in this study. The best-corrected visual acuity ranged from 20/15 to 20/70. The mean central subfield thickness from OCT was 275.8 µm (range, 217-488 µm). The mean foveal avascular zone (FAZ) from OCTA was 0.65 (range, 0.18-1.76) mm2. On dark adaptometry, the mean time was 5.02 (range, 2.9-6.5) minutes, and 1 individual had impaired dark adaptation. Electroretinography demonstrated mild cone response impairment in 4 eyes. On FA, there was evidence of macular and peripheral capillary nonperfusion in 16 of 18 eyes and notable areas of vascular leakage and retinal edema in 5 of the 18 eyes. CONCLUSIONS: This study illustrates the phenotypic spectrum of disease and may be clinically valuable for aiding diagnosis, monitoring disease progression, and further elucidating the pathophysiology of RVCL to aid in the development of therapies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Bilateral optic nerve infiltration and leukemic retinopathy as initial signs of leukemia relapse with central nervous system involvement in an adult: a case report.

BACKGROUND: We describe a case in which bilateral optic nerve infiltration and leukemic retinopathy were the initial signs of disease relapse in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL) with central nervous system (CNS) involvement. CASE PRESENTATION: A 65-year-old Asian female with Ph+-ALL in complete remission presented at our institution with symptoms of visual disturbance, central scotoma and pain with eye movement in both eyes for a 1-month duration. Ophthalmic examination revealed remarkable optic disc swelling with multiple flame-shaped peripapillary hemorrhages, retinal venous dilation and retinal hemorrhages in both eyes. She was subsequently referred to the treating oncologist and diagnosed with Ph+-ALL relapse with multiple relapsed diseases involving the bone marrow and CNS. After intrathecal (IT) therapy, her visual acuity dramatically improved, and her leukemic infiltrates decreased. CONCLUSIONS: To the best of our knowledge, this is the first case report of ALL relapse with CNS involvement presenting as bilateral optic nerve infiltration and leukemic retinopathy in an adult. Hence, we highlight the priority and sensitivity of ophthalmic examinations, as they are noninvasive methods for detecting leukemia relapse.

Acute macular neuroretinopathy following Valsalva manoeuvre: an insight into the pathophysiology.

Acute macular neuroretinopathy (AMN) affects the outer retina and is most likely induced by non-inflammatory ischaemia of the retinal deep capillary plexus and choriocapillaris. A man in his early 20s developed Valsalva retinopathy following weightlifting at the gym and presented with blurring of vision in the left eye 1 month after the initial retinal haemorrhages had resolved. A diffuse, purplish, donut-shaped, perifoveal lesion was seen on funduscopy and was well defined by an optical coherence tomography angiography (OCTA) en face image in the left eye. Outer retinal changes on optical coherence tomography (OCT) and a dense co-localised scotoma on a visual field (VF) examination confirmed the diagnosis of AMN, and the patient was started on a tapering dose of oral steroids. Improvement was seen in OCT, OCTA and VF during the 6-month follow-up visit. The use of OCTA en face imaging enabled the accurate identification of the lesion in the affected layers of the retina.

Electrodiagnostic Biomarkers in Paraneoplastic Retinopathy.

OBJECTIVE: Paraneoplastic retinopathy (PNR) is a rapid-onset photoreceptor and post-photoreceptor dysfunction triggered by a cross-reaction between antigens expressed by the underlying tumour and retinal proteins. The present study aims to determine the electrodiagnostic biomarkers that support the diagnosis of PNR and evaluate the effect of treatment. METHODS: A retrospective observational case-controlled study including 25 patients with suspected PNR, of which 11 patients were diagnosed with PNR. The presence of PNR was confirmed based on clinical examination, supported by colour fundus photography, fundus autofluorescence imaging, optical coherence tomography, fluorescein angiography, retinal vessel oximetry, colour test, full-field electroretinogram (ffERG), on-/off ERG, S-cone ERG, and multifocal ERG (mfERG). The relationships between the clinical symptomatology and the effect of therapy were evaluated. RESULTS: All PNR patients (Nr: 11) presented with subjective symptoms of newly reported central vision or visual field deterioration. Posterior segment findings showed a severe patchy-like retinal atrophy, attenuation of the retinal vessels, and a waxy optic disc. Optical coherence tomography revealed a discontinued ISe line, and multiple hyperreflective foci. Retinal vessel oxygen saturation was increased. Multifocal ERG revealed reduced central and paracentral responses and ffERG severely attenuated scotopic-, photopic-, on-/off- and S-cone responses. The colour vision test revealed a tritan-tetartan-weakness. Two of the PNR patients underwent rituximab therapy with no further progression and even recovery of electrodiagnostic responses.In 1 nPNR (non-paraneoplastic retinopathy) patient (total Nr: 14) pseudoxanthoma elasticum-related retinopathy was the reason for impaired vision. In 3 of 13 patients with bronchopulmonary cancer a MEK- and FGFR-inhibitor- drug toxicity was the reason for the visual deterioration. CONCLUSION: Careful investigation for signs of central and/or peripheral visual field deterioration must be performed in the presence of history of a co-existing malignancy. The possibility of PNR should be taken into account. The electrodiagnostic biomarkers, suggested in this study, may help to promptly recognise PNR and also to evaluate the effect of implemented therapy.

Retinal Ischemic Perivascular Lesion Reflects Cerebral Small Vessel Disease Burden in Single Subcortical Infarction.

BACKGROUND: Retinal ischemic perivascular lesions (RIPLs) are an indicator of ischemia in the middle retina. We aimed to determine the relationship between RIPLs and single subcortical infarction (SSI). We also investigated the differences in cerebral small vessel disease imaging burden between groups with and without RIPLs in SSI. METHODS AND RESULTS: In this case-control study, we enrolled 82 patients with SSI and 72 nonstroke controls. All participants underwent magnetic resonance imaging and swept-source optical coherence tomography/optical coherence tomography angiography. Small vessel disease markers such as lacunes, cerebral microbleeds, white matter hyperintensity, and perivascular spaces were rated on brain imaging. RIPLs were assessed via swept-source optical coherence tomography. Optical coherence tomography angiography was used to measure the superficial vascular complex and deep vascular complex of the retina. After adjusting for risk factors, the presence of RIPLs was significantly associated with SSI (odds ratio [OR], 1.506 [95% CI, 1.365-1.662], P<0.001). Eyes with RIPLs showed lower deep vascular complex density (P=0.035) compared with eyes without RIPLs in patients with SSI. After adjusting for vascular risk factors, the presence of RIPLs in patients with SSI was associated with an increased periventricular white matter hyperintensity burden (ß=0.414 [95% CI, 0.181-0.647], P<0.001) and perivascular spaces-basal ganglia (ß=0.296 [95% CI, 0.079-0.512], P=0.008). CONCLUSIONS: RIPLs are associated with SSI independent of underlying risk factors. The relationship between the presence of RIPLs and small vessel disease markers provides evidence that RIPLs might be an additional indicator of cerebral ischemic changes.

Posterior segment manifestations of Takayasu arteritis: A narrative review.

Ocular symptoms can be the presenting manifestation of Takayasu arteritis (TA) or could be indicative of disease reactivation. A review of published literature related to posterior segment manifestations of TA by using the keywords "Takayasu arteritis," "ophthalmic manifestations," "retina," "retinopathy," "ocular," "optic nerve," and "optic neuropathy" was performed. In total, 62 case reports and 12 case series were included. The majority of the articles were from Asia (n = 47, 64%). Females outnumbered males in the ratio of 7:1. The mean age of patients was 33 years (range: 8-78 years, SD: 13.5 years). In 58% (n = 41 out of 71) cases, ocular symptoms were the presenting manifestation of the underlying disease. Hypotensive retinopathy was found in 70% of eyes, and hypertensive retinopathy was found in 27%. The mean presenting visual acuity (VA) was +1.03 logMAR (range: -0.12 to 3, SD: 1.07), and at the final follow-up was +1.02 logMAR (range: -0.12 to 3, SD 1.17). VA improved in 34% (n = 29/86), remained stable in 45% (39/86), and worsened in 21% (18/86). The mean follow-up was 9 months (range: 0.5-204, SD: 16 months).

Early diagnosis of sickle cell retinopathy by using ocular coherence tomography in pediatric population (7-18 years) in central India.

BACKGROUND: Sickle cell disease (SCD) is the commonest inherited blood disorder leading to complications occurring due to vaso-occlusion including sight-threatening retinopathy. Retinopathy can be managed if diagnosed early and vision loss can be prevented. Since, very less data are available from India, hence, this study was conducted in children (7-18 years) with SCD to diagnose retinopathy by using ocular coherence tomography (OCT) in subclinical stages. METHODS: This cross sectional single-center study was performed in 7-18 years age group children with SCD without any visual symptoms. Enrolled participants underwent complete ophthalmological examination including macula and optic disc thickness measurements using Cirrus HD-OCT and results were analyzed. RESULTS: Among 55 participants, none had visual impairment. Significant fundoscopy finding (nonproliferative sickle cell retinopathy/NPSR) was found in three patients (5.4%), thinning of central macula in four patients (7.27%), inner macula thinning in eight patients (14.5%), outer macula thinning in one patient (1.81%), retinal nerve fiber layer thinning in five patients (9%), ganglion cell layer to inner plexiform layer thinning in eight patients (14.54%). Overall NPSR was found in 5.4% patients detected with fundoscopy, whereas retinal layer thinning was found in 14 patients (25.4%) using OCT. CONCLUSION: Despite of the significant prevalence of SCR, it is still underdiagnosed complication, leading to thinning of the retina from early ages; thus, its early diagnosis by regular screening using newer diagnostic methods can prevent progression to sight-threatening complications and provide better quality of life for these patients.

Clinical, electrophysiologic and serologic evidence of cancer associated retinopathy preceding a diagnosis of breast cancer.

We report the case of a woman in her 50s who presented headaches, blurred vision, diplopia and loss of peripheral vision. She was treated for normal tension glaucoma based on optic nerve cupping prior to the development of diplopia. Records demonstrated visual field constriction over 4 months despite well-controlled intraocular pressures. Examination revealed decreased visual acuity and visual field constriction. The multifocal electroretinogram was abnormal. After a thorough review of her medical and family history, a concern for cancer-associated retinopathy developed. Blood samples were positive for antiretinal antibodies against 23 kDA and 46 kDA proteins. Cancer screening was recommended as the aetiology for retinopathy was unknown and revealed a left breast lump. Following lumpectomy with adjuvant chemoradiation, her visual acuity normalised and visual field defects completely resolved. This case serves to provide an example that distant systemic symptoms may be a manifestation of the underlying malignancy and the importance of clinical suspicion with prompt evaluation.

Bilateral Takayasu's retinopathy as the initial presentation of Takayasu's arteritis.

We present a case of Takayasu's arteritis in a woman in her 30s, who exhibited visual symptoms and ophthalmic manifestations of the disease, specifically Takayasu's retinopathy stage 4, in both eyes. Despite severe narrowing of all branches of the aortic arch and compromised perfusion in both upper limbs, she had no history of intermittent claudication. Doppler study and CT angiography revealed diffuse circumferential wall thickening of bilateral common carotid, subclavian and axillary arteries. Treatment involved retinal laser photocoagulation and immune suppression. This case underscores that advanced Takayasu's retinopathy can be an initial presentation of Takayasu's arteritis even in a state of severely compromised peripheral limb circulation.

Quantitative assessment of retinal vasculature changes in systemic lupus erythematosus using wide-field OCTA and the correlation with disease activity.

Purpose: To assess the retinal vasculature changes quantitatively using wide-field optical coherence tomography angiography (OCTA) in systemic lupus erythematosus (SLE), and explore its correlation with systemic clinical features. Design: Prospective, cross-sectional, observational study. Participants and controls: Patients with SLE who presented to the Ophthalmology Department of Peking Union Medical College Hospital from November 2022 to April 2023 were collected. The subjects were divided into retinopathy and without retinopathy groups. Age and gender-matched healthy subjects were selected as controls. Methods: Patients with SLE and control subjects were imaged with 24×20 mm OCTA scans centered on the fovea and 6×6 mm OCTA scans centered on the optic disc. The sub-layers of OCTA images were stratified by the built-in software of the device and then the retinal thickness and vessel density were measured automatically. The characteristics of retinal OCTA parameters of SLE and its correlation with systemic clinical indicators of patients without retinopathy were analyzed. Main outcome measures: OCTA parameters, visual acuity, intraocular pressure, and systemic clinical indicators of patients such as disease activity index, autoimmune antibodies, and inflammatory marker levels were collected. Results: A total of 102 SLE patients were included, 24 of which had retinopathy, and 78 had unaffected retina. Wide-field OCTA could effectively detect retinal vascular obstruction, non-perfusion area, and morphological abnormalities in patients with lupus retinopathy. SLE patients without retinopathy had significantly higher retinal superficial vessel density (SVD) in foveal (P=0.02), para-foveal temporal (P=0.01), nasal (P=0.01), peripheral foveal temporal (P=0.02), and inferior areas (P=0.02), as well as subregion temporal (P=0.01) and inferior areas (P=0.03) when compared with healthy controls (n=65 eyes from 65 participants). The area under curve (AUC) value of subregion inferior SVD combined parafoveal temporal SVD was up to 0.70. There was a significantly positive correlation between SVD and disease activity in SLE without retinopathy group. Patients with severe activity had the most significant increase in SVD. Conclusion: Wide-field OCTA can provide a relatively comprehensive assessment of the retinal vasculature in SLE. In the absence of pathological changes of the retina, the SVD was significantly increased and was positively correlated with the disease activity of SLE.

Morphological Biomarkers Related to Visual Acuity in Patients With Radiation Retinopathy Treated With Intravitreal Ranibizumab.

BACKGROUND AND OBJECTIVE: Our objective was to monitor variables via spectral-domain optical coherence tomography (SD-OCT) and identify the most relevant biomarkers related to best-corrected visual acuity (BCVA) in radiation retinopathy (RR). PATIENTS AND METHODS: A post-hoc analysis of the two-year Ranibizumab for Radiation Retinopathy (RRR) trial analyzed vision and OCT parameters including intraretinal fluid, ellipsoid zone (EZ) disruption, retinal pigment epithelium atrophy, hard exudates, retinal hemorrhage, retinal neovascularization, and subfoveal fluid. BCVA and SD-OCT parameters were evaluated by univariate analysis and a mixed-effects model. RESULTS: Forty eyes from the RRR trial were included. Intraretinal cyst vertical size (week 24: P = 0.032; week 48: P = 0.021), neovascularization (week 48: P = 0.028; week 72: P = 0.025), and EZ disruption (week 72: P = 0.029; week 104: P = 0.019) were the clinical parameters most relevant to BCVA by univariate analysis in at least two time points. The mixed-effects model confirmed the relevance of intraretinal cyst vertical size (P = 0.001) and neovascularization (P = 0.001) but not EZ disruption (P = 0.119) over the course of the study. CONCLUSIONS: This study characterizes the course of visual loss in RR by identifying intraretinal cyst vertical size, neovascularization, and EZ disruption as biomarkers of poor BCVA over a span of two years. Larger multicenter studies are needed to confirm these findings. [Ophthalmic Surg Lasers Imaging Retina 2024;55:255-262.].

Autoimmune retinopathy in a patient with smoldering multiple myeloma: a case report.

PURPOSE: Multiple myeloma (MM) is a plasma cell dyscrasia leading to proliferation of monoclonal plasma cells. Ocular involvement in multiple myeloma is uncommon but can occur. The ocular manifestations of MM may include the cornea, uvea, and retinal vasculature. We present a rare case of autoimmune retinopathy associated with smoldering MM. CASE: A 76-year-old female with no significant past medical or ocular history presented with four months of worsening vision, difficulty with night driving, and loss of peripheral vision. Examination was notable for pallor of the optic nerves and vascular attenuation. Visual field testing demonstrated significant and progressive field loss in both eyes. An electroretinogram was extinguished under all conditions. Serum protein electrophoresis showed a significant elevation of IgG with an M-spike, and a subsequent bone marrow biopsy was performed showing 12.5% plasma cells, consistent with the diagnosis of MM. CAR antibody testing was positive for anti-enolase, anti-GAPDH, and anti-Rab6 antibodies, consistent with autoimmune retinopathy. DISCUSSION: Autoimmune retinopathy associated with MM is exceedingly rare. Management of this condition is challenging, as treatment of the underlying disease does not often lead to improvement in visual symptoms. Ultimately, visual prognosis is very poor, and both patients and clinicians should be aware of the guarded visual potential. CONCLUSION: The association of autoimmune retinopathy with multiple myeloma is rare. It is crucial for physicians to be aware of such manifestations to ensure timely and appropriate diagnosis and management for patients.

Sickle Eye Project: a cross-sectional, non-interventional study of the prevalence of visual impairment due to sickle cell retinopathy and maculopathy in the UK.

INTRODUCTION: Sickle cell disease (SCD) is one of the most common genetic disorders in the UK, with over 15 000 people affected. Proliferative sickle cell retinopathy (SCR) is a well-described complication of SCD and can result in significant sight loss, although the prevalence in the UK is not currently known. There are currently no national screening guidelines for SCR, with wide variations in the management of the condition across the UK. METHODS AND ANALYSIS: The Sickle Eye Project is an epidemiological, cross-sectional, non-interventional study to determine the prevalence of visual impairment due to SCR and/or maculopathy in the UK. Haematologists in at least 16 geographically dispersed hospitals in the UK linked to participating eye clinics will offer study participation to consecutive patients meeting the inclusion criteria attending the sickle cell clinic. The following study procedures will be performed: (a) best corrected visual acuity with habitual correction and pinhole, (b) dilated slit lamp biomicroscopy and funduscopy, (c) optical coherence tomography (OCT), (d) OCT angiography where available, (e) ultrawide fundus photography, (f) National Eye Institute Visual Function Questionnaire-25 and (g) acceptability of retinal screening questionnaire. The primary outcome is the proportion of people with SCD with visual impairment defined as logarithm of the minimum angle of resolution ≥0.3 in at least one eye. Secondary outcomes include the prevalence of each stage of SCR and presence of maculopathy by age and genotype; correlation of stage of SCR and maculopathy to severity of SCD; the impact of SCR and presence of maculopathy on vision-related quality of life; and the acceptability to patients of routine retinal imaging for SCR and maculopathy. ETHICS AND DISSEMINATION: Ethical approval was obtained from the South Central-Oxford A Research Ethics Committee (REC 23/SC/0363). Findings will be reported through academic journals in ophthalmology and haematology.