Peripheral Exudative Hemorrhagic Chorioretinopathy (PEHCR): Diagnostic and Therapeutic Challenges.

Background and Objectives: Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a peripheral retinal vascular abnormality that is likely underreported. We review the differential diagnoses, etiology, and treatment options for PEHCR. Methods: We present a case of an asymptomatic 72-year-old female referred following left eye fundus photography finding of the peripheral lesion. Results: Fundus photography demonstrated a large temporal pigment epithelial detachment (PED) with adjacent fibrovascular membrane. Optical coherence tomography (OCT) confirmed the PED with trace subretinal fluid. Fluorescein angiography (FA) demonstrated early and late hypofluorescence of the PED with late leakage of the adjacent temporal fibrovascular membrane. Observation was elected, visual acuity remained unaffected, and the PED spontaneously resolved. Conclusions: Due to the peripheral location, patients often present as asymptomatic; however, vision loss can occur due to vitreous hemorrhage or extension of subretinal fluid, hemorrhage, or exudate to the macula. Commonly, these lesions are referred with concern for choroidal melanoma due to their large, dark, elevated presentation in the peripheral retina. Multimodal testing using B-scan, FA, and OCT is important in establishing the proper diagnosis. PEHCR lesions can often be observed without treatment, though intravitreal injection of anti-VEGF is increasingly used to prevent secondary causes of vision loss.

STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS: NOVEL FINDINGS AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY ANALYSIS.

PURPOSE: To present novel findings in stellate nonhereditary idiopathic foveomacular retinoschisis, including the largest series of optical coherence tomography angiography findings to date. METHODS: A retrospective case series with multimodal imaging was obtained and reviewed. RESULTS: All three patients were women, aged 59-63. Two cases were unilateral, and one was bilateral. Vision ranged from 20/20 to 20/60 in the affected eyes. Peripheral retinoschisis was observed in all three patients. All patients were followed for a minimum of 1 year. In one case, progressive macular retinoschisis leading to foveal involvement was observed over two years, with an associated vision decline from 20/25 to 20/60. Attempted interventions included topical dorzolamide in all cases and intravitreal bevacizumab in one patient; however, no treatment effect was observed. The foveal avascular zone size was within normal limits (mean 280 µ m). In all stellate nonhereditary idiopathic foveomacular retinoschisis eyes, the retinoschisis cavities were nonvascular. CONCLUSION: Novel findings regarding stellate nonhereditary idiopathic foveomacular retinoschisis include the progressive nature of foveal involvement and the lack of response to topical dorzolamide and intravitreal bevacizumab. Foveal avascular zone was normal in all eyes, consistent with the relatively preserved vision in these cases. Retinoschisis cavities were nonvascular in all eyes, a finding which may give insight into the mechanism of this disease.

Retinal Thickness and Morphology Changes on OCT in Youth with Type 2 Diabetes: Findings from the TODAY Study.

Objective: To evaluate changes in retinal thickness and morphology using OCT in youth with type 2 diabetes (T2D) and to identify systemic biomarkers correlating with these changes. Design: Retrospective subgroup analysis of a prospective study. Participants: Participants who underwent OCT imaging in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial and its follow-up study TODAY2. Methods: In 2010-2011 (TODAY) and 2017-2018 (TODAY2), 6 × 6-mm macular volume OCT scans were acquired, segmented, and analyzed to generate total retinal thickness, inner retinal thickness, and outer retinal thickness. The main retinal morphologies graded were intraretinal cystoid spaces, subretinal fluid, and posterior vitreous detachment (PVD). Main Outcome Measures: Changes in total and individual retinal layer thickness and development of abnormal vitreomacular morphology between TODAY and TODAY2. Results: Participants had a mean age of 17.9 ± 2.4 years and glycated hemoglobin (HbA1c) of 8.2 ± 2.8% in TODAY and a mean age of 25.0 ± 2.4 years and mean HbA1c of 9.5 ± 2.8% in TODAY2. Longitudinally between assessments, there were overall decreases in outer retinal thickness from 167.2 ± 11.5 microns to 158.4 ± 12.8 microns (P < 0.001) and in photoreceptor thickness from 30.3 ± 2.9 microns to 29.8 ± 4.1 microns (P = 0.04) in the central subfield, while in the inner subfield, we noted a decrease in outer retinal thickness from 150.5 ± 10.1 microns to 144.9 ± 10.5 microns (P < 0.001) and an increase in inner retinal thickness from 136.9 ± 11.5 microns to 137.4 ± 12.6 microns (P = 0.01). Multivariate analysis showed that in the center subfield, HbA1c increases were associated with increases in total retinal thickness (r: 0.67, P = 0.001), whereas fasting glucose was positively correlated with inner retinal thickness (r: 0.02, P = 0.02). In the inner subfield, both systolic (r: -0.22, P < 0.001) and diastolic (r: -0.22, P = 0.003) blood pressures were negatively correlated with total retinal thickness. There was an increase in PVD (18.9%) and cystoid spaces (4.2%). Conclusions: Youth with T2D develop retinal thickness changes on OCT, including increases in total retinal and inner retinal thickness in the center subfield that correlate with HbA1c and fasting glucose, respectively. Taken together with the increased prevalence of abnormal vitreomacular morphology in this cohort at risk, these findings emphasize the importance of controlling risk factors to prevent the development of sight-threatening retinal complications.

Purtscher-Like Retinopathy with Cardioembolic Stroke: Case Report and Literature Review.

Purtscher-like retinopathy (PUR) is a rare condition characterized by sudden vision loss with associated retinal white patches thought to be due to precapillary arteriolar occlusion. We present a case of PUR associated with a cardioembolic stroke in a patient following temporary cessation of anticoagulant therapy for a surgical procedure. Our patient presented with multiple risk factors for PUR and classic signs and symptoms including multiple peripapillary white retinal lesions near arterioles and sudden unilateral decrease in visual acuity. Optical coherence tomography showed inner retinal hyperreflectivity and thinning consistent with inner retinal ischemia, and fluorescein angiography showed delayed retinal filling. Her complement C5 factor was elevated on laboratory testing. Brain magnetic resonance imaging showed acute/subacute left occipital lobe ischemia thought to be from a cardioembolic stroke. Shortly prior to visual symptoms, our patient's apixaban was held due to surgical drainage of a gluteal abscess. This case highlights the rare occurrence of PUR associated with cardioembolic stroke and the importance of cerebral imaging in a patient presenting with PUR of uncertain etiology.

The obesity paradox: Retinopathy, obesity, and circulating risk markers in youth with type 2 diabetes in the TODAY Study.

AIM: To understand the relationship of obesity and 27 circulating inflammatory biomarkers to the prevalence of non-proliferative diabetic retinopathy (NPDR) in youth with type 2 diabetes. METHODS: Youth with type 2 diabetes who participated in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study were followed for 2-6.5 years. Digital fundus photographs were obtained in the last year of the study. Blood samples during the study were processed for inflammatory biomarkers, and these were correlated with obesity tertiles and presence of retinopathy. RESULTS: Higher BMI was associated with an increase in circulating levels of metabolic biomarkers including high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor 1 (PAI-1), fibrinogen, LDL-cholesterol (LDL-C) and Apolipoprotein B (ApoB), tumor necrosis factor receptors 1 and 2 (TNFR-1 and -2), interleukin 6 (IL-6), E-selectin, and homocysteine, as well as a decrease in the metabolic risk markers HDL-cholesterol (HDLC), and insulin-like growth factor binding protein 1 (IGFBP-1). Although NPDR risk decreased with increasing obesity, it was not associated with any of the measured biomarkers. CONCLUSIONS: Circulating levels of measured biomarkers did not elucidate the "obesity paradox" of decreased NPDR in the most obese participants in the TODAY study. TRIAL REGISTRATION: clinicaltrials.govNCT00081328.

Redefining the Spectrum of Pentosan Polysulfate Retinopathy: Multimodal Imaging Findings from a Cross-Sectional Screening Study.

PURPOSE: There is growing evidence of a direct association between pentosan polysulfate (PPS) therapy and the development of macular changes. Using standardized visual acuity (VA) testing and multimodal imaging, we investigated the impact of PPS therapy on vision and described an expanded spectrum of imaging findings among PPS users. DESIGN: Cross-sectional screening study. PARTICIPANTS: Thirty-nine patients who were current or recent users of PPS. METHODS: The participants underwent a brief eye examination and answered a comprehensive medical and ophthalmic history questionnaire. Color fundus photography, fundus autofluorescence (FAF), and spectral-domain OCT (SD-OCT) were performed. The images were evaluated by expert graders at Wisconsin Reading Center. Abnormalities were categorized as definite toxicity (DT) if seen on both FAF and SD-OCT and as questionable toxicity (QT) if seen on either FAF or SD-OCT. MAIN OUTCOME MEASURES: ETDRS and Snellen VA, the dosage and duration of PPS exposure, and the prevalence of retinal toxicity on imaging. RESULTS: The mean ETDRS and Snellen VA of the study cohort were 85 letters and 20/22, respectively. The mean PPS daily dose was 282 mg (range, 88-400 mg), whereas the mean cumulative dose was 915 g (range, 19-3650 g) over a mean period of 8.8 years (range, 2 months-25 years). There was evidence of retinopathy in 41% of the eyes; DT was identified in 24 eyes (31%) and QT in 8 eyes (10%). Retinal pigment epithelium (RPE) abnormalities (thickening or thinning or both) were present in all eyes with DT. Retinal pigment epithelium atrophy was seen in 7 eyes (9%). In addition to well-established findings, the unique SD-OCT features of this cohort included interdigitation zone abnormalities and the presence of a flying saucer-type defect. Fundus autofluorescence abnormalities were seen in 24 eyes (30.8%), with 20 (66.7%) of these exhibiting abnormalities located outside the central subfield and extending beyond the arcades. CONCLUSIONS: Findings from the masked grading of multimodal imaging at a centralized reading center suggest a wider phenotypic spectrum of structural abnormalities among patients taking PPS. Macular changes selectively involve the RPE and outer retina, with a range of findings often seen beyond the arcades. The subtle and atypical findings in this cohort should prompt clinicians to consider lowering the threshold for diagnosing PPS retinopathy.

Complications of Intra-Arterial tPA for Iatrogenic Branch Retinal Artery Occlusion: A Case Report through Multimodal Imaging and Literature Review.

Background and Objectives: To document, through multimodal imaging, the post-procedural clinical course and visual outcome of a patient who received intra-arterial tissue plasminogen activator (tPA) for acute iatrogenic branch retinal artery occlusion (BRAO), and to review the literature and guidelines regarding the use of tPA for retinal arterial occlusions. Methods: A 28-year-old female patient who sustained an iatrogenic BRAO and subsequently received intra-arterial tPA was followed through her post-interventional course of 3 months with serial exams and multimodal imaging, including color fundus photography, visual field testing, spectral domain optical coherence tomography (SD-OCT), and OCT angiography (OCT-A). Results: A patient with history of left internal cerebral artery (ICA) aneurysm and baseline visual acuity (VA) of 20/20 developed an acutely symptomatic BRAO after undergoing a neuroendovascular procedure and was acutely treated with tPA through the left ophthalmic artery. At two weeks follow-up, a central posterior pole hemorrhage was noted although VA was preserved. A superior altitudinal defect was shown on automated perimetry. VA dropped to 20/50 at 7 weeks follow-up and hyperreflective material deep to the attachment between the posterior hyaloid and the internal limiting membrane (ILM) consistent with hemorrhage was noted on SD-OCT. At 11 weeks follow-up, VA returned to 20/20, SD-OCT revealed a membrane bridging the foveal depression, OCT-A showed decreased vascularity in the inferior macula, and the visual field defect was stable by automated perimetry. Conclusions: Intraocular hemorrhage is a possible complication of intra-arterial tPA administration for BRAO, and a careful analysis of risks, benefits, and goals of this procedure must be considered by both provider and patient before such intervention.

Spectral Domain OCT Predictors of Visual Acuity in the Study of COmparative Treatments for REtinal Vein Occlusion 2: SCORE 2 Report 15.

PURPOSE: To evaluate the association between baseline demographic and spectral domain OCT (SD-OCT) features with visual acuity (VA) in the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2) over 2 years. DESIGN: Post hoc analysis of prospective clinical trial data. PARTICIPANTS: A total of 362 SCORE2 participants with macular edema secondary to central retinal (CRVO) or hemiretinal vein occlusion (HRVO). METHODS: Spectral domain OCT volume scans were assessed at the SCORE2 reading center at baseline, month 01 (M01), month 06 (M06), month 12 (M12), and month 24 (M24) for central subfield thickness (CST), subretinal fluid, intraretinal fluid, vitreoretinal interface abnormalities, disorganization of retinal inner layers (DRIL), and ellipsoid zone (EZ) within the central subfield (CSF). MAIN OUTCOME MEASURES: Visual acuity at M06, M12, and M24. RESULTS: Mean baseline age was 68.9 years. Mean VA at M01 was 63.2 letters, and CST was 299.7 µm. At M01, subretinal fluid was seen in 28.5% intraretinal fluid in 67.2%, DRIL was seen in 73.8%, mostly within the CSF, and the EZ was absent in 9.8 and patchy in 31.7%. In multivariate analysis including all M01 demographics and SD-OCT parameters and their association with VA at M06, M12, and M24, VA at M01 remained significant across all time points up to M24 (P < 0.001). CONCLUSIONS: In this 2-year follow-up of eyes that were treated with both per protocol and off protocol for RVO, VA at M01 was an important predictor of long-term vision and change in vision. Establishing predictors of visual recovery helps identify causes for poor responders to treatment in patients with RVO.

Autoimmune retinopathy: findings and limitations from optical coherence tomography angiography.

BACKGROUND AND OBJECTIVE: To report novel findings and limitations from optical coherence tomography angiography (OCTA) in the evaluation of autoimmune retinopathy (AIR). STUDY DESIGN: We retrospectively reviewed features of five patients diagnosed with AIR and five controls. OCTA scans were obtained and manually segmented to provide accurate measurements of foveal avascular zone (FAZ), vessel density, and retinal thickness at different levels. RESULTS: The total retina and superficial vessel density throughout the whole scan were similar between AIR and controls (p = 0.14 and p = 0.11), whereas deep vessel density was decreased in AIR compared controls (p = 0.02). Decreased vessel density was most pronounced in the parafoveal and perifoveal areas (p = 0.01 and p = 0.01). AIR patients also had reduction of total retinal thickness in the perifoveal zone (p = 0.03), corresponding to outer retinal thinning (p = 0.001). CONCLUSION: This small series shows that AIR patients have reduced deep vessel density, particularly in the parafoveal and perifoveal regions and a decrease in macular thickness. These findings show correlation with the classic "flying saucer" sign seen on OCT.

Non-paraneoplastic autoimmune retinopathy: multimodal testing characteristics of 13 cases.

BACKGROUND: Non-paraneoplastic autoimmune retinopathy (npAIR) is a rare autoimmune disease that primarily affects retinal photoreceptor function and results in profound and often times permanent vision loss. Delay in diagnosis and treatment initiation may contribute to the poor visual prognosis. METHODS: A retrospective chart review of all patients diagnosed with autoimmune retinopathy at the University of Wisconsin-Madison Eye Clinics between January 2012 and January 2017 was performed. Twenty eyes of 15 patients had evidence of any form of autoimmune retinopathy through a combination of symptoms, ocular findings, visual fields, optical coherence tomography, fundus autofluorescence, full-field and multifocal electroretinography, and serum anti-retinal antibodies. Clinical records were also analyzed for demographic data, systemic comorbidities, visual acuity, treatment employed, and disease progression. RESULTS: We identified 18 eyes from 13 patients who fit the criteria for non-paraneoplastic autoimmune retinopathy. Sixty-nine percent of patients were female with a mean age of symptom onset of 56.9 ± 20.3 years. Sixty-seven percent of eyes had an associated autoimmune condition, most commonly hypothyroidism. Serum testing revealed a preponderance of antibodies against carbonic anhydrase II, while imaging revealed characteristic changes. Fundus autofluorescence most commonly showed hyperautofluorescence around the macula. The delayed diagnosis led to a larger reduction in the horizontal extent of ellipsoid zone in 1-mm perifoveal area on optical coherence tomography with resulting visual decline. There was no difference in the change of visual acuity when stratifying for patients with autoimmune conditions (p = 0.52) or treatment status (p = 0.50). None of the patients who received treatment developed contralateral eye involvement or experienced disease progression based on visual acuity or symptoms. CONCLUSION: Non-paraneoplastic autoimmune retinopathy has a wide and often challenging to diagnose spectrum of clinical symptoms and imaging findings. Immunosuppressive therapy can be considered empiric in the face of a suggestive presentation and can be initiated after an evaluation of clinical findings and multimodal testing, though treatment does not appear to affect regeneration of the ellipsoid zone on OCT or impact visual acuity. Treatment should be primarily used to prevent disease progression and contralateral eye involvement. TRIAL REGISTRATION: N/A.

Multimodal imaging of refractory Candida chorioretinitis progressing to endogenous endophthalmitis.

BACKGROUND: Endogenous fungal endophthalmitis is a serious vision-threatening condition that occurs in immunosuppressed patients with candidemia. FINDINGS: We report a complicated case of Candida albicans chorioretinitis that progressed to endophthalmitis. The patient required intravitreal and systemic anti-fungal medications with pars plana vitrectomy for successful treatment. Multimodal imaging using fundus photography, fluorescein angiography, spectral domain optical coherence tomography, and fundus autofluorescence was obtained throughout treatment. These modalities localized the Candida infection in the choroid, penetrating Bruch's membrane, the retinal pigment epithelium, and the retina to enter the vitreous cavity. This infectious route resulted in loss of the retinal pigment epithelium, photoreceptors, and outer retinal layers, with scar formation that resulted in vision loss and increased future risk of choroidal neovascular membranes. CONCLUSIONS: Multimodal imaging of C. albicans chorioretinitis allows for accurate diagnosis, assessment of response to therapy, and prognosis for visual recovery and future complications.

Small hyperreflective intraretinal material observable on spectral-domain optical coherence tomography in high myopia.

With the rapid adoption of spectral-domain optical coherence tomography (SD-OCT) in clinical practice and recent advances in technology, SD-OCT has become an important tool for detecting and managing retinal pathology. The diagnosis of degenerative changes in pathologic myopia can sometimes be difficult and delayed, as the clinical presentation may be subtle. In this series, SD-OCT proved useful in the detection of small hyperreflective intraretinal material in cases in which retinal changes are minimally visible and may explain visual changes that may not have been otherwise elucidated. The results show that SD-OCT in conjunction with clinical examination may provide useful information in the management of patients with pathologic myopia.

Progression of hydroxychloroquine toxic effects after drug therapy cessation: new evidence from multimodal imaging.

IMPORTANCE: Given the infrequent occurrence of hydroxychloroquine toxic effects, few data are available about the presenting features and long-term follow-up of patients with hydroxychloroquine retinopathy, making it difficult to surmise the clinical course of patients after cessation of drug treatment. OBJECTIVE: To report functional and structural findings of hydroxychloroquine retinal toxic effects after drug therapy discontinuation. DESIGN: A retrospective medical record review was performed to identify patients taking hydroxychloroquine who were screened for toxic effects from January 1, 2009, through August 31, 2012, in the eye centers of Northwestern University and the University of Southern California. SETTING: Northwestern University Sorrel Rosin Eye Center, Chicago, Illinois, and the Doheny Eye Institute at the University of Southern California, Los Angeles. PARTICIPANTS: Seven consecutive patients diagnosed as having hydroxychloroquine retinal toxic effects. MAIN OUTCOME AND MEASURE: Retinal toxic effects. RESULTS: Seven patients (1 man and 6 women) with a mean age of 55.9 years (age range, 25-74 years) developed retinal toxic effects after using hydroxychloroquine for a mean of 10.4 years (range, 3-19 years). Fundus examination revealed macular pigmentary changes in all 7 patients, corresponding to abnormal fundus autofluorescence (FAF). On spectral domain optical coherence tomography, there was outer retinal foveal resistance (preservation of the external limiting membrane and the photoreceptor layer) in 6 patients. After drug therapy discontinuation, 5 patients experienced outer retinal regeneration (3 subfoveally and 2 parafoveally), with associated functional visual improvement on static perimetry in 2 patients. Over time, FAF remained stable in 3 patients, whereas the remaining patients had a pattern of hypoautofluorescence that replaced areas of initial hyperautofluorescence (2 patients) and enlargement of the total area of abnormal FAF (2 patients). CONCLUSIONS AND RELEVANCE: Preservation of the external limiting membrane carries a positive prognostic value in hydroxychloroquine toxic effects because it may be associated with regeneration of the photoreceptor layer and with potential functional visual improvement on static perimetry. The patterns of abnormal FAF persist despite cessation of the medication, with enlargement of the total area of abnormal FAF being the hallmark of severe toxic effects. Relative foveal resistance in hydroxychloroquine toxic effects was supported by this case series. These findings emphasize the importance of early detection and the need for correlating clinical observations with multimodal imaging, particularly FAF and spectral domain optical coherence tomography.

An evidence-based review of vascular endothelial growth factor inhibition in pediatric retinal diseases: part 2. Coats' disease, best disease, and uveitis with childhood neovascularization.

Vascular endothelial growth factor (VEGF) is an important factor in the pathogenesis of multiple retinal neovascular disorders. This report focuses on the quality and depth of new evidence for the use of VEGF inhibitors in selected pediatric ocular diseases, including Coats' disease, Best disease, and childhood uveitis. Because much of the literature comprises case reports and retrospective case series, the level of evidence supporting its use as a primary treatment option, or even as adjuvant therapy, is low. The standard of care is treatment of the underlying disorder to prevent neovascularization (retinal or subretinal), vitreous hemorrhage, or subsequent retinal detachment. However, these complications may not present until late in the disease course. It may then be useful to treat with these agents. Prospective studies are warranted to further elucidate the role of anti-VEGF therapy in these diseases.

An evidence-based meta-analysis of vascular endothelial growth factor inhibition in pediatric retinal diseases: part 1. Retinopathy of prematurity.

Recently there has been interest in the novel, off-label use of anti-vascular endothelial growth factor (anti-VEGF) agents for various stages of retinopathy of prematurity (ROP). The authors report on the quality and depth of new evidence published from 2009 to 2011 concerning the treatment of retinopathy of prematurity (ROP) with bevacizumab (Avastin; Genentech Inc., South San Francisco, CA) as either primary or adjunctive treatment for ROP. There is significant variability in the evidence, quality, and design of the studies available in the literature. There has been a trend in the scientific literature of the past 2 years toward larger, multi-center, randomized studies investigating the role of bevacizumab in the treatment of ROP. More recent evidence suggests that monotherapy with intravitreal bevacizumab may be a viable first-line treatment for select cases of zone I ROP and possibly for posterior zone II disease. Adjunctive treatment with bevacizumab may enhance outcomes in patients treated with laser photocoagulation or pars plana vitrectomy. However, there are significant concerns regarding its long-term safety profile. Further prospective studies are warranted to more fully determine the role of anti-VEGF therapy in this disease.

Primary neuroendocrine tumor of the orbit progressing to neoplastic meningitis.

A 60-year-old man presented with multiple cranial neuropathies and an identifiable left orbital lesion along the course of the supraorbital nerve. The pathologic features of the excised orbital lesion were consistent with a poorly differentiated primary neuroendocrine carcinoma. Four years after his diagnosis, the patient succumbed to neoplastic meningitis. No other primary tumor site was identified or clinically apparent during his illness.