Medical interventions for traumatic hyphema.

BACKGROUND: Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be associated with significant complications that uncommonly cause permanent vision loss. Complications include elevated intraocular pressure, corneal blood staining, anterior and posterior synechiae, and optic nerve atrophy. People with sickle cell trait or disease may be particularly susceptible to increases in intraocular pressure and optic atrophy. Rebleeding is associated with an increase in the rate and severity of complications. OBJECTIVES: To assess the effectiveness of various medical interventions in the management of traumatic hyphema. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 3); MEDLINE Ovid; Embase.com; PubMed (1948 to March 2022); the ISRCTN registry; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The last date of the search was 22 March 2022. SELECTION CRITERIA: Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. We included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical interventions or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions on age, gender, severity of the closed-globe trauma, or level of visual acuity at time of enrollment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane and assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 23 randomized and seven quasi-randomized studies with a total of 2969 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest. We found no evidence of an effect on visual acuity for any intervention, whether measured within two weeks (short term) or for longer periods. In a meta-analysis of two trials, we found no evidence of an effect of aminocaproic acid on long-term visual acuity (RR 1.03, 95% confidence interval (CI) 0.82 to 1.29) or final visual acuity measured up to three years after the hyphema (RR 1.05, 95% CI 0.93 to 1.18). Oral tranexamic acid appeared to provide little to no benefit on visual acuity in four trials (RR 1.12, 95% CI 1.00 to 1.25). The remaining trials evaluated the effects of various interventions on short-term visual acuity; none of these interventions was measured in more than one trial. No intervention showed a statistically significant effect (RRs ranged from 0.75 to 1.10). Similarly, visual acuity measured for longer periods in four trials evaluating different interventions was also not statistically significant (RRs ranged from 0.82 to 1.02). The evidence supporting these findings was of low or very low certainty. Systemic aminocaproic acid reduced the rate of recurrent hemorrhage (RR 0.28, 95% CI 0.13 to 0.60), as assessed in six trials with 330 participants. A sensitivity analysis omitting two studies not using an intention-to-treat analysis reduced the strength of the evidence (RR 0.43, 95% CI 0.17 to 1.08). We obtained similar results for topical aminocaproic acid (RR 0.48, 95% CI 0.20 to 1.10) in two trials with 131 participants. We assessed the certainty of the evidence as low. Systemic tranexamic acid had a significant effect in reducing the rate of secondary hemorrhage (RR 0.33, 95% CI 0.21 to 0.53) in seven trials with 754 participants, as did aminomethylbenzoic acid (RR 0.10, 95% CI 0.02 to 0.41), as reported in one study. Evidence to support an associated reduction in risk of complications from secondary hemorrhage (i.e. corneal blood staining, peripheral anterior synechiae, elevated intraocular pressure, and development of optic atrophy) by antifibrinolytics was limited by the small number of these events. Use of aminocaproic acid was associated with increased nausea, vomiting, and other adverse events compared with placebo. We found no evidence of an effect on the number of adverse events with the use of systemic versus topical aminocaproic acid or with standard versus lower drug dose.  The number of days for the primary hyphema to resolve appeared to be longer with the use of systemic aminocaproic acid compared with no use, but this outcome was not altered by any other intervention. The available evidence on usage of systemic or topical corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to the small numbers of participants and events in the trials. We found no evidence of an effect between a single versus binocular patch on the risk of secondary hemorrhage or time to rebleed. We also found no evidence of an effect on the risk of secondary hemorrhage between ambulation and complete bed rest. AUTHORS' CONCLUSIONS: We found no evidence of an effect on visual acuity of any of the interventions evaluated in this review. Although the evidence was limited, people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhage. However, hyphema took longer to clear in people treated with systemic aminocaproic acid. There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema, other than possibly to reduce the rate of secondary hemorrhage. The potentially long-term deleterious effects of secondary hemorrhage are unknown. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.

Nonmydriatic Ultra-Widefield Fundus Photography in a Hematology Clinic Shows Utility for Screening of Sickle Cell Retinopathy.

PURPOSE: To determine the feasibility and accuracy of nonmydriatic ultra-widefield (UWF) fundus photographs taken in a hematology clinic setting for screening of sickle cell retinopathy (SCR) DESIGN: Prospective cohort study. METHODS: This single-site study took place at the Johns Hopkins Sickle Cell Center for Adults and the Wilmer Eye Institute. The study population was 90 eyes of 46 consecutive adults with sickle cell disease (SCD). Bilateral nonmydriatic fundus photos taken by clinic personnel during the participants' routine hematology appointment were graded by 2 masked retina specialists at the Wilmer Eye Institute for the presence of nonproliferative SCR (NPSR) and proliferative sickle retinopathy (PSR). A third retina specialist adjudicated in cases of grader disagreement. All participants underwent the standard dilated fundus examination (DFE) within 2 years of acquisition of UWF photographs. The main outcome measure was the sensitivity and specificity of nonmydriatic UWF images for the detection of NPSR and PSR RESULTS: PSR was noted in 19 of 90 eyes that underwent DFE and in 9 of 67 gradable UWF images. Interrater agreement between the 2 graders was moderate, with κ = 0.65 (range 0.43-0.87) for PSR. For gradable UWF photos, the sensitivity and specificity of detecting SCR using the nonmydriatic photos compared with the DFE were 85.2% and 62.5% for NPSR, respectively, and 69.2% and 100% for detection of PSR, respectively. One participant required ophthalmic therapy in both eyes for active sea-fan neovascularization. CONCLUSIONS: UWF imaging shows utility in screening for SCR and may help identify patients with PSR who require a DFE and who may benefit from treatment.

Torpedo-like lesions in the ocular fundi of Gardner syndrome: hiding in plain view.

Background: The coexistence of fundus torpedoes and Gardner syndrome was initially reported in 1989 and 1992 by Gass and Roseman. Gardner syndrome is a dominantly inherited disease characterized by a multitude of potentially lethal gastrointestinal polyps. Over the ensuing quarter century, several publications demonstrated uncommon, but easily recognized, fundus lesions called Torpedo Maculopathy in apparently normal individuals. These fundus abnormalities were thought to be single and isolated without systemic associations. During the same period of time, a variety of nonspecific fundus abnormalities were described in Gardner syndrome, which, in retrospect, included highly specific lesions that closely resembled macular torpedoes and sometimes were indistinguishable from them.Patient and methods: We now report a confirmed case of Gardner syndrome with numerous fundus torpedoes, and carefully analyze the voluminous literature of both Gardner syndrome and Torpedo Maculopathy.Results: We demonstrate shared features of the fundus lesions in both diseases, and hypothesize that they may have genetic as well as ophthalmoscopic similarities in common.Conclusions: We therefore recommend that individuals with classic isolated torpedoes undergo evaluations for mutations in the Gardner gene (Adenomatous polyposis coli) and for the presence of gastrointestinal polyps and other systemic features of Gardner syndrome. We also suggest that apparently normal individuals, who are genetically related to patients with known classic torpedoes, undergo inspection of their fundi for the possible presence of characteristic lesions.

Deep Learning Detection of Sea Fan Neovascularization From Ultra-Widefield Color Fundus Photographs of Patients With Sickle Cell Hemoglobinopathy.

Importance: Adherence to screening for vision-threatening proliferative sickle cell retinopathy is limited among patients with sickle cell hemoglobinopathy despite guidelines recommending dilated fundus examinations beginning in childhood. An automated algorithm for detecting sea fan neovascularization from ultra-widefield color fundus photographs could expand access to rapid retinal evaluations to identify patients at risk of vision loss from proliferative sickle cell retinopathy. Objective: To develop a deep learning system for detecting sea fan neovascularization from ultra-widefield color fundus photographs from patients with sickle cell hemoglobinopathy. Design, Setting, and Participants: In a cross-sectional study conducted at a single-institution, tertiary academic referral center, deidentified, retrospectively collected, ultra-widefield color fundus photographs from 190 adults with sickle cell hemoglobinopathy were independently graded by 2 masked retinal specialists for presence or absence of sea fan neovascularization. A third masked retinal specialist regraded images with discordant or indeterminate grades. Consensus retinal specialist reference standard grades were used to train a convolutional neural network to classify images for presence or absence of sea fan neovascularization. Participants included nondiabetic adults with sickle cell hemoglobinopathy receiving care from a Wilmer Eye Institute retinal specialist; the patients had received no previous laser or surgical treatment for sickle cell retinopathy and underwent imaging with ultra-widefield color fundus photographs between January 1, 2012, and January 30, 2019. Interventions: Deidentified ultra-widefield color fundus photographs were retrospectively collected. Main Outcomes and Measures: Sensitivity, specificity, and area under the receiver operating characteristic curve of the convolutional neural network for sea fan detection. Results: A total of 1182 images from 190 patients were included. Of the 190 patients, 101 were women (53.2%), and the mean (SD) age at baseline was 36.2 (12.3) years; 119 patients (62.6%) had hemoglobin SS disease and 46 (24.2%) had hemoglobin SC disease. One hundred seventy-nine patients (94.2%) were of Black or African descent. Images with sea fan neovascularization were obtained in 57 patients (30.0%). The convolutional neural network had an area under the curve of 0.988 (95% CI, 0.969-0.999), with sensitivity of 97.4% (95% CI, 86.5%-99.9%) and specificity of 97.0% (95% CI, 93.5%-98.9%) for detecting sea fan neovascularization from ultra-widefield color fundus photographs. Conclusions and Relevance: This study reports an automated system with high sensitivity and specificity for detecting sea fan neovascularization from ultra-widefield color fundus photographs from patients with sickle cell hemoglobinopathy, with potential applications for improving screening for vision-threatening proliferative sickle cell retinopathy.

Lower foetal haemoglobin levels at 31- and 34-weeks post menstrual age is associated with the development of retinopathy of prematurity : PacIFiHER Report No. 1 PacIFiHER Study Group (Preterm Infants and Fetal Haemoglobin in ROP).

BACKGROUND/OBJECTIVES: Previous studies have suggested that lower mean foetal haemoglobin (HbF) levels is associated with an increased risk for developing retinopathy of prematurity (ROP). Lower HbF levels may lead to high oxygen exposure to the developing retina thereby increasing the risk of acute ROP. In this study, we characterize the temporal relationship of HbF levels and the development of ROP. SUBJECTS/METHODS: This is a single institution prospective observational cohort study. Preterm infants (born <31 weeks gestational age or <1500 g) with HbF measured at birth (cord blood), 31-, 34-, and 37-weeks post menstrual age (PMA); and at least one ROP exam, were enrolled. RESULTS: A total of 60 preterm infants (28 females, 47%) were enrolled. At 31-, 34-, 37-weeks PMA, infants with ROP (mild = Type 2 or less severe and severe = Type 1 ROP) had statistically lower percentages of HbF than infants with no ROP (28.2 ± 15 and 9.7 ± 2.9 vs 67.1 ± 29.6; p < 0.0001; 23.3 ± 14.7 and 32.5 vs 60.1 ± 25; p < 0.005; 31.9 ± 15.8 and 41.6 vs 60.2 ± 20.0; p < 0.0019). Infants with HbF levels in the lowest tercile at 31-weeks PMA were 7.6 times more likely to develop mild and severe ROP (95% CI 2.1-24.0, p value = 0.0006) and this risk increased to 12.3 times (95% CI: 2.6-59.0, p value = 0.0017) at 34-weeks PMA. CONCLUSIONS: Low HbF levels at 31- and 34-weeks PMA are associated with significantly increased risk of developing ROP. The decrease in HbF precedes the development of ROP and may be important in its pathogenesis.

Epidemiology and outcomes of hyphema: a single tertiary centre experience of 180 cases.

PURPOSE: To characterize the epidemiology and outcomes of hyphema. METHODS: Retrospective case series. Medical records from patients with traumatic and spontaneous hyphema seen at the Wilmer Eye Institute, Johns Hopkins, from 2011 through 2017 were evaluated. Aetiology, demographics, clinical characteristics, complications, management and outcomes were ascertained. Multivariable logistic regression was used to identify factors associated with elevated intraocular pressure (IOP), rebleeding and poor outcome (final visual acuity ≤ 20/40) in traumatic hyphema. A safe frequency of follow-up was retrospectively determined. RESULTS: Traumatic hyphema (n = 152) was more common in males (78%) and adults (55%), with sports/recreational activities being the most frequent cause (40%). Elevated IOP was the most common complication (39%). Rebleeding occurred in seven patients (5%) and was more likely with a higher IOP on presentation (OR:1.1; p = 0.004). Thirty-seven patients (24%) had a poor outcome, mostly due to traumatic sequelae such as cataract (32%) or posterior segment involvement (30%). A poor outcome was more likely with worse presenting visual acuity (OR: 9.1; p = 0.001), rebleeding (OR: 37.5; p = 0.035) and age > 60 years (OR: 16.0; p = 0.041). Spontaneous hyphema (n = 28) did not have a gender predominance and was more common in adults > 60 years (71%). The most common cause was iris neovascularization (61%). Complications and visual outcomes were worse compared with traumatic hyphema. CONCLUSIONS: Traumatic hyphema continues to be common in young males engaging in sports, necessitating increased awareness for preventive eyewear. Older age and rebleeding can lead to poor outcomes. Elevated IOP at presentation predisposes to rebleeding and warrants frequent follow-up. Otherwise, routine follow-up at days 1, 3, 5, 7 and 14 is sufficient for uncomplicated cases.

Clinical Characteristics and Outcomes of Hyphema in Patients with Sickle Cell Trait: 10-Year Experience at the Wilmer Eye Institute.

PURPOSE: To report the clinical characteristics, complications, and outcomes of hyphema in patients with sickle cell trait (SCT). DESIGN: Retrospective case series. METHODS: Medical records of SCT patients (confirmed by hemoglobin electrophoresis) presenting with hyphema at the Wilmer Eye Institute over 10 years (January 2008 through December 2017) were reviewed in detail. Data were collected regarding etiology, demographics, clinical course and management. Main outcome measures included intraocular pressure (IOP) and visual acuity (VA). RESULTS: A total of 14 black patients (males: 57%; median age: 20 years) were included in the study with a median follow-up of 4 months (range: 1 week to 6 years). Ten patients had traumatic hyphema with a mean presenting VA of approximately 1.10 logMAR (Snellen equivalent=20/250) and a mean presenting IOP of 40 mmHg. Nine of them required medical intervention to lower IOP, and six of them ultimately required surgical intervention, primarily in the form of anterior chamber paracentesis and/or washout. The mean time to achieve IOP control was 3 days, and the mean final VA was approximately 0.10 logMAR (Snellen Equivalent=20/25). Four patients had non-traumatic hyphema with a mean presenting VA of approximately 1.8 logMAR (Snellen equivalent=20/1260) and a mean presenting IOP of 31 mmHg. Three of them required medical intervention to lower IOP, and two of them ultimately required surgical intervention. Overall, seven patients underwent anterior chamber washout, six needed an anterior chamber paracentesis to lower the IOP, two required tube shunt placement procedures and one patient underwent a trabeculectomy. The mean time to achieve IOP control was 5 days, and the mean final VA was approximately 0.80 logMAR (Snellen equivalent=20/125). CONCLUSION: Patients with SCT are likely to develop elevated IOP in the setting of hyphema, with a majority requiring one or more surgical interventions to achieve IOP control.

Optical coherence tomography angiography of astrocytic hamartoma demonstrates intrinsic vascularity.

PURPOSE: To evaluate the findings of astrocytic hamartoma in the setting of gyrate atrophy, including details of optical coherence tomography angiography (OCTA). OBSERVATIONS: Multimodal imaging was obtained on a 20-year-old woman with genetically-confirmed gyrate atrophy. Dilated fundus exam was performed, followed by ultra-widefield color and green autofluorescence imaging and OCTA of bilateral peripapillary and optic disc lesions. Clinical and imaging findings were consistent with gyrate atrophy. The bilateral peripapillary and optic disc lesions had a glistening, translucent, and mulberry-like appearance. OCTA imaging of these lesions clearly demonstrated an intrinsic vascular network and hyporeflective spaces within the lesion, which could not be seen on routine examination. CONCLUSIONS AND IMPORTANCE: OCTA was used to noninvasively diagnose astrocytic hamartoma in this patient with gyrate atrophy by showing the intrinsic vasculature and hyporeflective spaces of the lesion. This imaging modality can help differentiate astrocytic hamartoma from other lesions that typically lack intrinsic vascularity, such as optic disc drusen.

Neuroradiologic manifestations of COVID-19: what the emergency radiologist needs to know.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global pandemic with a wide spectrum of clinical signs and symptoms. Neurologic manifestations are relatively common, with severe cases often demonstrating striking findings on neuroimaging. Because the neuroradiologic findings may be the first evidence of COVID-19, the emergency radiologist has a critical role to play in not only the detection and management of the disease but also in the safety of other patients and hospital staff. Therefore, radiologists, especially those who specialize in emergency radiology, need to be aware of the neuroradiologic manifestations of COVID-19.

Cerebrovascular Disease in COVID-19.

Coronavirus disease 19 (COVID-19) is a pandemic originating in Wuhan, China, in December 2019. Early reports suggest that there are neurologic manifestations of COVID-19, including acute cerebrovascular disease. We report a case of COVID-19 with acute ischemic stroke. To our knowledge, this is the first reported case of COVID-19-related cerebral infarcts that includes brain imaging at multiple time points and CT angiography. There is a growing body of published evidence that complications of COVID-19 are not limited to the pulmonary system. Neuroradiologists should be aware of a wide range of neurologic manifestations, including cerebrovascular disease.

ETDRS Grading of Diabetic Retinopathy: Still the Gold Standard?

This article aims to provide a narrative history of the evolution, modification, and legacy of the Early Treatment Diabetic Retinopathy Study classification system.

Epidemiology of Hyphema-Related Emergency Department Visits in The United States Between 2006 and 2015.

PURPOSE: To describe epidemiological trends, risk factors, and hospital-associated charges for patients presenting with hyphema to emergency departments (EDs) throughout the United States (U.S.). METHODS: Cross-sectional analysis of all hyphema-related ED cases in the U.S. Nationwide Emergency Department Sample (NEDS) between 2006 and 2015 to determine population-based incidence rates, patient demographics, visit characteristics and associated charges. RESULTS: Between 2006 and 2015, there were a total of 16,222 cases with hyphema as primary visit diagnosis (0.52 ED visits per 100,000 population). The mean (SD) age at presentation was 37.4 (24.8) years, and males accounted for 66.2% of these cases. Trauma (n = 4,994, 30.8%) was the most frequently identified etiology, with sports-related injuries as important contributor. On multivariate analysis, traumatic hyphema was more likely for patients aged 5-14 years (Odds ratio [OR] = 1.88 [95% Confidence interval [CI]: 1.04-3.40, p = 0.04]) than 0-4 years, males (OR = 1.33 [95% CI: 1.09-1.62, p = 0.01]), in May through September (OR = 1.66-1.93 [95% CI: 1.08-3.05, p = 0.005-0.03]),and for those in the highest income quartile (OR = 1.42 [95% CI: 1.10-1.83, p = 0.01]). Visits were less likely for patients aged ≥55 years (OR = 0.49 [95% CI: 0.25-0.994, p = 0.03]) than 0-4 years. During the study period, hyphema accounted for $21 million in ED associated and $9 million in inpatient charges. CONCLUSION: ED visits with hyphema as primary diagnosis occur at an annual rate of 0.52 per 100,000 population. Young males are particularly at risk and there has been an increase in the number of sports-related injuries which may represent a modifiable cause. Hyphema management costs $3 million in hospital-related charges annually.

Medical interventions for traumatic hyphema.

BACKGROUND: Traumatic hyphema is the entry of blood into the anterior chamber (the space between the cornea and iris) subsequent to a blow or a projectile striking the eye. Hyphema uncommonly causes permanent loss of vision. Associated trauma (e.g. corneal staining, traumatic cataract, angle recession glaucoma, optic atrophy, etc.) may seriously affect vision. Such complications can lead to permanent impairment of vision. People with sickle cell trait/disease may be particularly susceptible to increases of elevated intraocular pressure. If rebleeding occurs, the rates and severity of complications increase. OBJECTIVES: To assess the effectiveness of various medical interventions in the management of traumatic hyphema. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 6); MEDLINE Ovid; Embase.com; PubMed (1948 to June 2018); the ISRCTN registry; ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The date of the search was 28 June 2018. SELECTION CRITERIA: Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. In this review, we included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical intervention or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions regarding age, gender, severity of the closed-globe trauma, or level of visual acuity at the time of enrollment. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data for the primary outcomes, visual acuity and time to resolution of primary hemorrhage, and secondary outcomes including: secondary hemorrhage and time to rebleed; risk of corneal blood staining, glaucoma or elevated intraocular pressure, optic atrophy, or peripheral anterior synechiae; adverse events; and duration of hospitalization. We entered and analyzed data using Review Manager 5. We performed meta-analyses using a fixed-effect model and reported dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD). MAIN RESULTS: We included 20 randomized and seven quasi-randomized studies with a total of 2643 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest.We found no evidence of an effect on visual acuity for any intervention, whether measured within two weeks (short term) or for longer periods. In a meta-analysis of two trials, we found no evidence of an effect of aminocaproic acid on long-term visual acuity (RR 1.03, 95% confidence interval (CI) 0.82 to 1.29) or final visual acuity measured up to three years after the hyphema (RR 1.05, 95% CI 0.93 to 1.18). Eight trials evaluated the effects of various interventions on short-term visual acuity; none of these interventions was measured in more than one trial. No intervention showed a statistically significant effect (RRs ranged from 0.75 to 1.10). Similarly, visual acuity measured for longer periods in four trials evaluating different interventions was also not statistically significant (RRs ranged from 0.82 to 1.02). The evidence supporting these findings was of low or very low certainty.Systemic aminocaproic acid reduced the rate of recurrent hemorrhage (RR 0.28, 95% CI 0.13 to 0.60) as assessed in six trials with 330 participants. A sensitivity analysis omitting two studies not using an intention-to-treat analysis reduced the strength of the evidence (RR 0.43, 95% CI 0.17 to 1.08). We obtained similar results for topical aminocaproic acid (RR 0.48, 95% CI 0.20 to 1.10) in two studies with 121 participants. We assessed the certainty of these findings as low and very low, respectively. Systemic tranexamic acid had a significant effect in reducing the rate of secondary hemorrhage (RR 0.31, 95% CI 0.17 to 0.55) in five trials with 578 participants, as did aminomethylbenzoic acid as reported in one study (RR 0.10, 95% CI 0.02 to 0.41). The evidence to support an associated reduction in the risk of complications from secondary hemorrhage (i.e. corneal blood staining, peripheral anterior synechiae, elevated intraocular pressure, and development of optic atrophy) by antifibrinolytics was limited by the small number of these events. Use of aminocaproic acid was associated with increased nausea, vomiting, and other adverse events compared with placebo. We found no evidence of an effect in the number of adverse events with the use of systemic versus topical aminocaproic acid or with standard versus lower drug dose. The number of days for the primary hyphema to resolve appeared to be longer with the use of systemic aminocaproic acid compared with no use, but this outcome was not altered by any other intervention.The available evidence on usage of systemic or topical corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to the small numbers of participants and events in the trials.We found no evidence of an effect between a single versus binocular patch or ambulation versus complete bed rest on the risk of secondary hemorrhage or time to rebleed. AUTHORS' CONCLUSIONS: We found no evidence of an effect on visual acuity by any of the interventions evaluated in this review. Although evidence was limited, it appears that people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhaging. However, hyphema took longer clear in people treated with systemic aminocaproic acid.There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema other than possibly to reduce the rate of secondary hemorrhage. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as binocular patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.

Ocular Histopathology and Immunohistochemical Analysis in the Oldest Known Individual with Autosomal Dominant Vitreoretinochoroidopathy.

PURPOSE: To assess the immunohistochemical and histopathological changes in a subject with Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC). DESIGN: Case study. PARTICIPANT: Ninety two year-old Caucasian male with ADVIRC. METHODS: The subject was documented clinically for 54 Years. The retina/choroid complex of the right eye was evaluated with cryosections stained with hematoxylin and eosin or periodic acid schiff reagent. Cryosections were also evaluated with immunofluorescence or alkaline phosphatase immunohistochemistry (IHC) using primary antibodies against bestrophin1, GFAP, PEDF, RPE65, TGFß, VEGF, and vimentin. The left retina and choroid were evaluated as flat mounts using immunofluorescence. UEA lectin was used to stain viable vasculature. MAIN OUTCOME MEASURES: The immunohistochemical and histopathological changes in retina and choroid from a subject with ADVIRC. RESULTS: The subject had a heterozygous c.248G>A variant in exon 4 of the BEST1 gene. There was widespread chorioretinal degeneration and atrophy except for an island of spared RPE monolayer in the perimacula/macula OU. In this region, some photoreceptors were present, choriocapillaris was spared, and retinal pigment epithelial cells were in their normal disposition. There was a Muller cell periretinal membrane throughout much of the fundus. Bestrophin-1 was not detected or only minimally present by IHC in the ADVIRC RPE, even in the spared RPE area. Beyond the island of retained RPE monolayer on Bruch's membrane (BrMb), there was migration of RPE into the neuro-retina, often ensheathing blood vessels and producing excessive matrix within their perivascular aggregations. CONCLUSIONS: The primary defect in ADVIRC is in RPE, the only cells in the eye that express the BEST1 gene. The dysfunctional RPE cells may go through epithelial/mesenchymal transition as they migrate from BrMb to form papillary aggregations in the neuro-retina, often ensheathing blood vessels. This may be the reason for retinal blood vessel nonperfusion. Migration of RPE from BrMb was also associated with attenuation of the choriocapillaris.

Multimodal Retinal Imaging in Incontinentia Pigmenti Including Optical Coherence Tomography Angiography: Findings From an Older Cohort With Mild Phenotype.

Importance: Incontinentia pigmenti (IP) is a rare, X-linked dominant disease with potentially severe ocular complications that predominantly affect the peripheral retina. However, little is known about its effects on the macula. Objective: To describe the structural and vascular abnormalities observed in the maculas of patients with IP and to correlate these findings with peripheral pathologies. Design, Setting, and Participants: Prospective, cross-sectional study at Wilmer Eye Institute, Johns Hopkins University. Five participants with a clinical diagnosis of IP were included and underwent multimodal imaging with ultra-wide-field fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT), and OCT angiography. Main Outcomes and Measures: The structural and vascular abnormalities observed on spectral-domain OCT and OCT angiography and their correlation with peripheral pathologies seen on ultra-wide-field FA. Results: A total of 9 eyes from 5 patients (median age, 20.5 years; range, 8.4-54.2 years) were included. Median Snellen visual acuity was 20/32 (range, 20/16 to 20/63). ultra-wide-field FA-identified retinal vascular abnormalities in all 7 eyes in which FA was obtained. These abnormalities included microaneurysms, areas of nonperfusion, and vascular anastomoses, most of which were peripheral to the standard view of 30° FA with peripheral sweeps. Structural abnormalities were observed in 6 eyes on spectral-domain OCT, including inner retinal thinning and irregularities in the outer plexiform layer. Optical coherence tomography angiography abnormalities were noted in all 9 eyes, including decreased vascular density, abnormal vascular loops, and flow loss in the superficial and deep plexuses, which corresponded to areas of retinal thinning on spectral-domain OCT. Conclusions and Relevance: Although our study is limited by the small sample size, the findings suggest that multimodal imaging is useful for detecting structural and vascular abnormalities that may not be apparent on ophthalmoscopy in patients with IP. Macular pathologies, especially a decrease in vascular density on OCT angiography, are common. Further studies are needed to characterize further the association between macular and peripheral abnormalities in patients with IP.

Expression of the angiogenic mediator, angiopoietin-like 4, in the eyes of patients with proliferative sickle retinopathy.

The recent success of therapies directly targeting the angiogenic mediator, vascular endothelial growth factor (VEGF), for the treatment of proliferative diabetic retinopathy has encouraged clinicians to extend the use of anti-VEGF therapies for the treatment of another ischemic retinal vascular disease, proliferative sickle cell retinopathy (PSR), the most common cause of irreversible blindness in patients with sickle cell disease. However, results from case reports evaluating anti-VEGF therapies for PSR have been mixed. This highlights the need to identify alternative therapeutic targets for the treatment of retinal neovascularization in sickle cell patients. In this regard, angiopoietin-like 4 (ANGPTL4) is a novel angiogenic factor regulated by the transcription factor, hypoxia-inducible factor 1, the master regulator of angiogenic mediators (including VEGF) in ischemic retinal disease. In an effort to identify alternative targets for the treatment of sickle cell retinopathy, we have explored the expression of ANGPTL4 in the eyes of patients with PSR. To this end, we examined expression and localization of ANGPTL4 by immunohistochemistry in autopsy eyes from patients with known PSR (n = 5 patients). Complementary studies were performed using enzyme-linked immunosorbent assays in aqueous (n = 8; 7 patients, 2 samples from one eye of same patient) and vitreous (n = 3 patients) samples from a second group of patients with active PSR. We detected expression of ANGPTL4 in neovascular tissue and in the ischemic inner retina in PSR, but not control, eyes. We further observed elevated expression of ANGPTL4 in the aqueous and vitreous of PSR patients compared to controls. These results suggest that ANGPTL4 could contribute to the development of retinal neovascularization in sickle cell patients and could therefore be a therapeutic target for the treatment of PSR.