Multimodal diagnostic imaging in primary vitreoretinal lymphoma.

BACKGROUND: Primary vitreoretinal lymphoma (PVRL) is an aggressive lymphoma that may present with protean features and represents a diagnostic challenge. Given that patients with PVRL are at high risk of CNS involvement with a high mortality and morbidity rate, prompt diagnosis is crucial to initiate treatment early in the disease course. A multimodality imaging approach including fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), fluorescein and indocyanine angiography, and electroretinography (ERG) can provide information to establish a diagnosis and provide objective measures for management. We review key findings seen via these imaging modalities in patients with PVRL. OBSERVATIONS: Fundus photography can highlight commonly seen patterns of PVRL including vitritis, subretinal disease, retinal pigment epithelial (RPE) abnormalities, optic nerve edema, retinal detachment, and less typical retinitis-like lesions. FAF can identify characteristic patterns of hyper- and hypoautofluorescent signal abnormalities in the macula. Spectral-domain OCT will demonstrate vitreous cells, RPE nodularity, and hyperreflectivity of the outer retina. The presence of a hyper-reflective band in the subretinal space and infiltrates between the RPE and Bruch's membrane can assist in distinguishing PVRL from choroidal lymphoma. Vertical hyperreflective columns (VHRLs) are another pertinent finding that may represent microinfiltrates of the tumor. OCT has proven to be a particularly useful modality in assessing the progress of treatment in PVRL. Fluorescein angiography can show RPE changes, which include granularity, late staining at the RPE level, and blockage. Indocyanine green angiography (ICGA) primarily shows hypocyanescence, which corresponds to PVRL lesions on fundus photography and may occur secondary to loss of RPE and choriocapillaris. CONCLUSION: While PVRL remains a challenging disease to diagnose and follow, the use of a multimodality imaging approach may assist in establishing a diagnosis. Because of the anatomic spaces PVRL may affect, fundus photography, OCT, FAF, angiography, and ERG can identify key characteristics of the disease, differentiate PVRL from other diseases, and provide baseline information for targeted systemic and local therapies. Further assessment of anatomic and functional targets will aid our clinical application of multimodal imaging in the management of PVRL.

Risk Factors for Retinal Detachment in Acute Retinal Necrosis.

PURPOSE: Retinal detachment (RD) is associated with poor visual outcomes in patients with acute retinal necrosis (ARN). This research was undertaken to assess the risk factors for RD in ARN. DESIGN: Retrospective cohort study. SUBJECTS: Patients diagnosed with ARN at a tertiary referral center from 2010 to 2020. METHODS: A chart review was performed for all clinical and surgical encounters. Univariate and multivariate logistic analyses of demographic and clinical variables associated with RD were performed. Survival analyses with Kaplan-Meier estimates were performed to compare the time to RD in herpes simplex virus (HSV)- and varicella zoster virus (VZV)-associated ARN. MAIN OUTCOME MEASURES: Demographic information, clinical information (including visual acuity [VA]), intraocular pressure (IOP), intraocular inflammation level, the extent of retinitis, incidence and timing of retinal detachment, date of diagnosis, and treatments performed (including intravitreal injections of antiviral medications). RESULTS: Fifty-four eyes of 47 patients who were diagnosed with ARN were included, with equal proportions of eyes (n = 27; 50%) with VZV-ARN and HSV-ARN. Patients with VZV-ARN were, on average, older, more likely to be men, and more likely to be immunosuppressed compared with patients with HSV-ARN. The clinical characteristics, including the initial VA, initial IOP, anterior segment inflammation, clock hours, and posterior extent of retinitis, were similar between eyes with VZV- and HSV-ARN. In the univariate analysis of clinical and demographic variables associated with the development of RD, initial VA (P = 0.0083) and greater clock hours of retinitis (P = 0.009) were significantly associated with RD. These 2 variables remained significant in the multivariate logistic regression; worse VA at presentation had an odds ratio of 2.34 (95% confidence interval [CI], 1.01-5.44; P = 0.042), and greater clock hours of retinitis had an odds ratio of 1.23 (95% CI, 1.02-1.47; P = 0.025). A Kaplan-Meier survival analysis demonstrated no statistical difference in RD-free survival between HSV- and VZV-ARN. CONCLUSIONS: Patients with VZV-ARN were more likely to be older, male, and immunosuppressed compared with those with HSV-ARN, although no clear difference was observed in RD by viral etiology. Poor initial VA and clock hours of retinitis were significantly associated with RD development and may be relevant for patient counseling and prognosis.

Exploring Differences in the Experiences, Perceptions and Reporting of Violent Incidents in Australia by Country of Birth.

Australia's fast-growing migrant population encompasses many groups from culturally and linguistically diverse backgrounds. It is well documented that these groups experience varying pre- and post-migratory challenges. Despite this knowledge, little is known about the extent to which these groups experience and perceive violence and how or whether they seek assistance after such incidents. It is important to identify any potential discrepancies to ensure that services can provide the most targeted supports to victims. Data were collected from the 2016 Australian Bureau of Statistics Public Safety Survey. Using chi-square tests, prevalence, experiences, and perceptions of violence occurring after the age of 15, postincident support, reporting behaviors, and health variables related to violent incidents were compared across three cultural groups arranged by region of birth: born in Australia (BIA), born overseas in main English-speaking countries (BNMESC), and born overseas in non-English-speaking countries (BOC). BOC individuals reported much lower rates of violent victimization compared to BIA and BMSEC individuals. More than two-thirds of each cultural group did not report their most recent experience of violence to police. Violence was most commonly experienced at home, although a higher proportion of BIA individuals experienced violence at an entertainment venue, and a higher proportion of BOC individuals experienced violence outside (i.e., in the street). The contribution of Alcohol/Substances was much higher for BIA and BMESC compared to BOC individuals. BOC individuals experienced more anxiety post-incident, while more BIA individuals sustained physical injuries. A similar proportion of each group sought assistance post-incident, however, more BOC individuals had never told anyone about the incident. Perceptions of the violent incident were generally similar across groups, though fewer BOC individuals perceived the incident to be a crime. Some differences were apparent across cultural groups regarding the prevalence, experiences and reporting of violent incidents. Implications and future research directions are discussed within.

Clinical outcomes following intravitreal methotrexate for primary vitreoretinal lymphoma.

PURPOSE: To describe the visual acuity and anatomic outcomes of intravitreal methotrexate (MTX) for the treatment of primary vitreoretinal lymphoma (PVRL). METHODS: Single-center retrospective case series of patients with a diagnosis of PVRL treated with intravitreal MTX. Patient records were reviewed for demographic information, ocular exam findings, and treatment regimens including number of MTX injections. Clinical outcomes recorded included visual acuity (VA), time to partial (PR) or complete response (CR), disease-free survival, time to relapse, and any CNS progression. RESULTS: Ten eyes of 7 patients (4 male, 6 female) were reviewed. The mean age ± standard deviation (SD) was 70 ± 12 years. Five patients had prior or concomitant diagnosis of primary CNS lymphoma with a history of systemic chemotherapy including MTX. Three eyes (30%) exhibited isolated vitreous involvement, four (40%) had subretinal lesions, and three (30%) presented with both vitreous and subretinal disease. Mean initial logMAR VA was 0.38 ± 0.52 (Snellen visual equivalent 20/50), while mean final logMAR VA ± SD was 0.34 ± 0.27 (Snellen visual equivalent 20/40) with a mean follow-up time of 26 months (Range, 3-49 months). Patients received an average of 6 intravitreal MTX injections (Range 1-10) over the course of treatment. Two patients received concomitant systemic chemotherapy. Mean time to either PR or CR was 57 days, and 6 eyes (60%) exhibited regression with no relapse after local treatment. For the 4 eyes that eventually relapsed, the mean time ± SD to first relapse was 193 days ± 155 days, and one eye experienced a second relapse. Two of 3 patients with subretinal disease showed complete regression with extended follow-up of 1 and 4 years following treatment with less than 3 doses of intravitreal MTX. One patient with PVRL developed CNS lymphoma during the study period. VA remained stable overall between the initial treatment visit, 3, 6, and 12-months (P > 0.05 for paired comparisons of VA over time). CONCLUSIONS: Intravitreal methotrexate was well-tolerated and led to local disease response in the majority of patients at approximately 2 months after initiation of treatment of intraocular lymphoma. Further studies on the efficacy of intravitreal treatment alone versus combined systemic and intravitreal treatment are warranted.

Retinopathy and Systemic Disease Morbidity in Severe COVID-19.

PURPOSE: To assess the prevalence of retinopathy and its association with systemic morbidity and laboratory indices of coagulation and inflammatory dysfunction in severe COVID-19. DESIGN: Retrospective, observational cohort study. METHODS: Adult patients hospitalized with severe COVID-19 who underwent ophthalmic examination from April to July 2020 were reviewed. Retinopathy was defined as one of the following: 1) Retinal hemorrhage; 2) Cotton wool spots; 3) Retinal vascular occlusion. We analyzed medical comorbidities, sequential organ failure assessment (SOFA) scores, clinical outcomes, and laboratory values for their association with retinopathy. RESULTS: Thirty-seven patients with severe COVID-19 were reviewed, the majority of whom were female (n = 23, 62%), Black (n = 26, 69%), and admitted to the intensive care unit (n = 35, 95%). Fourteen patients had retinopathy (38%) with retinal hemorrhage in 7 (19%), cotton wool spots in 8 (22%), and a branch retinal artery occlusion in 1 (3%) patient. Patients with retinopathy had higher SOFA scores than those without retinopathy (8.0 vs. 5.3, p = .03), higher rates of respiratory failure requiring invasive mechanical ventilation and shock requiring vasopressors (p < .01). Peak D-dimer levels were 28,971 ng/mL in patients with retinopathy compared to 12,575 ng/mL in those without retinopathy (p = .03). Peak CRP was higher in patients with cotton wool spots versus those without cotton wool spots (354 mg/dL vs. 268 mg/dL, p = .03). Multivariate logistic regression modeling showed an increased risk of retinopathy with higher peak D-dimers (aOR 1.32, 95% CI 1.01-1.73, p = .04) and male sex (aOR 9.6, 95% CI 1.2-75.5, p = .04). CONCLUSION: Retinopathy in severe COVID-19 was associated with greater systemic disease morbidity involving multiple organs. Given its association with coagulopathy and inflammation, retinopathy may offer insight into disease pathogenesis in patients with severe COVID-19.

Varicella zoster virus anterior uveitis complicated by thalamic stroke.

We report a case of varicella zoster virus (VZV)-associated anterior uveitis in a patient with weight loss, arthritis and signs of inflammatory bowel disease. Her clinical course included the development of a thalamic stroke secondary to VZV cerebral vasculopathy. Following antiviral therapy, the patient's neurologic symptoms recovered and her ophthalmic findings improved.

World Health Organization High Priority Pathogens: Ophthalmic Disease Findings and Vision Health Perspectives.

Recent Ebola epidemics, the ongoing COVID-19 pandemic, and emerging infectious disease threats have highlighted the importance of global infectious diseases and responses to public health emergencies. Ophthalmologists are essential health care workers who provide urgent and emergent vision care services during outbreaks and address the ocular consequences of epidemic and pandemic infectious diseases. In 2017, the World Health Organization (WHO) identified high priority pathogens likely to cause a future epidemic with the goal of guiding research and development to improve diagnostic tests, vaccines, and medicines. These measures were necessary to better inform and respond to public health emergencies. Given the ocular complications associated with emerging infectious diseases, there is a need to recognize the ophthalmic sequelae for future vision health preparedness for potential future outbreaks. The WHO High Priority pathogens list provides a roadmap for ophthalmologists and subspecialty providers that will guide strategic areas of research for clinical care and preparedness for future pandemic threats. This review summarizes these key viral pathogens, summarizes major systemic disease findings, and delineates relevant ocular complications of the WHO High Priority pathogens list, including Crimean-Congo hemorrhagic fever, Filovirus diseases (Ebola virus disease and Marburg hemorrhagic fever), human Coronaviruses, Lassa Fever, Nipah virus infection, Zika, and Rift Valley fever.

Factors affecting final functional outcomes in open-globe injuries and use of ocular trauma score as a predictive tool in Nepalese population.

BACKGROUND: Open globe injury (OGI) is one of the most devastating form of ocular trauma. The aim of the study is to identify the epidemiology and predict visual outcomes in traumatic open globe injuries using ocular trauma score (OTS) and correlate with final visual acuity (VA) at 3 months. METHODS: Patients older than 5 years, presenting to B.P. Koirala Lions Centre for Ophthalmic Studies (BPKLCOS) from March 2016- March 2017 with OGI that met inclusion criteria were evaluated. Patient profile, nature and cause of injury, and time to presentation were recorded. Patients were managed accordingly and followed up to 3 months. An OTS score for each patient was calculated and raw scores were categorized accordingly. The VA after 3 months were compared to the predicted OTS values. RESULTS: Seventy-three eyes of 72 patients were examined. 76 % were male, and the mean age was 26.17 years (median, 23.5 years). The mean time from injury to presentation was < 6 hours (30 patients, 41 %). Thirty-seven eyes (51 %) had zone I trauma, followed by twenty eyes (27 %) with zone II, and sixteen eyes (22 %) with zone III trauma. Sixty-five patients (90 %) were managed surgically, and fifty (68 %) received intravitreal antibiotics with steroid. When compared, the projected VA as per OTS were able to predict actual final visual outcomes in 60 % of the eyes with OGI of various zones. CONCLUSIONS: OTS can be an accurate predictive tool for final visual acuity even with a short follow up period of 3 months; with poor presenting visual acuity, delayed presentation, posterior zones of injury, need for intravitreal injections, endophthalmitis, and globe rupture associated with poorer prognosis.

Advances in the Diagnosis and Management of Acute Retinal Necrosis.

Acute retinal necrosis (ARN) is a devastating syndrome characterized by panuveitis, retinal necrosis, and a high rate of retinal detachment that may result in poor visual outcomes if not promptly diagnosed and treated. ARN is most commonly caused by viruses with the herpesvirus family. Etiologies include varicella-zoster virus, herpes simplex virus, and cytomegalovirus, and may be promptly diagnosed by polymerase chain reaction testing of aqueous or vitreous fluid. The true incidence of ARN is not known due to its rarity; as a result, clinical treatment is often guided by retrospective case series, case reports, and expert opinion. Standard of care has evolved over time but currently includes a combination of systemic and intravitreal antiviral in conjunction with topical or oral steroids and surgical therapy as needed. Combination therapy may reduce the rate of severe vision loss and increase the rate of visual acuity gain, although further studies are needed in this area. In particular for patients with mild to moderate disease, combination therapy may reduce the rate of retinal detachment. Adjunctive therapies including oral corticosteroid and prophylactic laser barricade are incompletely studied, but corticosteroid in particular, may reduce inflammation, which also is involved in the severe disease pathogenesis observed in ARN. This review discusses the advances in diagnosis and treatment of ARN, including management with combination antiviral medication and surgical interventions.

Percutaneous Trigeminal Stimulation for Intractable Facial Pain: A Case Series.

BACKGROUND: Facial pain syndromes can be refractory to medical management and often need neurosurgical interventions. Neuromodulation techniques, including percutaneous trigeminal ganglion (TG) stimulation, are reversible and have emerged as alternative treatment options for intractable facial pain. OBJECTIVE: To report the complication rates and analgesic effects associated with TG stimulation and identify potential predictors for these outcomes. METHODS: A retrospective chart review of 59 patients with refractory facial pain who underwent TG stimulation was conducted. Outcomes following trial period and permanent stimulation were analyzed. Patients with >50% pain relief during trial stimulation received permanent implantation of the stimulation system. RESULTS: Successful trial stimulation was endorsed by 71.2% of patients. During the trial period, 1 TG lead erosion was identified. History of trauma (facial/head trauma and oral surgery) was the only predictor of a failed trial compared to pain of idiopathic etiology (odds ratio: 0.15; 95% CI: 0.03-0.66). Following permanent implantation, approximately 29.6% and 26.5% of patients were diagnosed with lead erosion and infection of the hardware, respectively. TG lead migrations occurred in 11.7% of the patients. The numeric rating scale score showed a statistically significant reduction of 2.49 (95% CI: 1.37-3.61; P = .0001) at an average of 10.8 mo following permanent implantation. CONCLUSION: TG stimulation is a feasible neuromodulatory approach for the treatment of intractable facial pain. Facial/head trauma and oral surgery may predict a nonsuccessful trial stimulation. Future development of specifically designed electrodes for stimulation of the TG, and solutions to reduce lead contamination are needed to mitigate the relatively high complication rate.

Peripheral trigeminal branch stimulation for refractory facial pain: A single-center experience.

OBJECTIVE: Facial pain refractory to medical treatments may benefit from neurosurgical interventions. Only a few studies have reported on the efficacy of peripheral trigeminal stimulation and more specifically supraorbital nerve (SON) and infraorbital nerve (ION) stimulation for the treatment of facial pain. PATIENTS AND METHODS: In the present study, we identified all patients at our institution who underwent SON and/or ION stimulation for treatment of facial pain due to post-herpetic, traumatic or idiopathic etiology. Relevant pre and post-operative outcomes were analyzed. RESULTS: We identified 15 patients who underwent SON and/or ION stimulation. Among them, 12 (80 %) endorsed >50 % pain relief during the trial stimulation period. After a median follow-up of 5.8 months with permanent implantation, 1 patient (8.3 %) was diagnosed with lead erosion and IPG migration, two patients had lead infections (16.7 %) and one (8.3 %) had wound dehiscence. No lead migrations were identified during the long-term follow-up. The VAS score showed a statistically significant reduction from a median pre-operative score of 7 to a post-operative score of 1.8 (p = 0.011), which corresponded to a 74.3 % average pain reduction. CONCLUSION: SON and/or ION stimulation can be an effective treatment for intractable facial pain due to post-herpetic, traumatic or idiopathic etiology; however the complication rate is relatively high. Future prospective studies with longer follow-up periods are warranted.

Dorsal Root Ganglion Stimulation for Thoracic Neuralgia: A Report of Six Cases.

OBJECTIVE: Thoracic neuralgia (TN) is a chronic pain syndrome that can be refractory to pharmacologic intervention and management by pain specialists. Dorsal root ganglion (DRG) stimulation has shown promise as a targeted and effective modality compared to traditional therapies for several indications but has not yet been applied in the thoracic region. This study aims to report the outcomes of off-label thoracic DRG stimulation in patients with refractory TN. METHODS: A retrospective chart review was performed at Emory University Hospital for patients who underwent thoracic DRG stimulation in a two-year period. Relevant outcomes for safety and efficacy were evaluated. RESULTS: Six patients were identified that underwent thoracic DRG stimulation for various etiologies of TN, including post-mastectomy, post-herpetic, and post-abdominoplasty neuralgia. All patients initially underwent trial DRG stimulation with a mean pre-operative visual analogue scale (VAS) (0-10) of 6.8 ± 1.6 (range: 4-8). Four of six patients (67%) were non-responders and did not pursue permanent implantation; two experienced pain with stimulation during the trial, and two patients experienced no significant benefit. In addition, all three patients with post-herpetic neuralgia did not respond to treatment. Two of six patients (33%) responded well to stimulation, elected to receive permanent leads, and reported significant pain relief with VAS scores of 0/10 and 1/10, and 100% reduction in morphine equivalent use. Complications included lead migration and need to reset stimulator programming. CONCLUSIONS: DRG stimulation may be an effective therapy for patients experiencing chronic TN as a result of peripheral nerve injury; however, post-herpetic neuralgia may be unresponsive to this treatment. Future prospective studies are warranted to evaluate the feasibility of this procedure in patients with refractory TN.

The evolving role of antiangiogenic therapies in glioblastoma multiforme: current clinical significance and future potential.

Introduction: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults, but its prognosis remains poor despite significant advances in our understanding of its molecular biology and investigation of numerous treatment modalities. Despite conventional treatment consisting of surgical resection, radiotherapy, and temozolomide marginally prolonging survival, most GBM patients die within 2 years of initial diagnosis. Bevacizumab (Bev) is the best-studied antiangiogenic agent for GBM and currently the only FDA-approved second-line treatment. Areas covered: Areas covered in this review include the molecular pathways of angiogenesis in glioblastoma, specifically the overexpression of vascular endothelial growth factor (VEGF) and robust formation of tumor neovasculature. In addition, this review covers pharmacological targeting of this process as a longstanding attractive clinical strategy, specifically by Bev. Expert opinion: This review attempts to discuss the history of early studies of antiangiogenic treatment for GBM that eventually failed in subsequent studies and the evolving modern role of Bev in the course of treatment for a variety of indications, including symptom control, reduced glucocorticoid use, and improved quality of life.