Eleonora M. Lad

Intravitreal injection of therapeutic agents.

Background: Intravitreal injection (IVI) with administration of various pharmacological agents is a mainstay of treatment in ophthalmology for endopthalmitis, viral retinitis, age-related macular degeneration, cystoid macular edema, diabetic retinopathy, uveitis, vascular occlusions, and retinal detachment. The indications and therapeutic agents are reviewed in this study. Methods: A search of the English, German, and Spanish language MEDLINE database was conducted. A total of 654 references spanning the period through early 2008 were individually evaluated. Results: The advantage of the IVI technique is the ability to maximize intraocular levels of medications and to avoid the toxicities associated with systemic treatment. Intravitreal injection has been used to deliver several types of pharmacological agents into the vitreous cavity: antiinfective and antiinflammatory medications, immunomodulators, anticancer agents, gas, antivascular endothelial growth factor, and several others. The goal of this review is to provide a detailed description of the properties of numerous therapeutic agents that can be delivered through IVI, potential complications of the technique, and recommendations to avoid side effects. Conclusion: The IVI technique is a valuable tool that can be tailored to the disease process of interest based on the pharmacological agent selected. This review provides the reader with a comprehensive summary of the IVI technique and its multitude of uses.

Visual Loss After Spine Surgery : A Population-Based Study

Study Design. Retrospective cohort study using National inpatient sample administrative data. Objective. To determine national estimates of visual impairment and ischemic optic neuropathy after spine surgery. Summary of Background Data. Loss of vision after spine surgery is rare but has devastating complications that has gained increasing recognition in the recent literature. National population-based studies of visual complications after spine surgery are lacking. Methods. All patients from 1993 to 2002 who underwent spine surgery (Clinical Classifications software procedure code: 3, 158) and who had ischemic optic neuropathy (ION) (ICD9-CM code 377.41), central retinal artery occlusion (CRAO) (ICD9-CM code 362.31) or non-ION, non-CRAO perioperative visual impairment (ICD9-CM codes: 369, 368.4, 368.8–9368.11–13) were included. Univariate and multivariate analysis were performed to identify potential risk factors. Results. The overall incidence of visual disturbance after spine surgery was 0.094%. Spine surgery for scoliosis correction and posterior lumbar fusion had the highest rates of postoperative visual loss of 0.28% and 0.14% respectively. Pediatric patients (<18 years) were 5.8 times and elderly patients (>84 years) were 3.2 times more likely than, patients 18 to 44 years of age to develop non-ION, non-CRAO visual loss after spine surgery. Patients with peripheral vascular disease (OR = 2.0), hypertension (OR = 1.3), and those who received blood transfusion (OR = 2.2) were more likely to develop non-ION, non-CRAO vision loss after spine surgery. Ischemic optic neuropathy was present in 0.006% of patients. Hypotension (OR = 10.1), peripheral vascular disease (OR = 6.3) and anemia (OR = 5.9) were the strongest risk factors identified for the development of ION. Conclusion. We used multivariate analysis to identify significant risk factors for visual loss after spine surgery. National population-based estimate of visual impairment after spine surgery confirms that ophthalmic complications after spine surgery are rare. Since visual loss may be reversible in the early stages, awareness, evaluation and prompt management of this rare but potentially devastating complication is critical.

Incidence of Retinopathy of Prematurity in the United States: 1997 through 2005

PURPOSE To determine the incidence of retinopathy of prematurity (ROP) based on a national database and to identify baseline characteristics, demographic information, comorbidities, and surgical interventions. DESIGN Retrospective study based on the National Inpatient Sample from 1997 through 2005. METHODS The National Inpatient Sample was queried for all newborn infants with and without ROP. Multivariate logistic regression was used to predict risk factors for ROP. RESULTS Thirty-four million live births were recorded during the study period. The total ROP incidence was 0.17% overall and 15.58% for premature infants with length of stay of more than 28 days. Our results conclusively demonstrated the importance of low birth weight as a risk for ROP development in infants with length of stay of more than 28 days, as well as association with respiratory conditions, fetal hemorrhage, intraventricular hemorrhage, and blood transfer. An interesting finding was the protective effect conferred by hypoxia, necrotizing enterocolitis, and hemolytic disease of the newborn. Infants with ROP had a higher incidence of undergoing laser photocoagulation therapy, pars plana vitrectomy, and scleral buckle surgery. CONCLUSIONS The current study represents a large, retrospective analysis of newborns with ROP. The multivariate analysis emphasizes the role of birth weight in extended-stay infants, as well as respiratory conditions, fetal hemorrhage, intraventricular hemorrhage, and blood transfer.

Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP): 12-month experience with telemedicine screening

Background/aims: To report the 1-year experience of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative. Methods: Forty-two consecutively enrolled infants who met ROP examination criteria were screened between 1 December 2005 through 30 November 2006 with the RetCam II and evaluated by the SUNDROP reading centre at Stanford University. Nurses obtained five images in each eye. All patients also received a dilated examination by the author within 1 week of discharge from the hospital. Outcomes included referral-warranted disease, need for treatment and anatomical outcomes. Referral-warranted disease was defined as any Early Treatment Retinopathy of Prematurity (ROP) Disease Type 2 or greater, or any plus disease. A retrospective analysis of 84 eyes, 131 unique examinations and 1315 unique images from the SUNDROP archival data is reported here. Results: In the initial 12-month period, the SUNDROP telemedicine screening initiative had not missed any referral warranted ROP. Calculated sensitivity and specificity was 100% and 95%, respectively. No patient progressed to retinal detachment or other adverse outcomes. Conclusions: The SUNDROP telemedicine screening initiative for ROP has proven to have a high degree of sensitivity and specificity for identification of referral warranted disease. These results indicate that telemedicine may improve accessibility of ROP screening.

Abundance of infiltrating CD163+ cells in the retina of postmortem eyes with dry and neovascular age-related macular degeneration

PurposePrior research in animal models has suggested that retinal macrophages play an important role in age-related macular degeneration (AMD), but studies have insufficiently characterized the distribution of retinal macrophages in various stages of human AMD.MethodsIn this case series, we analyzed H&E, periodic acid-Schiff, and CD163 and CD68 immunostained slides from 56 formaldehyde-fixed, paraffin-embedded autopsy eyes of patients over age 75: 11 age-matched, normal eyes, and 45 AMD eyes.ResultsQualitative analysis of the macula and retinal periphery revealed that all eyes contained a significant number of CD163+ cells but a negligible number of CD68+ cells. In normal eyes and eyes with thin or infrequent basal laminar deposits, CD163+ cells were restricted to the inner retina. In contrast, in AMD eyes with thick basal deposits, choroidal neovascular membranes, and geographic atrophy, qualitatively there was a marked increase in the number and size of the CD163+ cells in the outer retina, sub-retinal, and sub-retinal pigment epithelium space in the macula.ConclusionsThe changes in number and localization of retinal CD163+ cells in eyes with intermediate-severe AMD support a key role for macrophages in the pathogenesis and progression of the disease. A larger, quantitative study evaluating the distribution of macrophage subpopulations in postmortem AMD eyes is warranted.

Stanford University network for diagnosis of retinopathy of prematurity (SUNDROP): 36-month experience with telemedicine screening.

BACKGROUND AND OBJECTIVE to report the 36-month experience of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative. PATIENTS AND METHODS retrospective analysis of the SUNDROP archival data between December 1, 2005, and November 30, 2008, to evaluate this diagnostic technology for retinopathy of prematurity (ROP) screening. A total of 230 consecutively enrolled infants meeting ROP examination criteria were screened with the Ret-Cam II (Clarity Medical Systems, Pleasanton, CA) and evaluated by the SUNDROP reading center at Stanford University. Outcomes included referral-warranted ROP, treatment-warranted ROP, and anatomic outcomes. RESULTS in the initial 36-month period, the SUNDROP telemedicine initiative did not miss any treatment-warranted ROP. A total of 230 infants (460 eyes) were imaged, resulting in 1,059 examinations and 10,921 unique images. Ten infants were identified with referral-warranted ROP: nine underwent laser photocoagulation and one regressed spontaneously. The sensitivity was 100% with a specificity of 99.5%. No patient progressed to retinal detachment or other adverse outcomes. CONCLUSION the SUNDROP telemedicine screening initiative for ROP has demonstrated high reliability for identification of treatment-warranted disease. All cases of treatment-warranted disease were captured. There were no adverse outcomes.

Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP): 24-month experience with telemedicine screening

Purpose:  To report the 24‐month experience of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative.

Wnt-Signaling in Retinal Development and Disease

The Wnt-signaling pathway is a known regulator of stem cell maintenance, cellular proliferation and differentiation, and cancer development in various tissues. Wnt proteins play a central role during various stages of retinal development; retinal field establishment, retinal and hyaloid vasculogenesis, cornea and lens development, eye field formation, and maintenance of retinal stem cell and neuronal specification in many species are Wnt-regulated processes. Uncontrolled Wnt signaling may cause retinal diseases such as familial exudative vitroretinopathy, retinitis pigmentosa, and Norries disease, further underscoring the importance of the Wnt-signaling pathway in the retina. This review summarizes major developments and discoveries regarding the role of the Wnt-signaling pathway as it pertains to retinal development and disease.

Anti-VEGF treatment patterns for neovascular age-related macular degeneration among medicare beneficiaries.

PURPOSE To examine the use of anti-vascular endothelial growth factor (VEGF) therapy in clinical practice among patients with neovascular age-related macular degeneration (AMD). DESIGN Retrospective cohort study. METHODS Among 459 237 Medicare beneficiaries, we identified anti-VEGF treatment using claims for intravitreal injections of anti-VEGF medications with a supporting diagnosis of neovascular AMD. We used the cumulative incidence function to calculate the frequency of anti-VEGF treatments and treatment visits for neovascular AMD per treated eye in the first and second year after the initial anti-VEGF injection. We calculated the mean number of treatments and treatment visits per eye using the mean frequency function. Rates of discontinuation were estimated using Kaplan-Meier methods. RESULTS The mean number of injections was 4.3 in the first year, with 58% of patients receiving 1-4 injections, 20% receiving 5-6 injections, and 22% receiving 7 or more injections. Among patients who received 7 or more injections during the first year, 31% received a comparable number during the second year, and 12% received no injections. Of patients who received 1-4 injections during the first year, 70% received no injections and 24% received 1-4 injections during the second year. Rates of anti-VEGF discontinuation were 57% within 12 months and 71% within 24 months. CONCLUSIONS The frequency of anti-VEGF injections for neovascular AMD was lower than that recommended by large-scale clinical trials, and rates of discontinuation were high. National practice patterns in anti-VEGF therapy for patients with neovascular AMD do not reflect optimal treatment strategies suggested by recent clinical trial evidence.

Wide-field retinal optical coherence tomography with wavefront sensorless adaptive optics for enhanced imaging of targeted regions

The peripheral retina of the human eye offers a unique opportunity for assessment and monitoring of ocular diseases. We have developed a novel wide-field (>70°) optical coherence tomography system (WF-OCT) equipped with wavefront sensorless adaptive optics (WSAO) for enhancing the visualization of smaller (<25°) targeted regions in the peripheral retina. We iterated the WSAO algorithm at the speed of individual OCT B-scans (~20 ms) by using raw spectral interferograms to calculate the optimization metric. Our WSAO approach with a 3 mm beam diameter permitted primarily low- but also high- order peripheral wavefront correction in less than 10 seconds. In preliminary imaging studies in five normal human subjects, we quantified statistically significant changes with WSAO correction, corresponding to a 10.4% improvement in average pixel brightness (signal) and 7.0% improvement in high frequency content (resolution) when visualizing 1 mm (~3.5°) B-scans of the peripheral (>23°) retina. We demonstrated the ability of our WF-OCT system to acquire non wavefront-corrected wide-field images rapidly, which could then be used to locate regions of interest, zoom into targeted features, and visualize the same region at different time points. A pilot clinical study was conducted on seven healthy volunteers and two subjects with prodromal Alzheimers disease which illustrated the capability to image Drusen-like pathologies as far as 32.5° from the fovea in un-averaged volume scans. This work suggests that the proposed combination of WF-OCT and WSAO may find applications in the diagnosis and treatment of ocular, and potentially neurodegenerative, diseases of the peripheral retina, including diabetes and Alzheimers disease.