Comparison of Retinal Imaging Techniques in Individuals with Pulmonary Artery Hypertension Using Vessel Generation Analysis.

(1) Background: Retinal vascular imaging plays an essential role in diagnosing and managing chronic diseases such as diabetic retinopathy, sickle cell retinopathy, and systemic hypertension. Previously, we have shown that individuals with pulmonary arterial hypertension (PAH), a rare disorder, exhibit unique retinal vascular changes as seen using fluorescein angiography (FA) and that these changes correlate with PAH severity. This study aimed to determine if color fundus (CF) imaging could garner identical retinal information as previously seen using FA images in individuals with PAH. (2) Methods: VESGEN, computer software which provides detailed vascular patterns, was used to compare manual segmentations of FA to CF imaging in PAH subjects (n = 9) followed by deep learning (DL) processing of CF imaging to increase the speed of analysis and facilitate a noninvasive clinical translation. (3) Results: When manual segmentation of FA and CF images were compared using VESGEN analysis, both showed identical tortuosity and vessel area density measures. This remained true even when separating images based on arterial trees only. However, this was not observed with microvessels. DL segmentation when compared to manual segmentation of CF images showed similarities in vascular structure as defined by fractal dimension. Similarities were lost for tortuosity and vessel area density when comparing manual CF imaging to DL imaging. (4) Conclusions: Noninvasive imaging such as CF can be used with VESGEN to provide an accurate and safe assessment of retinal vascular changes in individuals with PAH. In addition to providing insight into possible future clinical translational use.

Orbital Implants Receiving Food and Drug Administration Premarket Notification.

PURPOSE: This perspective explores the Food and Drug Administration (FDA) 510(k) program, occasionally referred to as premarket notification, which facilitates faster marketing of Class II medical devices, such as orbital implants by demonstrating "substantial equivalence" to previously approved devices. This allows for FDA clearance, rather than FDA approval of orbital implants via comparison to currently marketed implants rather than clinically proven safety standards. METHODS: Utilizing the FDA's publicly available 510(k) Premarket Notification database, we conducted a thorough search of FDA-cleared orbital implants dating back to the inception of the 510(k) process in 1976. RESULTS: We found that 29 orbital implants received 510(k) FDA clearance between 1987 and 2022. Four of the 29 implants were recalled. Only 9 of 29 implants had available data on their predicate or comparison devices; of these 9, 3 implants received clearance based on devices that were subsequently recalled. CONCLUSIONS: This investigation into premarket approval of orbital implants identifies a shortcoming in the FDA 510(k) approval process. Long-term implant-associated morbidity is difficult to predict during premarket analysis but is further complicated for 510(k) cleared implants since devices approved based on substantial equivalence to recalled devices may not be automatically recalled. Clinicians should be aware of the approval process for the devices they select, and review of the 510(k) process, especially as it applies to substantial equivalence to devices subsequently recalled is warranted.

Retinal vessel changes in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is classically considered an isolated small vessel vasculopathy of the lungs with peripheral pulmonary vascular obliteration. Systemic manifestations of PAH are increasingly acknowledged, but data remain limited. We hypothesized that retinal vascular changes occur in PAH. PAH subjects underwent retinal fluorescein angiography (FA) and routine disease severity measures were collected from the medical record. FA studies were analyzed using VESsel GENerational Analysis (VESGEN), a noninvasive, user-interactive computer software that assigns branching generation to large and small vessels. FAs from controls (n = 8) and PAH subjects (n = 9) were compared. The tortuosity of retinal arteries was higher in PAH subjects compared to unmatched controls (1.17, 95% confidence interval: [1.14, 1.20] in PAH vs. 1.13, 95% CI: [1.12, 1.14] in controls, p = 0.01). Venous tortuosity was higher and more variable in PAH (1.17, 95% CI: [1.14, 1.20]) compared to controls (1.13, 95% CI: [1.12, 1.15]), p = 0.02. PAH subjects without connective tissue disease had the highest degree of retinal tortuosity relative to controls (arterial, p = 0.01; venous, p = 0.03). Younger PAH subjects had greater retinal arterial tortuosity, which attenuated with age and was not observed in controls. Retinal vascular parameters correlated with some clinical measures of disease in PAH subjects. In conclusion, PAH subjects exhibit higher retinal vascular tortuosity. Retinal vascular changes may track with pulmonary vascular disease progression. Use of FA and VESGEN may facilitate early, noninvasive detection of PAH.

Bilateral Occlusive Retinal Vasculitis in a Patient with Dermatomyositis.

A 48-year-old woman with a history of dermatomyositis (DMS) presented with 2 weeks of worsening myalgias, weakness, and diffuse edema following cessation of her systemic immunosuppression and subsequently developed severe bilateral vision loss consistent with bilateral frosted branch angiitis. Multimodal imaging was performed, and the patient was successfully treated with pulse-dose steroids and intravenous immunoglobulin, as well as intravitreal aflibercept. Ophthalmic involvement of DMS is typically limited to episcleritis, conjunctivitis, and uveitis. We present an uncommon case of bilateral occlusive retinal vasculitis with frosted branch angiitis in a patient with DMS. The significant improvement anatomically and in visual acuity in our patient suggests a role of combined anti-vascular endothelial growth factor and systemic immunosuppression in the management of DMS -related frosted branch angiitis. We suggest that retinal vasculitis should be considered in patients with known DMS and acute vision loss, with prompt referral for ophthalmologic evaluation.

Discontinuation and nonpublication of interventional clinical trials conducted in ophthalmology.

OBJECTIVE: Discontinuation of interventional clinical trials and nonpublication of completed trials represent a waste of already scarce resources. We sought to identify the prevalence of discontinuation and nonpublication of interventional clinical trials conducted in ophthalmology patients. METHODS: A retrospective, cross-sectional study of ophthalmology-based interventional clinical trials in ClinicalTrials.gov dating back to 1972 was conducted. χ2 tests were used to determine any potential associations between trial characteristics and trial completion. The Mann-Whitney U test was used to compare median time to publication between academic and industry-sponsored trials. RESULTS: Of 2926 included trials, 413 (14%) were discontinued early with only 19 of these studies being published. A total of 2027 (81%) of the 2513 completed trials were not published. A total of 277 419 participants were enrolled in unpublished, completed trials, whereas an estimated 20 843 participants were enrolled in trials that were never completed and never to led to publication. The odds of study discontinuation among industry-sponsored trials were 27% greater than government/academia-sponsored (National Institutes of Health, National Eye Institute, National Institutes of Health Clinical Center, U.S. and foreign university-based teaching hospitals) trials (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.03-1.57, p = 0.03). Furthermore, the odds of nonpublication among industry-sponsored trials were 55% more than those funded by government/academia (OR = 1.55, 95% CI 1.27-1.89, p < 0.0001). CONCLUSIONS: The nonpublication of many completed trials and of preliminary results of trials that are discontinued early dilutes the quality and decreases the comprehensive nature of the medical literature. This occurs in both industry and academia. Greater transparency through the publication of the entire spectrum of clinical trials' results as well as those that are terminated early could minimize publication bias and thus lead to a more robust medical literature.

Discontinuation and nonpublication of interventional clinical trials conducted in patients with mild cognitive impairment and Alzheimer's disease.

INTRODUCTION: Discontinuation and nonpublication of interventional clinical trials represents a waste of already scarce resources. We sought to identify the prevalence of discontinuation and nonpublication of interventional clinical trials conducted in patients afflicted by mild cognitive impairment and Alzheimer's disease. METHODS: We conducted a retrospective, cross-sectional study on mild cognitive impairment and Alzheimer's disease-based interventional clinical trials in ClinicalTrials.gov dating back to 1995. The analyzed data included trial phase, intervention type, enrollment, and funding sources. Fisher's exact and χ2 tests were used to determine any potential associations between trial characteristics and completion. RESULTS: A total of 744 studies were identified, of which 502 (67%) were industry-sponsored ones. A total of 127 (17%) were discontinued prematurely. Of the 617 completed trials, 450 (73%) were not published, representing approximately 66,655 participants who incurred the risks of trial participation without subsequently contributing to the medical literature. Similarly, there were 18,246 patients from unpublished, discontinued trials. Of the 744 trials examined, 247 publications from 167 trials could be identified via PubMed/MEDLINE and EMBASE searches. Most notably, the odds of nonpublication among industry-sponsored trials were more than 75% higher than those in studies funded by academia (odds ratio = 1.78; 95% confidence interval, 1.14-2.78; P = .01). Furthermore, industry-sponsored trials had a 50% greater odds of study discontinuation compared with trials funded by academia (odds ratio = 1.50; 95% confidence interval, 1.04-2.16; P = .03). DISCUSSION: The nonpublication of many trials and preliminary results of trials that are discontinued early dilutes the quality and decreases the comprehensive nature of the medical literature. This occurs in both industry and academia. Publication of inconclusive or negative results ensures that all research activities, regardless of outcome, contribute to global medical knowledge.

Sarcoid-like reaction in a patient with uveitis and underlying cancer.

PURPOSE: Sarcoidosis is a granulomatous disease of unknown etiology. Occasionally, triggering causes are identified, such as neoplasms, and they are termed sarcoid-like reactions, which may appear in any sarcoidotic target tissue. Choroidal metastases appear as part of widespread metastatic disease or as the first suggestion of neoplastic disease. They can also be a part of the differential diagnosis of a spectrum of inflammatory eye diseases. We present a case in which a lung carcinoma, pulmonary and eye sarcoid-like reactions, and choroidal metastasis take place in the same patient. CASE REPORT: A 60-year-old male with a past history of pulmonary sarcoidosis and associated anterior uveitis was diagnosed with a lung carcinoma with no regional lymph nodes extension, so that the resection surgery was performed without additional systemic treatment. At the same time, he complained of visual acuity loss and pain in his right eye. An intense ocular inflammatory reaction and a choroidal mass compatible with metastasis were identified. A vitrectomy with an accompanied histological exam of the lesion was deemed inconclusive. Ocular symptoms progressively worsened showing mass growth, and as a result, an enucleation was performed and the histological study subsequently revealed metastasis from his lung carcinoma. CONCLUSION: Sarcoid-like reactions may be due to incipient malignancies. Any diagnosis of sarcoidosis requires ruling out other diseases that can produce secondary sarcoid-like reactions. In addition, any choroidal mass suggestive of metastasis requires exclusion of metastatic disease even in the absence of clinical signs indicating tumor extension.

Moving forward in uveitis therapy: preclinical to phase II clinical trial drug development.

INTRODUCTION: Several advances have been made in the diagnostic approach and therapeutic management of patients with immune-mediated uveitis over the last few decades, which have to lead to an improvement in the visual prognosis of patients. However, the use of available therapies, including steroids and immunosuppressive drugs, is still associated with limited efficacy and potentially serious side effects. Consequently, efforts have been made to develop novel therapeutic alternatives including new molecules and innovative therapeutic approaches. AREAS COVERED: Herein, the authors provide an updated review of those drugs in the initial phases of evaluation for the treatment of immune-mediated uveitides as well as the latest evidence from basic research. EXPERT OPINION: Enhanced understanding of the pathogenic mechanisms leading to immune-mediated uveitis has led to the identification of new therapeutic targets and thus to the development of more specific drugs. In addition, considering that the eye is a semi-enclosed chamber and that local therapy has the benefit of sparing the rest of the body from potentially toxic exposure, several attempts of establishing direct ophthalmologic avenues for delivery of the established and emerging drugs have also been made. All these advances have been an unquestionable step forward in the challenging management of uveitis patients.

Treatment of severe non-infectious uveitis in high-risk conditions (Part 2): systemic infections; management and safety issues.

INTRODUCTION: Management of patients with severe immune-mediated uveitis requires the use of immunosuppressive (IS) drugs in selected cases. This may be particularly challenging in certain patients with associated conditions, which may increase the risk of side effects or modify guidelines for the use of such drugs. Chronic viral and mycobacterial infections in the setting of non-infectious uveitis create a number of diagnostic but also therapeutic dilemmas to clinicians because they can be exacerbated by IS therapies with detrimental effects. AREAS COVERED: In this review, we will focus on very specific chronic infections that can be affected by IS therapies: human immunodeficiency virus infection, chronic hepatitis virus infection and tuberculosis. The main aim of this review is to provide an updated and comprehensive practical guide for practitioners regarding the therapeutic decision-making and management of patients with non-infectious uveitis affected by the aforementioned infectious conditions. EXPERT OPINION: Clinicians should be aware of the risk of viral and mycobacterial reactivation of an underlying infection during IS therapy. However, most of these conditions do not represent an absolute contraindication if one were able to apply an appropriate prior screening and close monitoring of such therapy.

Treatment of severe non-infectious uveitis in high-risk conditions (Part I): pregnancy and malignancies, management and safety issues.

INTRODUCTION: Management of patients with severe immune-mediated uveitis requires the use of immunosuppressive drugs in selected cases. This may be especially challenging in certain patients with concomitant conditions, which could increase the risk of side effects or modify guidelines for the use of such drugs. Therapeutic decision-making and management may be of particular difficulty in pregnancy as well as in patients with associated malignancies unrelated to a specific ophthalmic inflammatory condition. AREAS COVERED: The main aim of this review is to provide an updated comprehensive practical guide for practitioners regarding the therapeutic decision-making and management of patients with severe immune-mediated uveitis in the context of pregnancy and malignancies. EXPERT OPINION: Management of patients with immune-mediated uveitis requiring immunosuppressive/immunomodulatory drugs might be particularly complicated by other conditions affecting their health and immune status. Clinicians should take into account such conditions, which might influence treatment response and the clinical outcome of these patients.

Comparing Prednisone and Methotrexate to Off-label Biologic Infliximab for Management of Ocular Uveitis: A Cost-minimization Analysis.

Background: Approximately 3.75% of cases of blindness in the United States are caused by uveitis. Incurred clinical costs and lost productivity related to vision loss in these cases totals $3.58 billion annually. Objective: To evaluate whether infliximab, a modern off-label biologic, is cost-effective for treating posterior uveitis and panuveitis compared to current standards of care, methotrexate and prednisone. Methods: A cost-effectiveness analysis using a Markov model to simulate a patient cohort with posterior uveitis or panuveitis. The model followed patients' therapy from the onset of posterior uveitis or panuveitis using the U.S. societal perspective. The lifetime model simulated health states that could lead to successful reversal of uveitis with standard or intensified treatment with prednisone, methotrexate, or infliximab. Probabilities, health utilities, and costs were included in the model based on findings from the literature. We conducted univariate sensitivity analyses and a Bayesian multivariate probablistic sensitivity analysis to estimate uncertainty in results. Outcomes were measured in terms of costs ($US, 2010) and effects (qualityadjusted life years; QALYs) discounted at 3% per year were estimated for each simulated treatment. An incremental cost-effectiveness ratio (ICER) for pairwise results was interpretted assuming a predetermined willingness-to-pay threshold of $100,000/QALY. Results: Average lifetime costs and QALYs for each drug were ($306.95; 15.80 QALYs) for prednisone, methotrexate ($36,232.24; 16.21 QALYs), and inflixmab ($74,762.63; 15.04 QALYs). Methotrexate was on average compared to prednisone, with an ICER of $86,901.16/QALY. Prednisone and methotrexate dominated infliximab. Sensitivity analyses suggested that the model was most sensitive to the utility for successful recovery from uveitis. The probabilistic sensitivity analysis returned results similar to the base case. Conclusion: This cost-effectiveness analysis suggests that despite advances in the use of biologics for treating sight-threatening posterior uveitis and panuveitis, infliximab had lower effectiveness and higher costs compared to both prednisone and methotrexate. As compared to prednisone, methotrexate was associated with increased costs and QALYs and was found to be a good value. Clinical trials of infliximab in the uveitis population are needed to reduce the uncertain estimates of inflixmab treatment success and the drug's cost-effectiveness.

Drug-induced uveitis.

INTRODUCTION: Drug-induced uveitis is a well described but often overlooked and/or misdiagnosed adverse reaction to medication. There are an increasing number of medications that have been related to the onset of intraocular inflammation. Identification of these inciting agents may decisively help the diagnostic algorithm involving new cases of uveitis. AREAS COVERED: This review intends to be an updated comprehensive, practical guide for practitioners regarding the main drugs that have been associated with uveitis. A classification proposed by Naranjo et al. in 1981 for establishing potential causality is applied examining possible mechanisms of action. A guide for clinicians about the rationale of these observations when dealing with patients with uveitis is provided. EXPERT OPINION: Several agents with different routes of administration (systemic, topical and/or intraocular) may cause intraocular inflammation. The mechanism behind ocular inflammation is frequently unknown. Clinicians should be aware of the potential drug effect to optimize diagnosis and management of such patients.

Localized bi-nasal macular edema in optic chiasmal syndrome.

A 28-year-old healthy male complaining of vision loss in his right eye was discovered to have localized bi-nasal macular edema in the presence of a pituitary adenoma. The presence of a junctional scotoma composed by a central scotoma in the right eye associated with superior temporal quadrantanopia in the fellow eye was seen. The pattern detected in the visual field suggested the presence of an expansive mass at the level of the optic chiasm. Optical coherence tomography findings also revealed subtle macular thickness beyond normal in the superior and nasal quadrants of both maculae. This report illustrates the importance of suspecting a pituitary adenoma in the light of uncharacteristic retinal alterations.

Combined therapy of cyclosporine A and mycophenolate mofetil for the treatment of birdshot retinochoroidopathy: a 12-month follow-up.

PURPOSE: To retrospectively report a 12-month follow up for combined therapy with systemic cyclosporine A (CSA) and mycophenolate mofetil (MM) in treatment of patients with birdshot retinochoroidopathy (BSRC). PARTICIPANTS: Ninety-eight eyes of patients who received CSA and MM for the treatment of BSRC were included in the study. METHODS: All patients were followed for at least five visits during the study, or until treatment failure, or loss of follow-up. Clinical data were analysed using a Student paired t-test, Wilcoxon signed-rank test, McNemar's test, and Kaplan -Meier survival curve. Side effects related to therapy were also recorded. Main outcome measures included best-corrected logarithm of the minimum angle of resolution visual acuity, vitreous inflammation, fluorescein angiography pathologic features, and electroretinogram recordings. RESULTS: Vitreous inflammation scores at baseline and at 1 year were statistically significantly reduced in both eyes (p<0.001; p=0.001). The presence of angiographic leakage at the 1-year follow-up was significantly reduced (p=0.004). However, the presence of cystoid macular oedema (p=0.32) and comparison of electroretinogram 30-Hz amplitude revealed no significant reduction between baseline and 1-year values for either eye (p=0.61, p=0.87); nonetheless, 30-Hz implicit times were statistically significantly shorter at the end of follow-up for both eyes (p<0.001, p=0.035). Thirty-one patients (67.4%) achieved inflammation control at the 1-year endpoint. Side effects were transient, and resolved after lowering or withholding IMT for a few weeks in the majority of patients. CONCLUSIONS: These results suggest that combined IMT with CSA and MM for BSRC is well tolerated and associated with long-term control of inflammation.

Systematic review of anti-tumor necrosis factor-alpha therapy for treatment of immune-mediated uveitis.

PURPOSE: To establish evidence-based recommendations regarding the use of anti-Tumor Necrosis Factor alpha (TNF-α) agents for managing uveitis patients. METHODS: Medline was searched via OVID (1950 - October Week 3, 2011) using a Cochrane highly sensitive search (phases 1 and 2). Additional literature searches were also conducted incuding the following databases: the Cochrane, LILACS and the TRIP Database. RESULTS: A total of 54 studies met all of the inclusion criteria and were included in this review. A different level of recommendation and evidence is assigned to each anti-TNF-α agent. The overall rate of reported side effects with anti-TNF-α agents for the treatment of uvetis which required discontinuation of therapy was 2.2% (26/1147 patients). CONCLUSION: Based on the evidence gathered, infliximab and adalimumab seem to be effective in the management of immune-mediated uveitis. Further randomized studies evaluating the efficacy of these agents are warranted. It is the most common cause of inflammatory eye disease, with an estimated prevalence of 115 cases per 100,000 persons. Endogenous or associated with a systemic disease, noninfectious uveitis accounts for approximately 75% of total cases comprising of a heterogeneous group of inflammatory conditions responsible for about 10% of legal blindness in developed nations. Endogenous uveitides are thought to have an autoimmune component mediated by T lymphocytes specific to intraocular antigens that have failed to successfully pass basic processes designed to maintain self-tolerance.

Use of bevacizumab for macular edema secondary to branch retinal vein occlusion: a systematic review.

INTRODUCTION: This systematic review assesses the effectiveness of intravitreal bevacizumab (IVB) versus a comparison group in the treatment of branch retinal vein occlusion (BRVO)-associated macular edema, and explores its effects on visual acuity (VA) and central macular thickness (CMT). METHODS: The authors searched the following databases: Medline (1950-October week 3, 2011), The Cochrane Library (Issue 10, 2011), EMBASE (up to 24 October 2011), and the TRIP Database (up to 24 October 2011), using no language or other limits. Trials that were included consisted of patients with BRVO-associated macular edema, those comparing a 1.25 mg IVB injection with a comparison group, those reporting both VA and CMT outcomes, and those having a minimum follow-up of 4 weeks. RESULTS: In the four trials comparing IVB with a comparison group, IVB was effective in improving VA and CMT values in the long-term (12 weeks) in patients with BRVO-associated macular edema. Furthermore, statistically significant improvements in VA in the short-term (4 weeks) could also be seen. DISCUSSION: Clinicians should use this review as an indicator that IVB is effective in improving VA and CMT values in the long-term in patients with BRVO-associated macular edema. It is important to note, however, that statistically significant improvements in VA in the short term could be seen. This review's main aim was to serve as an evidence base for potentially using other modalities, such as IVB, which seems to be reserved for certain cases.

Building information for systematic improvement of the prevention of hospital-acquired pressure ulcers with statistical process control charts and regression.

OBJECTIVES: To demonstrate complementary results of regression and statistical process control (SPC) chart analyses for hospital-acquired pressure ulcers (HAPUs), and identify possible links between changes and opportunities for improvement between hospital microsystems and macrosystems. METHODS: Ordinary least squares and panel data regression of retrospective hospital billing data, and SPC charts of prospective patient records for a US tertiary-care facility (2004-2007). A prospective cohort of hospital inpatients at risk for HAPUs was the study population. RESULTS: There were 337 HAPU incidences hospital wide among 43 844 inpatients. A probit regression model predicted the correlation of age, gender and length of stay on HAPU incidence (pseudo R(2)=0.096). Panel data analysis determined that for each additional day in the hospital, there was a 0.28% increase in the likelihood of HAPU incidence. A p-chart of HAPU incidence showed a mean incidence rate of 1.17% remaining in statistical control. A t-chart showed the average time between events for the last 25 HAPUs was 13.25 days. There was one 57-day period between two incidences during the observation period. A p-chart addressing Braden scale assessments showed that 40.5% of all patients were risk stratified for HAPUs upon admission. CONCLUSION: SPC charts complement standard regression analysis. SPC amplifies patient outcomes at the microsystem level and is useful for guiding quality improvement. Macrosystems should monitor effective quality improvement initiatives in microsystems and aid the spread of successful initiatives to other microsystems, followed by system-wide analysis with regression. Although HAPU incidence in this study is below the national mean, there is still room to improve HAPU incidence in this hospital setting since 0% incidence is theoretically achievable. Further assessment of pressure ulcer incidence could illustrate improvement in the quality of care and prevent HAPUs.

Adjunctive globe magnetic resonance imaging in the diagnosis of posterior scleritis.

OBJECTIVE: To report 4 cases of posterior scleritis with unusually unremarkable ultrasonography findings in which diagnosis was based on magnetic resonance imaging (MRI) examination. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Four patients. METHODS: Patients suffering from suspected posterior scleritis and previously misdiagnosed with a range of conditions after an unremarkable B-scan ultrasonography. A new and thorough review of systems, including MRI examination of the eye/orbit, was carried out. RESULTS: All included patients were diagnosed with posterior scleritis based on MRI findings. Systemic treatment with immunosuppressors (2 patients), antibiotics (1 patient), or no treatment (1 patient) got their inflammatory condition under control. CONCLUSIONS: MRI may play a potential role in the diagnosis of posterior scleritis particularly in those clinically suspicious cases with nondefinitive ultrasonography. Further studies on this matter are warranted.

Pharmacokinetics of triamcinolone acetonide for the treatment of macular edema.

INTRODUCTION: The use of intravitreal triamcinolone acetonide (TA) for the treatment of various types of macular edema has been widespread, particularly for the last decade. Currently, there is a scant amount of evidence-based literature evaluating the pharmacokinetic profile of TA despite clinical data showing the efficacy of intravitreal TA for multiple forms of macular edema. AREAS COVERED: This paper is an extensive review of human and experimental studies published on the pharmacokinetics of TA for the treatment of macular edema. The literature search was conducted via OVID, TRIP Database and EMBASE, up to April 2011. EXPERT OPINION: The pharmacokinetic profile of TA is unpredictable and the agent has a time-limited therapeutic action due to its relatively short half-life. This has led to the need for repeated injections. Future research should investigate the pharmacokinetic profiles of TA when administered intravitreally, as well as through alternate routes in more robust studies.