Technological Advances In Drug Delivery To Treat .
Technological Advances in Drug Delivery to TreatNoninfectious Posterior Segment UveitisMeeting Diagnostic and Management ChallengesMichael A. Singer, MDABSTRACTWhen a patient presents with ocular inflammation, the hallmark of uveitis, the ophthalmologist is faced with a series of decisions. The first andmost critical challenge is to determine whether the condition is infectious or noninfectious, as that will indicate which treatment pathway is tobe followed. Once a patient has been diagnosed with noninfectious posterior uveitis, practitioners can choose between local and systemictreatments. If local therapy is selected, treatment may be topical or intravitreal: in either case, new medical options are available. Because of thecomplex nature of the condition and individual patient, it may be advisable in the course of either diagnosis or treatment for the ophthalmologistto consult the patient’s internist or, in some cases, rheumatologist. While effective management of uveitis presents challenges, today’s treatmentoptions are safer, more efficacious, and more streamlined than in the past and offer the promise of enduring remissions from symptoms.INTRODUCTIONUveitis is a group of inflammatory diseasesthat can lead to severe vision loss if leftuntreated. The incidence of uveitis is estimatedat between 17 and 52 cases per 100,000 peryear, with a prevalence of 38 to 714 cases per100,000.1 Uveitis may originate from diseasesoccurring locally in the eye or as an extensionof systemic inflammatory disease; 24% to55% of cases are considered idiopathic.Uveitis can involve inflammation not only of theuvea but also the lens, retina, optic nerve, andvitreous. Additionally, uveitis can be infectiousor noninfectious, acute or chronic, and canaffect the posterior segment, anterior segment,or both. Symptoms, which may include blurredvision, floaters, eye pain, redness, and lightsensitivity, vary according to the type andsite of inflammation.2 Early and appropriatetreatment of uveitis is critical: when incompletelytreated, uveitis’ characteristic recurrentinflammation impairs patients’ functioning andquality of life and can lead to vision loss.3Because uveitis can arise from any one ofmultiple causes and can vary in terms of theTARGET AUDIENCEThis educational activity is intended for ophthalmologistsand ophthalmologists in residency or fellowship training.LEARNING OBJECTIVESUpon completion of this activity, participants will be ableto:1. Define the screening, examination, laboratory analysisand imaging processes that drive accurate anddetailed uveitis diagnoses.2. Analyze the range of available and emerging treatmentoptions for noninfectious and posterior noninfectiousuveitis.3. Explain how to make the best match of treatment andpatient to decrease patient burden while optimizingtreatment outcomes.4. Review practice guidelines and options for adjustmentin cases where treatment is intolerable or ineffective.Supported by an unrestricted educational grant from ABBVIE.1428-TADD Abbvie.indd 1type and extent of tissue involvement,4 it oftenpresents as a diagnostic and therapeuticchallenge. Inflammatory, infectious, andcancerous diseases of the eye often presentwith similar ocular and neurological features.Diagnosis and treatment of complex,chronic, or refractory cases, therefore, oftenrequire knowledge that crosses betweeninternal medicine, infectious diseases,rheumatology, and immunology.5 Posterioruveitis, in particular, is usually treated by retinalspecialists, who are familiar with treatmentsand procedures for the posterior segment.Because of the multifaceted nature of uveitisdiagnosis and treatment, practitioners caring forpatients with uveitis face a series of challenges:arriving at an accurate diagnosis, treating theacute phase of the disease, and preventingsymptom recurrence. As a result, educatingpractitioners on the treatment and diagnosisof uveitis is critical. This article will provideguidance for negotiating the noninfectiousposterior uveitis pathway and discuss importanttechnological advances that have beenmade in posterior segment drug delivery.5. Use the knowledge of recent pivotal clinical trialoutcomes by comparing and differentiatiating threecritical technologies to manage posterior segmentnoninfectious uveitis: Ozurdex, Yutiq, and the CLS-TAinjection. Phase 3 clinical trial data will be reviewed toclose the educational gap.EDITORIAL BOARD / FACULTY ADVISORSSeenu Hariprasad, MDShui-Chin Lee Professor of Ophthalmology and VisualScience: Chief, Vitreoretinal Service: Director, ClinicalResearch: Director, Fellowship in Vitreoretinal Diseasesand Surgery: The University of Chicago Medicine &Biological SciencesMichael Singer, MDMedical Center Ophthalmology Associates, San Antonio,TXTom Albini, MDBascom Palmer Eye Institute, Miami, FLDIAGNOSTIC CHALLENGESDiagnosis is the first step in treating patientswith uveitis. Practitioners undertake aseries of steps and tests to determine if apatient has uveitis and, if so, which type.Classifying uveitisUveitis is classified in two ways, anatomicand etiologic. Anatomic classificationis the purview of the ophthalmologist,whereas etiologic classification may involveteamwork with other medical specialists.Anatomic classification: Ophthalmologistsconduct clinical examinations to classify potentialuveitis cases based on which tissues showinflammation. When inflammation appears inthe front of the eye, the condition is classifiedas anterior uveitis, which is also known as iritis.Inflammation in the back of the eye indicatesposterior uveitis; if inflammation occursthroughout the eye, it is diagnosed as panuveitis.6To rule out panuveitis, the examining physicianmust ensure that observed anterior uveitis doesnot have a posterior component and vice versa.Technological Advances in Drug Delivery to Treat Noninfectious PosteriorSegment Uveitis is jointly sponsored by Candeo Clinical/Science Communications, LLC, and the Universityof Florida College of Medicine. This publication isadministered by an independent editorial board andsupported by an unrestricted educational grant fromABBVIE.Copyright 2020 Candeo Clinical/Science Communications,LLC. All rights reserved. Neither the university of Floridanor Candeo Clinical/Science Communications, LLC,assumes any responsibility for injury or damage topersons or property arising from the use of information orideas contained in this publication.CME REVIEWERGibran Khurshid, MDAssociate Professor, Department of OphthalmologyUniversity of Florida College of MedicineTechnological Advances in Drug Delivery to Treat Noninfectious Posterior Segment Uveitis 112/16/20 3:00 PM
When uveitis occurs in the posterior segment,it commonly involves the retina and choroid. Inthe United States, posterior uveitis is the thirdmost common form of uveitis after anterior andpanuveitis, respectively. In patients 65 years ofage, however, posterior uveitis is more prevalentthan other forms of nonanterior inflammation,comprising 53% of nonanterior cases.According to the Standardization of UveitisNomenclature (SUN) classification, posterioruveitis includes focal, multifocal or diffusechoroiditis, chorioretinitis, retinochoroiditis,retinitis, and neuroretinitis.6 Compared withanterior uveitis, posterior uveitis carries a greatermorbidity and poorer prognosis.7 Visionthreatening complications in patients withnoninfectious posterior uveitis include macularedema, cataract, glaucoma, vitreous debris, andretinopathy. Macular edema, which was reportedin 8.3% of patients with noninfectious uveitisin a retrospective analysis of 334 patients fromthe Ocular Autoimmune Systemic InflammatoryInfectious Study (OASIS), is the most frequentlyencountered structural complication of uveitisthat results in central visual impairment,followed by epiretinal membrane andglaucoma (6.3% and 4.2%, respectively).8Etiologic classification: The origin of a patient’suveitis determines how it is best treated, anduveitis can stem from infectious or noninfectiouscauses. Because infectious and noninfectiousuveitis can share many common clinicalsymptoms and signs, etiological diagnosisis challenging. It is only when an infectiousetiology is ruled out that the practitioner’sfocus can move to treating inflammatoryrather than infective mechanisms.Clinical Examination:9 One of the most criticalsteps in properly diagnosing and treatinguveitis is the clinical examination. Clinicalsymptoms of anterior uveitis are a red, painful eyeaccompanied by anterior chamber cell and flare,posterior synechiae, and keratic precipitates.Posterior uveitis causes worsened vision andvisual field changes, chorioretinal lesions, retinalwhitening, and vascular sheathing. Inflammationin the vitreous may impede visualization of theposterior segment, in which case a PCR assay onan anterior chamber specimen may be required.10Inflammation in the posterior segment mayinvolve adjacent structures such as theretina, vitreous, optic nerve head, or retinalvessels, along with choroidal inflammation.11The examining physician may, therefore, findit helpful to keep the following questions inmind throughout the investigative process:Is this inflammation choroiditis, retinitis, orretinochoroiditis? Are the optic nerve head orthe retinal vessels involved? Do the clinicalfeatures suggest any known infective or noninfective entity? Are there associated anteriorsegment inflammation, vitritis, or complications?Is the condition associated with other systemicfeatures? Is it recurrent? If so, how has itresponded to previous therapy? Finally, is itassociated with an immunocompromised state?11Technological Advances in Drug Delivery to Treat NoninfectiousPosterior Segment UveitisSTATEMENT OF NEED#1 Identified Need: Need for accurate uveitisdiagnoses with details regarding cause, site, onset,duration, and courseDesired Result: Rapid, accurate, and reproduciblediagnosisLearning Objective: Define the screening, examination,and laboratory analysis process that drives accurate anddetailed uveitis diagnoses#2 Identified Need: Selection of uveitis treatmentbased on cause and typeDesired Result: Selection of treatment options thatare eff ective, safe, and appropriate for each type ofuveitis patientLearning Objective: Analyze the range of available andemerging treatment options for noninfectious andposterior noninfectious uveitis#3 Identified Need: Create “best-match” treatment tominimize patient burdenDesired Result: Determine treatment that will bestminimize patient burden and optimize outcomesLearning Objective: Understand patient needs inselecting treatment to minimize patient burden whileoptimizing treatment outcomes#4 Identified Need: Need for vigilant managementto maximize chances of treatment success and reduceincidence of treatment-related adverse eventsDesired Result: Improved health outcomes(inflammation management, vision restoration,alleviation of pain) with reduced risk and burden topatientLearning Objective: To review practice guidelines andoptions for adjustment in cases where treatment isintolerable or ineffective#5 Identified Need: Compare and differentiate threenew technologies to manage posterior segmentnoninfectious uveitisDesired Result: Improved health outcomes (inflammationmanagement, vision restoration, alleviation of pain) withreduced risk and burden to patientLearning Objective: Knowledge of recent pivotalclinical trial outcomes for new technologies to treatnoninfectious posterior uveitisOFF-LABEL USE STATEMENTThis work may discuss off-label uses of medications.GENERAL INFORMATIONThis CME activity is sponsored by the Universityof Florida College of Medicine and is supported byan unrestricted educational grant from ABBVIE.The University of Florida College of Medicine designatesthis enduring material for a maximum of 1 AMA PRACategory 1 Credit . There is no fee to participate in thisactivity. In order to receive CME credit, participantsshould read the report, and then take the posttest.A score of 80% is required to qualify for CME credit.Estimated time to complete the activity is 60 minutes. Oncompletion, take the test online at https://cme.ufl. edu/online-cme/tadd/System requirements for this activity are:For PC users:Windows 2000, XP, 2003 Server, or Vista; Internet Explorer 6.0 or newer, or Mozilla Firefox 2.0 or newer(JavaScriptTM and JavaTM enabled).For Mac users:Mac OS X 10.4 (Tiger ) or newer; SafariTM 3.0 or newer,Mozilla Firefox 2.0 or newer; (JavaScript and Java enabled).DATE OF ORIGINAL RELEASEJanuary 2021. Approved for a period of 12 months.History: A detailed medical history will helpto determine whether the patient may have2 Technological Advances in Drug Delivery to Treat Noninfectious Posterior Segment Uveitis1428-TADD Abbvie.indd 2ACCREDITATION STATEMENTThis activity has been planned and implemented inaccordance with the accreditation requirements andpolicies of the Accreditation Council for ContinuingMedical Education (ACCME) through the jointprovidership of the University of Florida College ofMedicine and Candeo Clinical/ScienceCommunications, LLC. The University of FloridaCollege of Medicine is accredited by the ACCME toprovide continuing medical education forphysicians.CREDIT DESIGNATION STATEMENTThe University of Florida College of Medicinedesignates this enduring material for a maximum of1 AMA PRA Category 1 Credit . Physicians shouldclaim only the credit commensurate with the extent oftheir participation in the activity.FACULTY AND DISCLOSURE STATEMENTSNo one else in a position to control content hasany financial relationships to disclose.CME ADVISORY COMMITTEE DISCLOSUREConflict of interest information for the CMEAdvisory Committee members can be found on thefollowing website:https://cme.ufl.edu/disclosure/Seenu Hariprasad, MD Shui-Chin Lee Professor ofOphthalmology and Visual Science: Chief,Vitreoretinal Service: Director, Clinical Research:Director, Fellowship in Vitreoretinal Diseases andSurgery: The University of Chicago Medicine &Biological Sciences. Dr. Hariprasad is a consultant forAllergan, Novartis, EyePoint Pharmaceuticals andAlimera Sciences. He is on the Speaker’s Bureau forAllergan, Novartis, Alimera Sciences, EyePointPharmaceuticals, Spark Therapeutics andRegeneron Pharmaceuticals.Michael Singer, MD Medical CenterOphthalmology Associates, San Antonio, TX. Dr.Singer received Grant/Research support fromAllergan, Aerie, Genentech, Regeneron, Eyepoint,Optos, Kodiak and Senju. He is a consultant forAllergan, Aerie, EyePoint Pharmaceuticals,Genentech, Regenreon. Dr. Singer serves on theSpeaker’s Bureau for Allergan, EyePointPharmaceuticals, Genentech, Regeneron, and SparkTherapeutics and is a Stock Shareholder inNancoscope and Inflammasome.Tom Albini, MD Bascom Palmer Eye Institute,Miami, FL. Dr. Albini is a consultant for AllegroOpthalmiocs, Allergan, Beaver, Visitec, AdverumBiotechnologies, EyePoint Pharmaceuticals,Novartis, Santen Pharmaceuticals, Genentech,Valeant Pharmaceuticals, Notal Vision, JanssenBiotech, Regenex Bio and Clearside Biomedical.Gibran Khurshid, MD, is an associate professor inthe department of ophthalmology at the Universityof Florida College of Medicine. He states that in thepast 12 months, he has not had a financialrelationship with any commercial organization thatproduces, markets, resells, or distributes healthcaregoods or services consumed by or used on patientsrelevant to this manuscript.DISCLAIMERParticipants have an implied responsibility to usethe newly acquired information to enhance patientoutcomes and professional development. Theinformation presented in this activity is not meantto serve as a guideline for patient care. Procedures,medications, and other courses of diagnosis andtreatment discussed or suggested in this activityshould not be used by clinicians without evaluationof their patients’conditions and possiblecontraindications or dangers in use, applicablemanufacturer’s product information, andcomparison with recommendations of otherauthorities.COMMERCIAL SUPPORTERSThis activity is supported by an unrestrictededucational grant from ABBVIE.To obtain CME credit for this activity, go to https://cme.ufl.edu/online-cme/tadd/12/16/20 3:00 PM
an infectious condition. Ophthalmologistsshould ask about any prior inflammatoryevents or infections in the eye, such as herpesor varicella, as well as any known infectiousdiseases, such as tuberculosis or Lyme disease.Practitioners should ask about high-risksexual behavior, which could put the patient atrisk for syphilis or human immunodeficiencyvirus. Additionally, exposure to pets or otheranimals might suggest toxoplasmosis ortoxocaraiasis. In a 2015 study by Bajwa et al,toxoplasmosis was the most common causeof posterior uveitis.12 Practitioners should askabout recent illnesses or hospitalizations. Lymedisease, syphilis, tuberculosis, and sarcoidosisall have significant systemic ramificationsthat can contribute to uveitis. In adolescentsand adult patients, it is very important toexclude syphilis. 3 The patient’s internist maybe able to provide important backgroundinformation that will help in the diagnosis.Age range: Underlying conditions affectinguveitis etiologies or severity may appear more orless commonly depending on patient age. Forinstance, younger patients are more likely to havejuvenile rheumatoid arthritis, Behçet’s disease, orankylosing spondylitis, whereas in older patients,it is important to rule out lymphoma or syphilis.14Laboratory tests: Additionally, ophthalmologistscan order a battery of laboratory tests todetermine whether uveitis is caused by bacteria,virus, fungus, or another source. A thoroughworkup for uveitis would include a completeblood count as well as sedimentation rate. Otherblood tests might include rheumatoid factor,antinuclear antibody to rule out rheumatoidarthritis, and angiotensin-converting enzymefor sarcoidosis.14 In younger patients with backpain, it would be helpful to test for HLA-B27or a simple lumbo-sacral Xray to rule outankylosing spondylitis. Brewerton ref If thepatient has cats or dogs or has been exposedto other animals, the practitioner should testfor toxoplasmosis or toxocaraiasis. A skin test,blood interferon-gamma release assay, orchest X-ray should be conducted to rule outtuberculosis.14 Additionally, imaging techniquessuch as fundus fluorescein angiography(FFA), indocyanine green angiography (ICG),ultrasonography (USG), and optical coherencetomography (OCT) may be used to shed light onthe presence or nature of infection in the eye.11Idiopathic uveitis: As has been noted, up to halfof uveitis cases will, after careful workup, beclassified as idiopathic. However, it has beensuggested that some “idiopathic” cases mayreflect incomplete patient medical history orimperfect laboratory testing and may actually beuveitis secondary to sarcoidosis, tubulointerstitialnephritis, or ankylosing spondylitis.21,22TREATMENT CHALLENGESThe first goal of treatment is to suppressthe inflammation and improve the patient’ssymptoms quickly. The second goalis to prevent recurrences and therebyprevent the damage to optical tissues thatcan lead to permanent vision loss.Supported by an unrestricted educational grant from ABBVIE.1428-TADD Abbvie.indd 3Local or systemic treatment: In decidingwhether to use local or systemic treatment, itis important to consider whether the uveitisis unilateral, bilateral, or unilateral alternating.In unilateral alternating disease, either eyemay be affected by an attack, but only oneeye is affected at a time, and the attacksare recurrent in nature. Local treatment ismore likely to be used in unilateral uveitis.Topical steroids are typically the initial treatmentfor noninfectious uveitis. Topical steroids havethe advantage of being relatively benign and easyto discontinue. They also don’t penetrate veryfar past the anterior chamber, which means thatthey will not make an infectious disease worse.Because of their limited penetration, however,steroids have less efficacy in the posteri
3. Explain how to make the best match of treatment and patient to decrease patient burden while optimizing treatment outcomes. 4. Review practice guidelines and options for adjustment in cases where treatment is intolerable or ine ective. 5. Use the knowledge of recent pivotal clinical
2. Dissolution controlled drug delivery systems 3. Encapsulated drug delivery systems 4. Diffusion controlled drug delivery systems 5. Matrix type Among these class 1 contains new drug delivery systems as transdermal delivery, intra uterine delivery, ocular inserts, and sub dermal implants [4-6]. The
advances in agronomy adv anat em advances in anatomy embryology and cell biology adv anat pa advances in anatomic pathology . advances in organometallic chemistry adv parasit advances in parasitology adv physics advances in physics adv physl e advances in physiology education adv poly t advances in polymer technology
Free drug (a) Tumor Drug-loaded NPs (b) F : Schematic contrast of drug biodistribution a er injection of free drug (a) and drug-loaded NPs (b). self-assembly), targeted drug delivery processes, and the current state of NP computational modeling. Directions for future research are also discussed. 2. Self-Assembled Nanoparticles as Delivery Vehicles
TDD market is very optimistic.Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. This review emphasizes the three generations of transdermal drug delivery which start a new era of delivery of drug.
member requests a refill of the drug, at which time the member will receive a 60-day supply of the drug. If the Food and Drug Administration deems a drug on our formulary to be unsafe or the drug’s manufacturer removes the drug from the market, we will immediately remove the drug from our formulary and provide notice to members who take the drug.
Drug delivery system, as one of the chemotherapeutic treatments has received enorrmous attention from researchers. This thesis is to develop amphiphilic diblock copolymer protected nanoparticles loaded with anti-cancer drug, with small size and high drug loading, to achieve selective drug delivery using EPR effect.
The disadvantages of drug targeting16 1. Rapid drug elimination from the body results in high dose frequency. 2. The carrier of the targeted drug delivery system may result in the immune response. 3. The drug delivery system is not localized at the tumor tissue for sufficient time. 4. The diffusion and redistribution of released drugs. 5.
Transdermal drug delivery system (TDDS) established itself as an integral part of novel drug delivery system. Transdermal drug delivery systems (TDDS), also known as “patches,” are dosage forms designed to deli
