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The term uveitis refers to a group of inflammatory disorders affecting the uvea, the middle layer of the eye.
Before starting the treatment, a number of considerations should be taken into account (Table 1). Infectious causes and masquerade syndromesshould always be excluded before considering an immune-mediated mechanism, since therapeutic scheme is completely different.
Find out what factors, as well as inflammation, may be influencing the visual loss of the patient and their reversibility.
The most frequent cause of loss of visual acuity in patients with uveitis is macular edema (ME). The majority of patients with uveitis can modify significantly the course of their illness if they receive proper early treatment [10]. It is recommended to work in Multi-disciplinary Units to facilitate handling of the drugs used and early detection of side effects. Infectious causes and masquerade syndromes should always be excluded before considering an immune-mediated mechanism. A fourth point that we must always consider is a general attitude of zero tolerance to inflammation.
Figure: 1(A)Ultrasound biomicroscopy (UBM) in a patient with juvenile chronic arthritis (JIA) and chronic anterior uveitis. Figure: 1(D)Chronic uveitic macular edema with severe disruption of photoreceptor layer and coalescence of large cystic spaces. Specific entities with poor response to steroid immunotherapy (Behcet disease, Birdshot chorioretinopathy, serpiginouschoroidopathy…). A different therapeutic algorithm should be used depending on the type of uveitis and anatomical location. Most cases respond well to topical treatment and have an excellent prognosis if treatment is early and adequate. Treatment of AU is a medical emergency because delayed treatment may result in complications, sometimes irreversible, including anterior and posterior synechiae, secondary glaucoma, cataract orCME, that make the disease difficult to treat, and sometimes, with a very poor final visual function.
Treatment always starts with topical corticosteroids, usually eye drops during the daytime and ointment at bedtime.The steroid must have high anti-inflammatory activityand easy intraocular penetration. Treatment of AU also requires cycloplegic-mydriaticeye drops for control of pain caused by the ciliary muscle spasm and to prevent synechiae or break already present[16,17]. Although AU has usually good prognosis, there are cases with multiple flares annually, with great impact in quality of live due to pain, decreased vision and discomfort associated with pharmacological mydriasis. In AU B27-related, there is evidence that chronic administration of Sulfasalazine (SSZ) reduces the frequency and severity of recurrent episodes of uveitis [18-22].Although medication is generally well tolerated, it is necessary to take into account the risk of adverse events like skin reactions, blood dyscrasias or Stevens-Johnson syndrome. The incidence of AU in patients with AS treated with anti-TNF agents is less than in untreated patients, being lower in the group receiving infliximab or adalimumab than in the etanercept-treated group [23,24]. Methotrexate may also prevent recurrences of AAU in cases with a high number of relapses [25]. When inflammation affects the intermediate or posterior uvea, topical corticosteroids are not going to significantly change the course of the disease, so it will be necessary other forms of treatment to control uveitis. The classic treatment of IU is based on the four-step algorithm proposed by Kaplan[26], in which visual acuity is fundamental when starting treatment. If periocular administration is ineffective or insufficient, other forms of administration should be considered, such as intraocular or systemic treatment.Theintravitreal route is a very attractive form of administration because it provides a maximum concentration of corticosteroid at the posterior segment with minimal systemic absorption.
Systemic treatment is generally used, as first choice, in most cases of bilateral IU and, as a second option, in IU unresponsive or intolerant to local treatment.
Systemic corticosteroid treatment is usually used as first choice in the majority of the posterior uveitis, panuveitis and bilateral intermediate uveitis. Inpatients with particularly severe acute uveitis, for instance, Behcet disease, sympathetic uveitis or severe Vogt-Koyanagi-Harada syndrome, intravenous methylprednisolone should be considered.
In patients with severe uveitis in whom the dose of corticosteroids required to control the inflammation leads to unacceptable side effects or any other issues in (Table 2), an immunosuppressant agent should be added.
There is a subgroup of patients with severe sight-threatening uveitis that are refractory or intolerant to conventional immunosuppressive treatments. In current uveitis practice, biologics are usually used as third-line agents as rescue therapy for refractory cases in a step-up approach. The most usual approach is a step-up strategy, starting with corticosteroids and associating classical immunosuppressants and eventually biological in refractory cases. Another important issue regarding the use of anti-TNF- a is if this therapy could be discontinued in patients achieving sustained control of their uveitis. Gritz DC, Wong IG (2004) Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Noninfectious cystitis is irritation of the bladder that is not caused by a urinary tract infection. Causes Noninfectious cystitis is most common in women of childbearing years. This chapter focuses on two mucosal disease problems that cause significant pain and discomfort. Oral mucositis is a condition that is essentially a side effect of cancer therapy, namely, radiotherapy and chemotherapy. This condition is a painful and often dose-limiting complication of radiotherapy (RT) and combined chemoradiotherapy (CRT) to the head and neck. For chemotherapy-induced mucositis, the nonkeratinized mucosa of the oral cavity is typically affected (Figs. The frequency and severity of OM varies with different modalities of oncologic treatment regimens.9–11 As a general rule, OM lesions typically occur 1–2 weeks following chemotherapy or after radiotherapy doses greater than 30 Gy (gray, a unit of absorbed radiation). The type of antineoplastic treatment logically dictates the number and severity of patients who have OM. The burden of OM not only compromises the quality of life (QOL) of the patients but also significantly increases the cost of treatment and hospitalization due to associated pain and secondary infection management, diet and nutritional supplements, and gastrostomy tube placement. Oral mucositis is the clinical manifestation resulting from a complex sequence of events involving the activation of several intracellular signaling pathways with concomitant molecular changes. The initiation phase At the cellular and molecular level, immediately after administration of chemotherapy (CT) or radiation therapy (RT), the direct DNA damage caused by these treatment modalities leads to the production of reactive oxygen species (ROS), which results in death of cells in the basal layer and submucosal cells; collectively these events are referred to as the initiation phase. The primary damage response phase This second phase, the primary damage response phase, is characterized by the production of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-?), interleukin-6 (IL-6), and IL-1?, and activation of signaling pathways, such as the ceramide pathway, mediated in large part by the transcription factor nuclear factor kappa B (NF-?B). The signal amplification phase The signal amplifica­tion phase is characterized by positive feedback via NF?B with further upregulation of TNF-?, IL-6, IL-1?, cyclooxygenase-2 (COX-2), and other pro-inflammatory mediators, amplifying the damage caused to the tissues by increased inflammation and apoptosis. The ulceration phase The ulceration phase follows when there is clinically evident breakdown of the mucosa. The healing phase The healing phase is defined by restoration of the integrity of the mucosal tissues following termination of CT or RT treatment.
Figure 12.3 Summary of the main cellular and molecular events in the five-stage model of the pathogenesis of oral mucositis. Due to the relevance of NF-?B and pro-inflammatory cytokines in the pathogenesis of OM, a more detailed review of its role on this condition is warranted.20–22 It is important to highlight that NF?B is an important transcription factor responsible for the activation of several genes involved in inflammatory processes. The management of OM is largely palliative, consisting mainly of pain relief, nutritional support, and improved quality of life. All patients who are scheduled to undergo radiotherapy or chemotherapy regimes that have a high likelihood of OM development need to have a careful and detailed review of their oral hygiene practice.
Maintenance of oral hygiene is essential in patients with OM to prevent secondary infection and sepsis, to reduce pain, and to improve function.
Intake of regular diet and maintaining adequate nutrition become very difficult in OM patients. Because incipient dental disease can rapidly progress in a mouth that is not cleaned daily, correction of pre-existing oral conditions prior to the initiation of chemotherapy and subsequent aggressive mouth care reduce the incidence and severity of mucositis.45 Standard care should therefore include dental evaluation and correction of any periodontal disease before beginning chemotherapy. Chlorhexidine rinses at a 0.12% concentration have been widely used in dentistry as an antibacterial mouthrinse, especially in patients with periodontal disease who cannot clean their mouths effectively.
There may be a role for tricyclic antidepressants (TCAs) and fentanyl transdermal therapeutic system (FTTS) in the management of OM pain but further studies are needed.62,63 Chapter 4 covers the proper use of opioids for malignant and nonmalignant pain. Topical anesthetics such as 2% viscous lidocaine and “magic” mouthwash (a term that refers to different formulations used as mouthwash and consisting of a mixture of ingredients). Several agents or formulations have been used and studied as a protective mucosal barrier to aid in patient comfort during OM.66 Of these, sucralfate, Gelclair® (Helsinn Healthcare SA, Lugano, Switzerland), and Caphosol® (Cytogen Corporation, Princeton, NJ) are briefly discussed here. Sucralfate, a basic aluminum salt of sucrose sulphate has been used for both prevention and treatment for OM. This agent comes as an oral gel containing mainly polyvinylpyrrolidone and sodium hyaluronate that forms an adherent barrier over the oral mucosa. Endogenous or associated with a systemic disease, noninfectious uveitis accounts for approximately 75% of total cases comprising of a heterogeneous group of inflammatory conditions. Uveitis are responsiblefor about 10% of legal blindness in developed nations and more than 35% of patients with uveitis present significant visual loss in at least one eye [2-4].
Some infectious causes, such as toxoplasmosis, herpes, syphilis and tuberculosis could produce uveitis and, frequently, clinical signs are indistinguishable from those produced by the immune-mediated uveitis.
There can be comorbidities such as glaucoma, cataract, persistent vitreous opacities or macular ischemia that have their particular management.
When ME is chronic produces lesions in the retinal photoreceptors,which can potentiallybe irreversible [8,9]. UBM shows a cyclitic membrane that causes a detachment of ciliary body and chronic hypotony.
Due to its high and immediate efficacy, corticosteroids administered by different routes, are the drugs of choice in the induction of remission. Exceptions to this rule are chronic AU associated with JIA or Behcet's disease, which often requires systemic immunosuppressant associated with topical treatment [15]. The most widely used topical steroids are dexamethasone, betamethasone and prednisolone.The frequency of instillation varies with the intensity of the inflammatory reaction, but in general, the initial treatment should be aggressive for controlling the process as soon as possible.
Steroid withdrawal should not be very fast (not less than 4-6 weeks of treatment) that may predispose a rebound of inflammation [16].The most recurrent cases need a slower decrease in dose. The most common situation is CME associated with AU, but also in cases of therapeutic noncompliance or very severe flares with slow response to intensive topical treatment. We have already mentioned that AU associated with JIA or Behcet'sdisease often requires systemic immunosuppression associated with topical treatment[15]. The most widely used cycloplegic-mydriaticdrops,from highest to lowest potency and duration of action, are atropine, homatropine, cyclopentolate and tropicamide.Atropine is used in severe inflammation, with intense pain, because it is the one that best controls the pain.
Furthermore, recurrent inflammation and treatment with topical steroids can produce structural damage to the eye such as cataract, synechiae or glaucoma. Isolated episodes of uveitis not justify its use, it may be reasonable when there are three or more flares of AAU in the last year. Currently, many authors prefer early and aggressive treatment to preserve better visual acuity [27]. The risk is greater in patients with a history of hypertensive response to topical corticosteroids. Systemic treatment is described in the next section of this chapter in the therapeutic algorithm for posterior uveitis and panuveitis.

Ablation of the peripheral retina eliminates the source of inflammatory mediators and the stimulus for neovascularization[26,27]. In panuveitis or diffuse uveitis, inflammatory cells are spread roughly between the anterior chamber and vitreous cavity, and also there areinflammatory foci at the level of the retina, choroid or inflammation of the central retinal vessels. This treatment can be used in patients with unilateral or asymmetrical macular edemaevenin spite of long-term immunosuppression, unilateral flare-up of inflammation especially in Behcet’s disease, repeatedly where immunosuppressant is intolerable and as an adjunct to cataract, glaucoma or vitrectomy surgery in uveitis patients. The aim is to maintain quiescence at a lower steroid dosage.This combination has been used with success in various forms of uveitis.
However, there is ongoing arguments between uveitis specialists as to whether biologics should be considered as first-line therapy in certain cases (for instance, panuveitis in Behcet disease with macular involvement) following a top-down approach [48] (Figure 5).
Some studies show that this option may be possible, although most patients were on other immunomodulatory treatment at this time [49,50].
These treatments cause a painful, erythematous mucosa that transforms into even more painful ulcerations.5 The specific features of OM are provided next. It also develops in association with standard chemotherapy (CT) protocols used for cancer therapy as well as the high-dose conditioning regimens used with hematopoietic stem cell transplantation (HSCT).
It is now known that OM is not a condition exclusively affecting the epithelium, but rather involving all the cellular components of the mucosa. Pain is greatest during this phase, and secondary bacterial colonization of the ulcerated mucosa can further contribute by triggering more production of pro-inflammatory cytokines. NF-?B is activated in response to pathogens and pro-inflammatory cytokines and by radiotherapy and chemotherapeutic agents.
With regard to prevention of OM, several pharmacologic interventions have been reported as promising; unfortunately, the majority of studies conducted have not been well designed and are not randomized, placebo-controlled trials. In addition they need to understand how their diet must change and how proper nutrition might affect the course of their healing reaction.
Though the literature varies regarding the implementation of “basic oral hygiene,” most agree that tooth brushing is the best way to keep the mouth clean, preferable to oral sponges.40,41 Oral sponges or toothettes should only be used when the patient cannot tolerate a regular toothbrush. Patients should also receive instruction on mouth care and be encouraged to adhere to an aggressive oral hygiene regimen throughout the treatment period.
Chlorhexidine mouthrinses are used as part of oral decontamination in OM patients in some centers but would typically be discontinued with severe OM onset since the alcohol in the mouthwash would be too irritating.
The need for proper subjective and objective pain assessment in terms of function and need for medications has been reported.56,57 Management includes systemic analgesics (mainly opioids) and local palliative measures such as topical anesthetics, analgesics, and mucosal protective agents.
However, studies have not shown much benefit.67,68 The Cochrane review found no statistically significant differences, concluding that there is insufficient evidence to support or refute that sucralfate is more or less effective than placebo.
There is a wide spectrum of clinical forms of uveitis that are mainly classified according to criteria of anatomical location (anterior, intermediate, posterior orpanuveitis), laterality and clinical course (acute, recurrent or chronic). These data reveal the magnitude of the epidemiologic, diagnostic, and therapeutic problem posed -by the uveitis, as well as healthcare costs generated. It also iskept in mind that some lesions are irreversible (macular or optic atrophy, advanced glaucoma …) before starting an immunosuppressive treatment with iatrogenic potential risks in eyes without the possibility of visual recovery.
Are there other causes of poor vision, such as cataract, glaucoma or macular edema that could require specific treatment? However, in many cases, corticosteroids are not enough to sustained control of the inflammation in the long term.
The initial dose may be a drop every 1-3 hours, but there are cases where the inflammation is so severe that requires more frequent instillation (one drop every 15 to 30 minutes) or so slight that it can be controlled with more spaced doses.
Some patients require a minimum dose of topical corticosteroids for a long time to keep the eye without inflammation. Tropicamide, however, is used in milder uveitis or when inflammation has decreased to not interfere daytime vision. For these reasons, a treatment to reduce relapses should be very useful in this clinical setting[16,17]. In order to avoid this inconvenience, it has been developed slow-release devices that maintain effective levels of intravitreal steroids for extended periods of time, reducing the complications of multiple injections. The effect of this mode of treatment can be very rapid and uveitis usually responds in 48-72 h, then oral steroids with or without immunosuppressant can maintain inflammatory control. These are drugs specifically targeting pro-inflammatory cytokines involved in the immune response (TNF-a, IL-1, IL-2, etc).
In selected patients with fulminant uveitis (for instance, Behcet disease with macular involvement) a top-down approach starting with biological therapy as first-line therapy could be used.
The keratinized mucosa is generally spared with chemotherapy-induced OM, but may be affected following radiotherapy.
The World Health Organization (WHO) scale is preferred by many clinicians for its simplicity and ease of use (Table 12.1).
In this study, a total of 91% of patients developed OM of whom 66% had severe mucositis (Grade 3–4). Wherever possible, our recommendations are based on those put forth and endorsed by MASCC and the ISOO and are supplemented with Cochrane reviews whenever applicable. Maintenance of oral hygiene becomes extremely difficult, thus creating an ideal situation for opportunistic oral and potentially systemic infections. The typical approach is to have the pharmacist mix these agents together, dispense them with a 15-mL dosing cap and instruct the patient to keep this liquid cool (stored in the refrigerator at home). Both agents provided good short-term pain control but relief did not last for the full 24-hour assessment period in this study. Chronic uveitis is associated with a greater degree of structural damage and is responsible for a greater percentage of visual loss than acute forms.
So, both for diagnosis and, especially, for the proper treatment, close cooperation between ophthalmologists, rheumatologists and general practitioners are required in order to correctly classify thepattern of uveitis and associated comorbidities to establish the most appropriate therapeutic scheme. In other situations, the control of the inflammatory activity is not maintained when trying to reduce the dose of corticosteroids, or side effects of the treatment are not tolerable.
It is very important to use the right dose, since the use of a less aggressive regimen may lead to the erroneous conclusion that is a refractory uveitis[15]. The dose should be adjusted to the severity of inflammation and withdrawing completely by the end of steroid treatment. Biologicalcompounds potentially offer a safer profile and faster response than traditional immunosuppressive agents [46].
The helical design increases the surface area for drug release and stabilizes the device onto the sclera [35]. CyclosporineCyclosporine A placed in the deep sclera adjacent to the suprachoroidal space has been found to be effective in controlling uveitis in an equine recurrent uveitis model [42]. As mentioned, both conditions cause substantial pain, and patients with either condition need help with pain management. OM along with pharyngeal and other alimentary tract mucositic inflammation can lead to significant com­plications, including dysphagia, malnutrition, electrolyte imbalance, systemic infection, and even death. This scale measures clinical signs and symptoms as well as functional ability, mainly to eat and drink.
Hamsters that have received radiation and developed OM have an increased epithelial expression of TNF-? and IL-1? at day 15 postradiation.
Further randomized, placebo-controlled trials will have to establish the efficacy of this agent. Acute Anterior Uveitis (AAU) is the most prevalent form and usually requires only topical treatment with steroids and mydriatics. In these cases, an immunosuppressive treatment for the maintenance of remission is necessary (Table 2). To break synechiaealready present, we can associate phenylephrine eye drops in the office, but not as an outpatient basis due to the risks related to its use. So, intravitreal administration of steroids is a very effective treatment in managing endogenous uveitis, which allows significant decrease in systemic medication necessary for control of these patients and, therefore, their side effects. It can be performed following the recommendations of an expert panel (Table 3) [41].Initially this can be quite rapid, but the lower the current dose, the slower the necessary reduction. At present, there are injectable sustained-release dexamethasone implant (Ozurdex®) that can be inserted by the pars plana and have a better benefit-risk profile compared with other implants such as fluocinoloneacetonide(Retisert®) [44]. Among the biologics drugs, tumor necrosis factor-a (TNF-a) blockers (especially infliximab and adalimumab) have demonstrated promising results for the treatment of ocular inflammatory conditions in case series or retrospective reviews [47].At present, there is a lack of evidence-based recommendations regarding the use of these agents for managing uveitis. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.AbstractThe eye is a well-suited organ for local delivery of therapeutics to treat vitreous inflammation as well as other pathologic conditions that induce visual loss. Mitra, “Drug delivery to the retina: challenges and opportunities,” Expert Opinion on Biological Therapy, vol. If the patient is not already hospitalized, it is not uncommon for a severe OM to force hospitalization and untoward treatment modifications and interruptions. It is necessary to maintain immunosuppressant’s for long time, in order to achieve a stabilization of inflammatory parameters and avoid relapses and new flares. We must always take into account the risks associated with the procedure (endophthalmitis, retinal detachment, hemovitreous, ocular hypertension and cataracts) [38]. During the process of dose reduction, the patient should be carefully monitored to ensure that inflammatory parameters are under control and there is a sustained suppression of the inflammation. In addition, there is no approval for use in uveitis in technical sheet and, in clinical practice; these drugs are used as compassionate use. Several conditions are particularly challenging to treat and often require chronic courses of therapy. Bladder training exercises involve developing a schedule of times when you should try to urinate, while trying to delay urination at all other times. Where a specific oral ulcerative condition has a unique and evidence-based treatment method, this is also reviewed. They found that of the 109 patients with MM and 88 patients with NHL who were treated, severe OM occurred in 46% of MM patients and 42% of NHL patients respectively.
Compared with saline rinses, topical lidocaine is much more effective at reducing pain secondary to OM. Sulphasalazine and methotrexate have demonstrated a reduction in the number of flares and better control of inflammatory activity in cases of chronicity.
Multidisciplinary units (ophthalmologists with internists or rheumatologists) have been developed to achieve a close follow-up both at the level of efficacy and for early detection of side effects, allowing a better management and control of these therapies. If there is a relapse during dose reduction, a substantial increase of the dose is required to regain control (at least a doubling of current dose). Throughout this book, available drugs, dosages, safety issuesand experience of use in uveitis have been described in detail.(Figure 4) shows our therapeutic algorithm for immune-mediated posterior uveitis or panuveitis. The use of implantable intravitreal devices for drug delivery is an emerging field in the treatment of vitreous inflammation as well as other ophthalmologic diseases.
OM incidence rates, however, are at best rough estimates due to the lack of well designed prospective studies. Other patterns of uveitis with involvement of intermediate and posterior segments havea worse prognosis. There are unique challenges in the design of these devices which include implants, polymers, and micro- and nanoparticles.

This paper reviews current and investigational drug delivery systems for treating vitreous inflammation as well as other pathologic conditions that induce visual loss.
However, these exercises may also help relieve symptoms of urgency related to long-term (chronic) noninfectious cystitis. A recently published randomized double-blinded crossover study showed significant pain relief with topical morphine compared with placebo and the pain relief lasted for almost 2 hours with topical morphine solution.65 Additional information on topical anesthetics for oral pain can be found in Chapter 5.
Treatment consists in a phase of induction of remission using high-dose of systemic corticosteroids administered orally or by means of intravenous infusion.
The maintenance of systemic steroid treatment, even at low dose, are associated with important side-effects, such as dyspepsia, osteoporosis and risk of low-trauma fractures, weight gain, steroid myopathy, avascular bone necrosis, skin changes (acne, subepidermal atrophy, capillary fragility), inter-current infections, growth suppression in children, adrenocortical suppression and ocular side effects (cataract, ocular hypertension)[42]. The use of nonbiodegradable devices such as polyvinyl alcohol-ethylene vinyl acetate polymers and polysulfone capillary fibers, and biodegradable devices such as polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid, polycaprolactones, and polyanhydrides are reviewed.
Particulate Drug Delivery SystemsThe long-term drug delivery of small scale biodegradable devices has been recently investigated in experimental studies. Due to its multiple adverse effects, the dose of corticosteroids as maintenance therapy in uveitis should be the lowest possible and its withdrawal should always be attempted.
Clinically used implantable devices for therapeutic agents including ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and dexamethasone are described.
Although dexamethasone has a short half-life relative to triamcinolone, it is 20 and 5 times more potent than fluocinolone and triamcinolone, respectively (Table 3) [38].Ozurdex is placed intravitreally through the pars plana with an injector using a 22-gauge needle device. At this stage, the dose of corticosteroids is gradually reduced until withdrawal, and if necessary immunosuppressant’s are added. Finally, recently developed investigational particulate drug delivery systems in the form of liposomes, microspheres, and nanoparticles are examined.1. They are formed of a vesicular lipid bilayer separated by water or an aqueous buffer compartment [44].
Biological therapies, that are widely described in this book, are promising therapeutic options in refractory patients as a rescue therapy.
IntroductionThe eye is a model organ for the implantation of devices that provide long-lasting infusion of a therapeutic agent.
They can circumvent cell membrane barriers and protect drugs from metabolic or immune attack. However, there is clinical evidence of the use of these powerful drugs as first line therapy in selected cases (top-down approach). It is easily accessible for implantation of such a device and success of therapy is measurable objectively by direct visualization of the intraocular structures and by patient responsiveness. Since the phospholipid bilayers are naturally occurring, they are biocompatible and minimize toxicity and immunogenicity.Liposomes are colloidal particles made of phospholipids that encapsulate hydrophobic or hydrophilic therapeutic agents.
The treatment of posterior uveitis and vitreous inflammation usually involves a chronic course of therapy often over a period of years.
They often contain inner aqueous spaces where hydrophilic enzymes remain soluble and hydrophobic outer layers that allow passage through natural membrane barriers.Currently verteporfin (Visudyne, QLT Inc.
Blandford et al., “Intravitreal sustained-release ganciclovir,” Archives of Ophthalmology, vol.
Vancouver BC, Canada) is the only liposomal drug that is FDA approved for use in the eye for the treatment of predominantly classic wet AMD. Sub-Tenon’s and intravitreal steroid injections also can require frequent retreatment to adequately control disease.
Treatment with powerful systemic corticosteroid and immunomodulatory agents most often have poor vitreous penetration and can be associated with severe systemic side effects [1]. Implantable devices offer an alternative therapeutic approach that can circumvent many challenges of these other modes of therapy.The first implantable device for clinical use was developed in 1992 [2].
Vitrasert, a nonbiodegradable implant, delivers ganciclovir into the eye for the treatment of acquired-immunodeficiency-syndrome (AIDS)-related cytomegalovirus (CMV). More recently, there are serious investigations of biodegradable polymers that encapsulate particulate systems for long-lasting delivery of therapeutic nanoparticles which can be injected intravitreally.In this review, current and investigational drug delivery systems for treating vitreous inflammation are described.
Nonbiodegradable DevicesNonbiodegradable devices require surgical implantation and contain a drug reservoir within a permeable polymer membrane.
Although useful in some clinical settings, nonbiodegradable implants are not without limitations. Robinson, “Biodegradable implants for sustained drug release in the eye,” Pharmaceutical Research, vol.
Furthermore, these devices typically require removal and reimplantation of a second device once the drug has been completely released. The rate of drug release can be slowed by decreasing the surface area or increasing the thickness of the permeable membrane [3].
Schwartz, “Visual and anatomic outcomes associated with posterior segment complications after ganciclovir implant procedures in patients with AIDS and cytomegalovirus retinitis,” American Journal of Ophthalmology, vol. Ashton, “Subconjunctival sustained release 5-fluorouracil,” Investigative Ophthalmology and Visual Science, vol. Jaffe, “Intravitreal sustained-release dexamethasone device in the treatment of experimental uveitis,” Investigative Ophthalmology and Visual Science, vol. Martin et al., “Evaluation of a delivery system providing long-term release of cyclosporine,” Archives of Ophthalmology, vol.
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Kunou et al., “Biodegradable scleral implant for intravitreal controlled release of ganciclovir,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. Yasukawa et al., “Long-term sustained release of ganciclovir from biodegradable scleral implant for the treatment of cytomegalovirus retinitis,” Journal of Controlled Release, vol. Pitt, “Poly-e-caprolactone and its copolymers,” in Biodegradable Polymers as Drug Delivery Systems, M.
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Thompson, “Suppression of experimental proliferative vitreoretinopathy by sustained intraocular delivery of 5-FU,” International Ophthalmology, vol. Behar-Cohen, “Poly-epsilon-caprolactone intravitreous devices: an in vivo study,” Investigative Ophthalmology and Visual Science, vol. Mello-Filho et al., “Fabrication, implantation, elution, and retrieval of a steroid-loaded polycaprolactone subretinal implant,” Journal of Biomedical Materials Research Part A, vol. Lin, “Intravitreal implantation of the biodegradable cyclosporin A drug delivery system for experimental chronic uveitis,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. Wang, “FK506 in a biodegradable glycolide-co-clatide-co-caprolactone polymer for prolongation of corneal allograft survival,” Current Eye Research, vol.
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