The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management

doi:10.1016/j.survophthal.2015.07.001

Survey of Ophthalmology

Volume 61, Issue 1, January–February 2016, Pages 1-17

https://doi.org/10.1016/j.survophthal.2015.07.001 Get rights and content

Abstract

Ocular inflammatory disease is a leading cause of vision loss worldwide. Uveitis encompasses a wide spectrum of pathology, both with respect to its etiology and the anatomic location within the eye. Inflammation can be confined to the eye and may also be seen systemically. The cornerstone of management of ocular inflammatory disease historically has been corticosteroids, which are invaluable in the immediate control of inflammation; however, corticosteroids are inappropriate for long-term use as they are associated with a wide array of toxic side effects. As we continue to learn more about the various etiologies and elucidate the basic science pathways and mechanisms of action that cause intraocular inflammation, new therapeutic approaches have evolved. They include employment of immunomodulatory agents (corticosteroid-sparing therapies) that have expanded our treatment options for these vision-threatening diseases. These pharmacologics provide therapy for ocular and systemic inflammation in an individualized, patient-tailored, stepladder approach with the ultimate goal of durable, corticosteroid-free remission. We review the preferred practice patterns of a tertiary care center specializing in ocular inflammatory disease.

Section snippets

Global impact on vision

Intraocular inflammatory disorders encompass a broad spectrum of disease in which the eye or its various parts may be attacked by the immune system, leading to severe visual impairment. Uveitis is the third leading cause of worldwide blindness and currently accounts for approximately 10% of preventable vision loss in the US and up to 15% worldwide.10, 21, 24, 47, 63 In the US alone, uveitis has an estimated prevalence of about 38 cases per 100,000 and an incidence of 15 cases per 100,000.²⁴ An

Uveitis etiology: Noninfectious and infectious

Several uveitis classifications schemes exist. They vary based on the anatomic location of inflammation, clinical course, etiology, and histopathology. The Standardization of Uveitis Nomenclature (SUN) Working Group developed an anatomic classification system in 2005 that arguably serves as the most widely used today.²⁸ The following are types of uveitis based on anatomic location (Table 1).

(1)
Anterior uveitis
(2)
Intermediate uveitis
(3)
Posterior uveitis
(4)
Panuveitis

Anterior uveitis has the highest

Medical management of uveitis

Therapy for uveitis may appropriately involve medical or surgical intervention. The preferred practice pattern that we advocate in the care of patients with uveitis is aimed at cure. The first stage in the successful pursuit of cure is the induction of durable, corticosteroid-free remission—and doing whatever it takes to accomplish that goal—whereas at the same time doing no harm, not producing quality of life-altering side effects or complications from the strategies used in that quest for

The stepladder approach

In an effort to prevent irreversible structural damage and blindness, the guiding principle of management of patients with uveitis is diagnostic and therapeutic vigor. This means early diagnosis, referral to a uveitis specialist, and therapeutic aggressiveness using a stepladder algorithmic approach, which is both corticosteroid-sparing and titrated to the severity of intraocular inflammation¹⁶ (Fig. 1).

The cornerstone of medical therapy should include topical, regional and systemic

Diagnostic procedures

An aqueous sample may be obtained for diagnostic purposes. A tuberculin or 3 mL syringe is attached to a sterile 30-gauge needle that is then advanced into the anterior chamber through the temporal limbus or clear cornea parallel to the iris plane avoiding the iris and lens. 0.1–0.2 cm³ of aqueous is aspirated. The needle is removed and topical antibiotic instilled. The aqueous sample may be sent for microbiologic, histological evaluation, or polymerase chain reaction evaluation. Potential side

Emerging therapies

Transscleral iontophoresis is an active method of drug delivery that uses a small electrical current to enhance diffusion of drug molecules across an intact sclera. As a noninvasive and well-tolerated method, iontophoresis has the potential to replace systemic administration and repeated intravitreal injections for posterior segment diseases. Eyegate (Optis Group, Paris, France) and OcuPhor (IOMED, Salt Lake City, USA) are the main ophthalmic iontophoresis systems under investigation.

The

Conclusion

The continuing advances in understanding the mechanism of action of drugs, the underlying pathogenesis of uveitic entities, and the uveitic cascade are the keys to better understanding this devastating eye disease with vision threatening potential. The approach of delivering targeted therapy to intervene at these crucial points to achieve corticosteroid-free durable remission, providing individualized care to our patients, and thus enhancing their quality of life is our goal.

The use of the

Addendum

Drug tables.2, 3, 5, 11, 12, 13, 16, 18, 22, 26, 27, 29, 33, 34, 35, 36, 37, 38, 41, 42, 46, 50, 51, 55, 56, 60, 61, 62, 66

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Cited by (125)

The Humira in Ocular Inflammations Taper (HOT) Study
2024, American Journal of Ophthalmology
To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission.
Retrospective study.
In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering.
Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04).
When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable.
Preparation of polycaprolactone and polymethacrylate nanofibers for controlled ocular delivery of ketorolac tromethamine: Pharmacokinetic study in Rabbit's Eye
2024, European Journal of Pharmaceutical Sciences
Ophthalmitis is an inflammation of the eye triggered by various conditions including diseases, allergy, trauma, or surgery. Management of this condition usually includes administration of topical anti-inflammatory eye drops such as nonsteroidal anti-inflammatory drugs. To overcome the challenges of conventional eye drops such as frequent administration and low intraocular bioavailability, nanofibrous inserts of Ketorolac tromethamine (KET) were developed in this study. Polycaprolactone and polymethacrylate containing KET were electrospun to prepare biocompatible and biodegradable nanofibers. The inserts were studied for morphology, drug-polymer interaction, physicochemical properties, cell viability, in vitro drug release study and pharmacokinetic study in rabbit's eye. Uniform nanofibers with mean diameters < 350 nm were developed. Suitable mechanical properties with tensile strength up to 2.8 MPa indicated high strength and flexibility of inserts. Nanofibers exhibited controlled drug release for up to 140 h at a concentration more than 50 μg/ml in tears without causing any damage or irritation to the eye. Formulations indicated enhanced pharmacokinetics with 6- to 8-times higher Area Under the Curve (AUC_0–144) compared to KET eye drop. Acceptable cell viability confirmed the safety of inserts. Due to the fact that this preservative-free polymer insert can obtain therapeutic concentration in the tear film without fluctuation, it can be a suitable alternative for the treatment of intraocular inflammations with less complications, easier use, and even higher intraocular penetration.
Design, optimization and pharmacokinetic evaluation of PLGA phosphatidylcholine hybrid nanoparticles of triamcinolone acetonide loaded in situ gel for topical ocular delivery
2023, International Journal of Pharmaceutics
Posterior uveitis (PU), which often has an autoimmune origin, can be treated effectively with synthetic glucocorticoid triamcinolone acetonide (TAA). Due to the limitations of topical TAA administration reaching the posterior segment of the eye, the drug is injected directly into the eye through an intravitreal injection. In this study, we prepared TAA loaded poly(lactic-co-glycolic acid) phosphatidylcholine hybrid nanoparticles (TAA-PLHNPs) using the principles of design of experiments (DoE) for topical ocular administration. The mean particle size (nm) and drug loading efficiency (LE%) for the optimized formulations were 163 ± 2.8 nm and 39 ± 1.9%, respectively. The TAA-PLHNPs were then loaded into the dual responsive in situ gel that we reported in our previous work. In vitro assessments were done to show that the formulations are safe for ocular administration. Finally, in vivo ocular pharmacokinetic studies were performed to compare pharmacokinetic parameters of TAA-PLHNPs and TAA-PLHNPs loaded in situ gel with each other and with the previously reported conventional formulation of TAA (aqueous suspension of TAA with 20% hydroxypropyl β-cyclodextrin (TAA-HP-β-CD-Susp)). TAA-PLHNPs loaded dual responsive in situ gel (TAA-PLHNP-ISG) achieved higher concentrations of TAA in the vitreous humor (C_max of 946.53 ng/mL) and sustained (MRT_0–∞ of 16.26 h) the drug concentrations for longer period of time compared to aqueous suspension of TAA-PLHNPs (TAA-PLHNP-Susp) and TAA-HP-β-CD-Susp.
Secondhand smoke exposure and ocular health: A systematic review
2023, Survey of Ophthalmology
The toxicology of secondhand smoke (SHS), along with the harm of its exposure to human health, has been generally acknowledged; however, specific evidence is lacking on the association between SHS exposure and ocular health. In this systematic review (PROSPERO registration number: CRD42022247992), we included 55 original articles published by 12 May 2023, which dealt with SHS exposure and ocular disorders, such as eye irritation, conjunctivitis, dry eye diseases, uveitis, myopia, astigmatism, contact lens discomfort, age-related macular degeneration, glaucoma, and thyroid eye disease that addressed the ocular neurovascular structures of the macular, retinal nerve fiber layer, choroid, and corneal biomechanical parameters. We found compelling correlational evidence for eye irritation, conjunctivitis, and dry eye symptoms—supporting that SHS exposure was positively associated with inflammatory and allergic changes in the eyes. Yet, evidence about the associations between SHS exposure and other ocular disorders, structures, and parameters is still limited or controversial. Given the limitations of existing literature, more investigations with high quality and rigorous design are warranted to elucidate the potentially harmful effects of SHS exposure on ocular health.
Vision Outcomes of Long-Term Immunomodulatory and Steroid Therapy in Sympathetic Ophthalmia
2023, American Journal of Ophthalmology
To compare vision acuity outcomes of long-term steroid therapy compared with immunomodulatory therapy for treatment of sympathetic ophthalmia.
Single-center, retrospective, comparative clinical study.
Patients with sympathetic ophthalmia treated from March 2005 to October 2022 with at least 1 year of follow-up were included. Visual acuity outcomes were compared by steroid and immunomodulatory treatment modality.
Thirty-five patients with sympathetic ophthalmia were included in the study, with follow-up ranging from 1 to 17 years. Higher rates of vision loss correlated with longer periods of active uveitis and steroid treatment. Lower rates of vision loss correlated with longer periods of uveitis remission on immunomodulatory therapy alone and drug-free remission. Treatment with alkylating agents or combination therapy with an antimetabolite, a biologic-response modifier, and cyclosporine are more likely to result in sympathetic ophthalmia remission.
Immunomodulatory therapy leads to superior vision outcomes in cases of steroid-resistant or recurrent sympathetic ophthalmia. Steroid therapy may be useful for acute or recalcitrant sympathetic uveitis but is insufficient for long-term inflammatory control.
This manuscript describes a retrospective analysis of vision outcomes in patients with sympathetic ophthalmia. Results indicate that long-term immunomodulatory therapy is associated with better vision outcomes than long-term steroid therapy for sympathetic ophthalmia treatment.
Dissolvable hybrid microneedle patch for efficient delivery of curcumin to reduce intraocular inflammation
2023, International Journal of Pharmaceutics
Intraocular inflammation seriously impairs vision, and the effectiveness of intraocular drug delivery is hampered by various physiological barriers, such as the corneal barrier. In this paper, we present a simple approach to fabricating a dissolvable hybrid microneedles (MNs) patch for the efficient delivery of curcumin to treat intraocular inflammatory disorders. Water-insoluble curcumin was first encapsulated into polymeric micelles with high anti-inflammatory capacities, and then were combined with hyaluronic acid (HA) to create a dissolvable hybrid MNs patch using a simple micromolding method. Curcumin was amorphously dispersed within the MNs patch as indicated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analyses. According to an in vitro drug release study, the proposed MNs patch provided sustainable drug release over 8 h. Following its in vivo topical application, the MNs patch demonstrated an extended pre-corneal retention time over 3.5 h and exhibited great ocular biocompatibility. Additionally, such MNs patch could reversibly penetrate the corneal epithelium, generating an array of microchannels on the corneal surface, thereby increasing ocular bioavailability. Of greater significance, the use of MNs patch demonstrated the improved therapeutic effectiveness in treating endotoxin-induced uveitis (EIU) in a rabbit model compared to curcumin eye drops via a significant reduction in the infiltration of inflammatory cells such as CD45⁺ leukocytes and CD68⁺ macrophages. Overall, the topical application of the MNs patch as an efficient ocular drug delivery system could potentially serve as a promising approach for treating different types of intraocular disorders.

View all citing articles on Scopus

: The protocols presented in the above tables (Table 8, specifically) are specific to the practice of Dr. C. Stephen Foster and are not intended to suggest that they represent protocols in common usage.

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Major reviewThe Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management

Abstract

Section snippets

Global impact on vision

Uveitis etiology: Noninfectious and infectious

Medical management of uveitis

The stepladder approach

Diagnostic procedures

Emerging therapies

Conclusion

Addendum

J Cataract Refract Surg

Ophthalmology

Ophthalmology

Surv Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Am J Ophthalmol

Surv Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

Ophthalmology

Trends Immunol

Ophthalmology

Basic and Clinical Science Course: Section 9

Using interleukin 10 to interleukin 6 ratio to distinguish primary intraocular lymphoma and uveitis

Invest Ophthalmol Vis Sci

Intraocular inflammatory disorders update

Retin Physician

Intravitreal bevacizumab in refractory uveitic macular edema: one-year follow-up

Eur J Ophthalmol

High-dose intravenous corticosteroids for ocular inflammatory diseases

Ocul Immunol Inflamm

Mycophenolate mofetil for ocular inflammation

Am J Ophthalmol

Epidemiology of uveitis. Incidence and prevalence in a small urban community

Arch Ophthalmol

New biologic-response modifiers in ocular inflammatory disease: beyond anti-TNF treatment

Expert Rev Clin Pharmacol

Systemic therapies for inflammatory eye disease: past, present and future

BMC Ophthalmol

Nonsteroidal anti-inflammatory therapy and recurrent acute anterior uveitis

Ocul Immunol Inflamm

Ocular immune responses. II. Priming of A/J mice in the vitreous induces either enhancement of or suppression of subsequent hapten-specific DTH responses

J Immunol

Major review
The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management