In Light of Treating Noninfectious Posterior Segment Uveitis

In Light of Treating Noninfectious Posterior Segment Uveitis

August 31, 2022

The terms intermediate uveitis, posterior uveitis, and panuveitis are only a few of the diagnostic terms used to describe uveitis of the posterior region. Although the majority of instances with posterior segment uveitis are noninfectious, certain cases can be contagious.

The foundations for treating noninfectious uveitis in the posterior region include corticosteroids and immunomodulatory medications. The utilization of intraocular injections/implants or systemic medications is typically required for the treatment of posterior uveitis.

Uveitis is the third most common cause of vision loss in developed nations and a significant contributor to vision loss worldwide.

Uveitis is divided into anterior (iritis, iridocyclitis, and anterior cyclitis), intermediate (pars planitis, posterior cyclitis, and hyalitis), and posterior categories based on the location of the inflammation (focal, multifocal, or diffuse choroiditis, chorioretinitis, retinitis, and neuroretinitis).

The vitreous, retina, choroid, and anterior chamber are all inflamed in panuveitis. The most frequent type of uveitis is anterior, and posterior uveitis accounts for 15% to 22% of all occurrences.

The most challenging type of uveitis to treat is posterior uveitis, which can cause visual morbidity and presents difficulties in administering treatment medications at levels that are effective.

Chronic noninfectious posterior segment uveitis refers to inflammation of the retina, choroid, vitreous, or optic nerve, and may result in permanent vision loss.

The inflammation may be ongoing or manifest as recurrent flare-ups of a preexisting baseline of inflammation.

The ophthalmologist must make a number of choices when a patient exhibits ocular inflammation, the characteristic of uveitis.

Identifying whether the illness is infectious or noninfectious is the first and most important difficulty because it will decide the appropriate treatment course.

Practitioners have a choice between local and systemic therapy for patients who have noninfectious posterior uveitis. If local therapy is chosen, there are new medical choices accessible for both topical and intravitreal treatments.

It may be prudent for the ophthalmologist to consult the patient's internist or, in some circumstances, a rheumatologist during either diagnosis or treatment due to the complexity of the ailment and particular patient.

Although effective uveitis management is challenging, today's therapy choices are safer, more effective, and more streamlined than in the past and hold out the hope of long-lasting symptom remissions.

If neglected, a category of inflammatory illnesses known as uveitis can cause serious visual loss. According to estimates, there are between 17 and 52 cases of uveitis per 100,000 people per year, with a prevalence of 38 to 714 instances per 100,000 people.

Uveitis can develop as a result of systemic inflammatory disorders or as a localized eye condition; between 24% and 55% of cases are thought to be idiopathic. Uveitis can cause inflammation of the lens, retina, optic nerve, and vitreous in addition to the uvea.

Uveitis can also affect the posterior segment, anterior segment, or both. It can also be infectious or noninfectious, acute or chronic. Depending on the type and location of inflammation, different symptoms, such as blurred vision, floaters, eye pain, redness, and light sensitivity, may be present.

Uveitis must be treated promptly and effectively since, if left untreated, its repeated inflammation can affect patients' functioning and quality of life and even cause vision loss.

Uveitis frequently offers a diagnostic and therapeutic difficulty because it can have a variety of origins and affect different types and amounts of tissue.

Similar ocular and neurological symptoms are frequently found in inflammatory, infectious, and malignant eye disorders.

As a result, diagnosing and treating complex, persistent, or refractory patients sometimes calls medical expertise in internal medicine, infectious diseases, rheumatology, and immunology.

Retinal experts who are knowledgeable with therapies and procedures for the posterior segment are typically the ones who treat posterior uveitis.

Practitioners caring for patients with uveitis confront a number of obstacles, including making an accurate diagnosis, treating the acute phase of the disease, and preventing symptom recurrence. This is due to the complexity of uveitis diagnosis and therapy.

Therefore, it is crucial to instruct healthcare professionals on the diagnosis and management of uveitis. We will describe significant technological developments in posterior segment drug administration and offer advice for navigating the noninfectious posterior uveitis pathway.

Diagnostic Challenges

Diagnosis is the first step in treating patients with uveitis. Practitioners undertake a series of steps and tests to determine if a patient has uveitis and, if so, which type.

Classifying Uveitis

Uveitis is characterized in two ways, anatomic and etiologic. The ophthalmologist is responsible for anatomic categorization, although collaboration with other medical professionals may be necessary for etiologic classification.

Ophthalmologists perform clinical tests to categorize suspected instances of uveitis based on which tissues exhibit inflammation.

Anterior uveitis, sometimes called iritis, is the medical term for inflammation that develops at the front of the eye. Panuveitis is the diagnosis when inflammation spreads over the entire eye as opposed to just the back of the eye.

The inspecting physician must make sure that any apparent anterior uveitis does not have a posterior component and vice versa in order to rule out panuveitis. The retina and choroid are frequently affected when uveitis develops in the posterior portion of the eye.

After anterior and panuveitis, respectively, posterior uveitis is the third most prevalent kind of uveitis in the US. However, posterior uveitis, which accounts for 53% of nonanterior instances in people under the age of 65, is more common than other types of nonanterior inflammation. Optical News

According to the Standardization of Uveitis Nomenclature (SUN) classification, posterior uveitis includes focal, multifocal or di­ use choroiditis, chorioretinitis, retinochoroiditis, retinitis, and neuroretinitis.

When compared to anterior uveitis, posterior uveitis has a worse prognosis and higher morbidity. Macular edema, cataract, glaucoma, vitreous debris, and retinopathy are problems associated with noninfectious posterior uveitis that can be life-threatening to patients' vision.

Macular edema is the most common structural complication of uveitis that causes central visual impairment, followed by epiretinal membrane and glaucoma (6.3% and 4.2%, respectively). Macular edema was reported in 8.3% of patients with noninfectious uveitis in a retrospective analysis of 334 patients from the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS).

Etiologic classification: Uveitis can result from infectious or noninfectious causes, and the appropriate treatment depends on the reason. Etiological diagnosis is difficult since infectious and noninfectious uveitis can have many comparable clinical symptoms and indications.

The practitioner can only shift their attention from treating infectious rather than inflammatory processes once an infectious etiology has been ruled out.

Clinical Examination: The clinical examination is one of the most important steps in correctly diagnosing and treating uveitis.

A red, painful eye accompanied by anterior chamber cell and flare, posterior synechiae, and keratic precipitates are the clinical signs of anterior uveitis. In addition to chorioretinal lesions, retinal bleaching, and vascular sheathing, posterior uveitis worsens vision and alters the visual field.

An anterior chamber specimen may need to be used in a PCR assay if vitreous inflammation prevents visibility of the posterior region.

Along with choroidal inflammation, inflammation in the posterior segment may also affect nearby structures like the retina, vitreous, optic nerve head, or retinal arteries.

Therefore, it may be useful for the examining physician to keep the following inquiries in mind as the investigation progresses: Is this inflammation choroiditis, retinitis, or retinochoroiditis?

Are the retinal vessels or the head of the optic nerve involved? Do the clinical characteristics point to a recognized infectious or noninfectious entity? Exist any problems, vitritis, or inflammation in the anterior segment? Does the disorder have any further systemic characteristics? Is it ongoing?

If so, how has treatment in the past gone? Lastly, is an immunocompromised state a factor? History: A thorough medical history will help identify any potential infectious conditions the patient may be suffering from.

In addition to any known infectious disorders, such as tuberculosis or Lyme disease, ophthalmologists should inquire about any prior inflammatory episodes or infections in the eye, such as herpes or varicella.

Practitioners should enquire about any high-risk sexual behavior that can increase the patient's chance of contracting syphilis or the human immunodeficiency virus. Furthermore, contact with pets or other animals may indicate toxoplasmosis or toxocaraiasis.

Toxoplasmosis was the most frequent cause of posterior uveitis in a 2015 study by Bajwa et al. Practitioners should inquire about previous hospitalizations or diseases. Significant systemic consequences from syphilis, TB, sarcoidosis, and Lyme disease can all result in uveitis.

Syphilis must be ruled out in patients who are adults and teenagers. The internist of the patient could be able to offer crucial background data that will aid in the diagnosis.

Age range: Depending on the patient's age, underlying disorders that affect uveitis etiologies or severity may manifest more or less frequently.

For instance, juvenile rheumatoid arthritis, Behçet's disease, or ankylosing spondylitis are more prevalent in younger people, whereas it's crucial to rule out cancer or syphilis in elderly patients.

Ophthalmologists can also request a series of laboratory tests to ascertain whether uveitis is brought on by bacteria, viruses, fungi, or another source. A full workup for uveitis would include a complete blood count as well as sedimentation rate.

Rheumatoid factor, antinuclear antibodies to rule out rheumatoid arthritis, and angiotensin-converting enzyme for sarcoidosis are examples of additional blood tests. To rule out ankylosing spondylitis in younger patients with back discomfort, a simple lumbo-sacral X-ray or an HLA-B27 test would be beneficial.

If the patient has cats or dogs or has been exposed to other animals, the practitioner should test for toxoplasmosis or toxocaraiasis. A skin test, blood interferon-gamma release assay, or chest X-ray should be conducted to rule out tuberculosis.

The presence or type of an infection in the eye may also be determined using imaging techniques such fundus fluorescein angiography (FFA), indocyanine green angiography (ICG), ultrasonography (USG), and optical coherence tomography (OCT).

Idiopathic uveitis: As has been noted, up to half of uveitis cases will, after careful workup, be classified as idiopathic.

However, it has been suggested that some “idiopathic” cases may reflect incomplete patient medical history or imperfect laboratory testing and may actually be uveitis secondary to sarcoidosis, tubulointerstitial nephritis, or ankylosing spondylitis.

Treatment Challenges

The first goal of treatment is to suppress the inflammation and improve the patient’s symptoms quickly. The second goal is to prevent recurrences and thereby prevent the damage to optical tissues that can lead to permanent vision loss.   

Treatment: Local or systemic: The presence of unilateral, bilateral, or unilateral alternating uveitis should be taken into account when selecting whether to utilize local or systemic treatment.

Only one eye is affected at a time and the assaults are repeated in unilateral alternating illness, which can affect either eye. In cases of unilateral uveitis, local therapy is more likely to be used.

For noninfectious uveitis, topical steroids are frequently used as the initial treatment. The advantage of topical steroids is that they are generally safe and simple to stop using. Additionally, they don't penetrate very far past the anterior chamber, thus they won't exacerbate an infectious condition.

However, because to their limited penetration, steroids are less effective than alternative treatments, including injections, in the posterior portion.

Due to the effectiveness and safety of the dexamethasone intravitreal implant, patients with noninfectious, locally-treated posterior segment uveitis are likely to begin receiving intravitreal steroids.

Although the dexamethasone intravitreal implant has a brief duration of action, it is effective at large doses. Within two weeks of starting, it reaches its peak, and the advantages endure for around four months.

The dexamethasone intravitreal implant can raise IOP like other steroids, however the elevations do not seem to be cumulative.

The fluocinolone actetonide (FAc) intravitreal implant is frequently beneficial as maintenance therapy in patients with unilateral uveitis who continue to have recurrent flare-ups following initial treatment with an intravitreal steroid.

Many doctors will decide to start noninfectious uveitis patients on the dexamethasone intravitreal implant then switch them over to the FAc intravitreal implant, which is long-acting even at low doses, once the inflammation is under control and any macular edema has disappeared.

Systemic corticosteroids, biologics like adalimumab and infliximab, or immunosuppressive drugs like methotrexate are some choices for systemic treatment.

When topical corticosteroids are insufficient or when a systemic condition that also requires treatment is present in the patient, systemic corticosteroids may be administered for patients with bilateral symptoms.

Although extremely effective, systemic medication for noninfectious uveitis also has a severe side effect profile. Rheumatologists are specialists who have experience managing the adverse effects of these medications, so practitioners prescribing systemic therapy may want to speak with one before starting treatment.

Every patient is unique, thus systemic therapy must be based on the etiology of the patient's disease and customized to the patient's circumstances.

Some patients might not be good candidates for systemic medication due to contraindications, such pregnancy, when the risk of drug teratogenicity must be taken into account; other patients could just prefer local treatment.

Insurance coverage and cost are two other factors that frequently come into play with systemic treatments for uveitis. Questions about localized treatments: Intraocular pressure (IOP) rise and cataract are the two main issues with local treatments.

The frequency of mild ( 23 mmHg) and moderate ( 25 mmHg) ocular hypertension increases with repeated injections, but the frequency of severe ( 30 mmHg) ocular hypertension does not change with injection frequency, according to a study looking at the frequency and degree of ocular hypertension associated with sequential injections of the dexamethasone intravitreal implant.

Therefore, it is unlikely that subsequent implants will result in an IOP spike of greater than 30 mmHg if a patient does not experience one after a single implant. Despite the dexamethasone implant's therapeutic advantages, 27% to 32% of patients have reported experiencing brief IOP spikes.

In a retrospective study of 306 charts of patients who got the dexamethasone implant for a range of illnesses, including posterior uveitis, the significance of these spikes in terms of long-term vision loss was evaluated.

Eligible patients were divided into cross-sectional and prospective groups depending on the following criteria:                            

• Cross sectional: IOP spikes ≥ 22 mm Hg up to 16 weeks post-implant and OCT retinal nerve fiber layer (RNFL) imaging of both eyes performed ≥ 3 months after the IOP spike (N = 48)

• Prospective: OCT RNFL imaging performed within one year prior to dexamethasone implantation, IOP spike ≥ 22 mmHg up to 16 weeks after DEX implant, and OCT RNFL imaging performed ≥ 3 months after the IOP spike (N = 21) Up to 48% of these patients had a prior history of glaucoma.

In the cross-sectional group, IOP spikes ≥ 22 mmHg after dexamethasone implantation demonstrated no significant di­fference in average RNFL thickness when compared with the contralateral untreated eye regardless of treatment diagnosis, magnitude of IOP spike, or history of glaucoma.

Similarly, the prospective group also demonstrated no significant di­ erences in average RNFL thickness when comparing measurements before and at least 3 months after the IOP spike.

This study showed that a temporary elevation of IOP after dexamethasone implantation does not appear to cause a meaningful change in RNFL thickness when treated with IOP-lowering drops, regardless of etiology or magnitude of IOP increase.

Additionally, even in patients with a prior ocular history of glaucoma, topical IOP-lowering drops appeared to be sufficient in this study's management of transient IOP spikes to prevent RNFL damage.

Due to the possibility of cataracts with intravitreal steroids, topical therapy may be preferable in younger patients. Contrarily, inflammation itself has the potential to result in the formation of cataracts, so it is important to engage these patients in a discussion of the advantages and disadvantages.

Patients older than 40 years old, who are typically more prone to be concerned about IOP, may find the idea of cataract surgery to be less intimidating.

It is crucial to prevent uveitis recurrences throughout time, regardless of the patient's age, as repeated episodes can harm ocular structures and induce vision deterioration.

Additionally, the loss of retinal pigment epithelium brought on by the persistent macular edema linked to recurrent uveitis has a negative impact on visual acuity. When treating a patient with noninfectious posterior uveitis, the right therapy must be chosen on an individual basis, much like the diagnosis.

The manner or frequency of delivery, contraindications to systemic or local therapy, the patient's medical and optical history, and other factors, such as patient preferences, may all affect the outcome.

Balancing treatment with job responsibilities is a major concern for many adult uveitis patients. Subtenon injections may be useful in some situations, particularly for patients with cystoid macular edema.

To provide safe, effective, and long-lasting relief from uveitis symptoms while also meeting the patient's demands, the practitioner must take into account all of these criteria.

The Multicenter Uveitis Treatment Trial (MUST):

Over a 7-year period, MUST compared the FAc 0.59 mg insert with systemic therapy (prednisone at first, with the addition of an immunosuppressive drug if necessary).

The best corrected visual acuity (BCVA) difference between the FAc implant and systemic therapy groups at 2 years was negligible.

After 4.5 years, the implant offered improved inflammation control. Nevertheless, after 7 years, 180 patients' visual outcomes were better in the systemic therapy treatment group, despite the fact that those getting systemic therapy had a greater risk of infections that required antibiotic treatment.

At 7 years, 45% of eyes in the FAc implant group had undergone glaucoma surgery compared with 12% of eyes in the systemic therapy group. In phakic eyes, 90% of patients in the implant group had had cataract surgery versus 50% in the systemic therapy group.

Kempen 2017

These findings imply that local control is effective during the early years. It might eventually be required to switch patients to systemic therapy, though, if they have underlying illnesses such systemic rheumatologic disease.

IOP data for 249 patients were available in relation to IOP rises with FAc treatment in MUST. IOP was elevated by at least 10 mmHg above the baseline measurement in at least 65% of patients assigned to the implant and in only 24% of individuals assigned to systemic medication in the first two years of follow-up.

Over the course of the two years, 32% of patients allocated to the implant versus 5% of patients assigned to systemic therapy underwent surgical intervention (P 0.001), and 69% of patients assigned to the implant got IOP-lowering therapy as opposed to 26% in the systemic treatment arm.

IOP increases were frequent in the first year for implant patients: 58% of them had increases of at least 10 mmHg. At least 8 additional patients in the implant group experienced incident IOP increase of 10 mmHg or higher at 12 months.

In patients assigned to implants, the median period from implant surgery to an IOP increase of at least 10 mmHg was 9 months. Once an incident occurred in one eye of patients with bilateral implants, the chance of an IOP increase or of needing IOP-lowering surgery was greater in the other eye.

Nine of the 27 (23%) participants allocated to receive implants also developed glaucoma in both eyes. Regardless of the initial treatment method, all cases of glaucoma that were seen were in eyes that received implants, with the exception of 4 eyes in 4 patients.

IOP reaction to steroids is typically quite predictable. Most IOP responders show up rather soon, around the second or third injection. It is improbable that someone who doesn't respond to steroids early on will do so later.

The MUST investigators advised that all patients receiving the FAc implant should have their IOP checked at least every 6 weeks and possibly more frequently due to the risk of damage if left untreated.

Patients with non-infectious posterior uveitis will probably need many office visits and collaboration with different medical specialists. Practitioners will have to gather and analyze many pieces of information from various sources.

Coordination of this data is necessary to develop a treatment strategy that is both effective and practical. The illness management and prognosis for these patients have significantly improved thanks to newer medicines and better knowledge of how to use them.

Uveitis patients now have more e­ icacious, safer, and less expensive treatment alternatives, which o­ er a larger promise for preserving eyesight, independence, and quality-of-life over the long term.