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Lječnici kometiraju o uveitisu

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Uveitis describes inflammation that exists in the uveal tract, but the disease course has such a variety of manifestations, iterations and presentations that no simple one-size-fits-all depiction may be appropriate.
Because the uvea covers anatomy in the anterior, intermediate and posterior segments, uveitis can affect each part of the eye, independently or simultaneously. Likewise, different inciting factors, both local and systemic, have been linked to the formation of uveitis, but approximately 50% of cases are considered idiopathic.

Uveitis can mimic other diseases at presentation. In cases of posterior uveitis, the appearance of cells in the vitreous, and cases that are nonresponsive to steroids, can point to lymphoma, which can be treated effectively if diagnosed early. Patients with sclerouveitis should be investigated for potentially lethal systemic autoimmune diseases, including polyarteritis nodosa or Wegener’s granulomatosis.

Regardless of the presentation, experts largely agree that steroid therapy should be the first option for treating most patients with noninfectious uveitis because it can suppress the hallmark inflammation. At a certain point, however, steroids will have to be ceased, and continued inflammation suppression is achieved by steroid-sparing therapy.

C. Stephen Foster, “Steroids are really the only thing that can snuff out the fire quickly, and so if one is talking noninfectious, nonmalignant uveitis, steroids should always be the first step in the care of the patient,” C. Stephen Foster, MD, said. “The eye drives the decision making. The fact that you can’t find something to blame is a secondary matter.”

A ‘stepladder’ approach
The location of the inflammation may dictate where the steroid needs to be delivered and how the steroid is delivered, but the disease’s focal point and exact etiology may not be as important as the clinical needs of the patient. Uveitis remains the third leading cause of blindness in the United States, a statistic that indicates a need for swift and thorough therapy to eradicate inflammation before it can damage the eye beyond repair.

To address that inflammation, Dr. Foster advocates a “stepladder” approach to therapy that begins aggressively to address the immediate danger and proceeds as needed for a particular case. In anterior nonmalignant uveitis, for instance, steroid drops are the most appropriate first-line approach.

The steroid dose should be tapered down and eventually eliminated from use, Dr. Foster said, under the premise that steroid therapy should not extend beyond 6 months. However, rapid elimination of steroid therapy is “often a recipe for real trouble, namely rebound inflammation,” Dr. Foster said.

“Yes, you want them off steroid. Yes, you don’t want them on steroid 6 months after the story began. But one wants to taper relatively slowly,” he said.

Relapsing uveitis may be an indication to add daily oral NSAIDs. However, while that approach is effective in most cases — Dr. Foster said it produces a positive response in 75% to 80% of anterior nongranulomatous recurrent uveitis cases in which the additional therapy is required — it is a regimen that requires patience.

“It’s an approach that too few doctors have tried with some dedication and trying it in sufficient number of cases to get a clear impression to see how it goes,” Dr. Foster said.

The next step may be surgery or chemotherapy.

“The surgery could be something as simple as pars plana vitrectomy with endolasering for somebody with pars planitis or as complex as the installment of a time-release drug delivery device, such as Retisert (fluocinolone intravitreal implant, Bausch & Lomb),” Dr. Foster said. “The chemotherapy may be something as simple as once-a-week methotrexate or as complex as episodic intravenous cyclophosphamide or once-monthly Remicade (infliximab, Centocor).”

Therapy options
Some practice guidelines suggest that immunosuppressive therapy may be appropriate as the first therapeutic option in some cases of uveitis, including sympathetic ophthalmia, Vogt-Koyanagi-Harada disease and Behçet’s disease with retinal vasculitis, and in some rheumatologic disorders, such as Wegener’s granulomatosis, Behçet’s disease or polyarteritis nodosa, which affects the posterior segment.

However, immunosuppressive therapy requires close and careful follow-up, and there are systemic concerns that general ophthalmologists may not be aware of. For that reason, referral to a uveitis specialist may be warranted.

Referral may also be called for if the disease course is particularly violent, if it affects the retina, or if uveitis recurs every time the steroid is tapered down or eliminated. Dr. Foster suggested referral after 6 months of steroid use and said the timing of the referral can be of critical importance.

“Delayed referral is too common, and a change in practice patterns is going to be necessary if we are going to have any significant hope of reducing the prevalence of blindness secondary to uveitis,” Dr. Foster said. “Too often, the uveitis specialist gets the referral, gets the case, after sufficient damage has been done that precludes the patient ever seeing well again.”

Another concern in uveitis is how aggressively the disease course should be treated with respect to eliminating inflammation. According to Dr. Foster, achieving a definitive cure is possible in most cases, and that should be the primary goal of therapy. While on steroid therapy, however, chasing every last cell in the anterior chamber may actually be detrimental.

“I am trying to balance what is good enough and what might be excessive therapy that runs a risk of producing treatment-induced trouble,” Dr. Foster said.

Some patients with uveitis may be at greater risk for developing complications or suffering vision loss, but identifying risk factors that indicate who those patients are remains elusive. One potential area of interest to researchers in anterior uveitis is the level of flare, which is a marker of protein leakage from the vasculature.


Gary N. Holland
In some cases, cells can be completely eliminated, but flare may never return to normal. Nevertheless, according to research conducted by Gary N. Holland, MD, lower levels of flare are *** with lower complication rates and less vision loss, even in the case of persistent anterior cells, which may remain low grade, despite treatment, in some patients.
However, that does not necessarily mean that therapy should be stopped or changed in patients with low flare counts and persistent anterior chamber cells. “The treatment in that group of patients for whom we haven’t been able to eliminate all cells is probably providing some benefit that is not reflected in the reduction of cells,” Dr. Holland said. “Flare is an additional sign of inflammation that we can measure in those patients.”

Even low-grade inflammation can cause damage to the eye that can lead to vision loss. To that end, Dr. Holland said, therapy should aggressively target cell reduction in anterior uveitis or other markers of inflammation, such as macular edema, in other types of uveitis.

“We tend to see patients develop complications early, but the risk probably never goes to zero once the eye has been inflamed,” he said. “I think all uveitis specialists agree that there should be an attempt to suppress all inflammation maximally in adults or children with uveitis. Anterior chamber cells are the easiest sign to monitor for activity of uveitis and to monitor for response to treatment, but are not the only signs that should be considered.”

Because they are fast-acting compared with immunosuppressive agents, steroids may be the most appropriate agents in the initial treatment of inflammation. But given the long-term systemic complications and risks of pressure elevation and cataract *** with steroids, Dr. Holland said that tapering should begin when an endpoint germane to the type of uveitis is achieved, but not later than 1 month after treatment is started, with close monitoring during the subsequent taper for signs of recurrence.

Pediatric uveitis

Cessation of steroid therapy in pediatric patients may be a more delicate and precarious scenario, in large part because uveitis in pediatric patients confers a risk for development of cataracts and glaucoma, and possibly vision loss secondary to the inflammatory response.

Janet L. Davis
In anterior uveitis, particularly with iridocyclitis secondary to juvenile idiopathic arthritis, steroid eye drops are warranted as first-line therapy to help avoid damage from uveitic complications, according to Janet L. Davis, MD, MA. Other forms of uveitis in pediatric patients, such as some idiopathic uveitis, intermediate uveitis or pars planitis, can be observed in lieu of using steroids.

Twenty years ago, treatment guidelines suggested targeting a 2+ cell count in the anterior chamber in juvenile idiopathic arthritis-associated iridocyclitis — the uveitic manifestation with the most thorough treatment paradigms established — but therapeutic options available for pediatric uveitis are more successful in achieving absolute quiescence of inflammation, Dr. Davis said. In turn, that absence of inflammation is necessary to stave off potential damage to the eye that may lead to vision loss.

However, a long duration of topical steroids may not be prudent given the *** risks of developing cataract or glaucoma, and steroids may not be feasible for the patient because instillation may be required hourly, which could interfere with school activities.

“If the topical steroids are not low-dose, well-tolerated, free of complications and achieving excellent control with no cellular inflammation, then methotrexate is usually the next drug that is tried,” Dr. Davis said.

Periocular and oral steroids for treatment of pediatric patients have largely been abandoned due to the potential for adverse outcomes, she said. Additionally, whereas juvenile idiopathic arthritis may lead to poor bone development, use of oral steroids may lead to growth retardation that could further exacerbate the underlying condition.

In particular, cataract formation in pediatric patients, and specifically in patients with uveitis and uveitis secondary to juvenile idiopathic arthritis, is complicated to treat. Inflammation is an immune response, and because immune responses in pediatric patients are generally more profound than in adults, membrane development over an IOL may be triggered. That membrane may create opacity worse than the original cataract or cause traction on the ciliary body and retina that can lead to a hypotonus state, according to Dr. Davis.

Complications related to the opacity of the IOL may require explantation, which confers risk for an enlarged or distorted pupil, as well as long-term loss of accommodation. In patients with juvenile idiopathic arthritis, Dr. Davis noted, “it is not clear how many children can be safely implanted with an IOL.”

“If they acquire a visually significant cataract, they may have to have lensectomy and pars plana vitrectomy, which renders them aphakic, and there is no surety that they will be able to undergo a replacement IOL for the rest of their life. They become dependent on contact lens wear,” she said.

Epidemiology of pediatric uveitis
Uveitis occurs less frequently in children than in adults, but when it occurs in pediatric patients, it may cause a significant disease burden. That may be because a disproportionate number of cases occur secondary to juvenile idiopathic arthritis. Ocular manifestations can precede or follow symptoms *** with juvenile idiopathic arthritis.

However, Dr. Davis said, patient factors *** with juvenile idiopathic arthritis — such as young age at the onset of the arthritis, a positive result on an antinuclear antibody test and pauciarticular arthritis longer than 6 months — may increase the risk of ocular manifestations.

“It’s also true that there can be no joint manifestations that are ever symptomatic or ever detectable on physical examination or that children who are followed for a while for iridocyclitis, which has clinical features of [juvenile rheumatoid arthritis], but never had any joint manifestations, can sometimes develop the joint manifestations after they have developed the uveitis,” Dr. Davis said. “What it means is that the systemic disease has started, but it has become symptomatic in the eyes before the joints for whatever reason.”

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Anita Moorjani "Ponovno rodjena"


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