Uveitic Cystoid Macular Edema Research Articles

Intravitreal VEGF levels in uveitis patients and treatment of uveitic macular oedema with intravitreal bevacizumab

Clinical data suggest a role for VEGF in uveitic cystoid macular oedema (CME), even though the data on intravitreal VEGF levels in these eyes is still inconclusive. We determined intravitreal VEGF levels and treated uveitis patients with intravitreal bevacizumab. Intravitreal VEGF levels were measured in eight uveitis patients and 10 controls using cytometric bead array technology. In 11 eyes of a second group of uveitis patients, CME was treated using 1.25 mg bevacizumab intravitreally. Re-injections of bevacizumab were given in patients showing a transient positive effect, defined as an increase of the best-corrected vision of at least two lines on a snellen chart. Alternatively, triamcinolone was given in patients, not responding to bevacizumab. Mean intravitreal VEGF concentration was 82.75+/-171.71 pg/ml (+/-SD) (range, 0.0-502.1 pg/ml), and below the detection levels in controls. A significant reduction of retinal thickness was seen at weeks 2 (P=0.001) and 4 (P=0.007). A significant improvement in VA was seen at week 2 (P=0.02). Patients presenting with a CME in baseline fluorescein-angiogram responded well towards bevacizumab treatment, unless an extensive leakage from the choroid or a leakage of the optic disk was detectable. In these patients, only intravitreally administered triamcinolone led to a reduction of the CME. Our data suggest that patients presenting with a diffuse leakage from the choroid in the fluorescein angiogram or an extensive leakage of the optic disk should be treated with intravitreal triamcinolone, whereas in patients presenting only a cystoid macular oedema bevacizumab treatment seems like a good choice.

Treatment of cystoid macular edema with the new-generation NSAID nepafenac 0.1%

To describe the use of nepafenac 0.1% for cystoid macular edema (CME). This was a multicenter retrospective review of 22 CME cases (20 patients) treated with nepafenac 0.1% (six with concomitant prednisolone acetate 1%) from December 2005 to April 2008: three acute pseudophakic CME cases, 13 chronic/recalcitrant pseudophakic CME cases, and six cases of uveitic CME. Pre- and post-treatment retinal thickness and visual acuity were reported. Following treatment for six weeks to six months, six eyes with uveitic CME showed a mean retinal thickness improvement of 227 +/- 168.1 mum; mean best-corrected visual acuity (BCVA) improvement was 0.36 +/- 0.20 logMAR. All three cases of acute pseudophakic CME improved after four to 10 weeks of nepafenac, with a mean improvement in retinal thickness of 134 +/- 111.0 mum. BCVA improved in two patients (0.16 and 0.22 logMAR) but not in the third due to underlying retinal pigment epithelium changes. Thirteen eyes with chronic/recalcitrant pseudophakic CME demonstrated a mean improvement in retinal thickness of 178 +/- 128.7 mum after nepafenac and mean BCVA improvement of 0.33 +/- 0.19 logMAR. The positive outcomes of these 22 eyes strongly suggest that nepafenac 0.1% is a promising drug for the treatment of CME. Additional study under randomized controlled conditions is warranted.

Short-term Safety and Efficacy of Intravitreal Triamcinolone Acetonide for Uveitic Macular Edema in Children

To evaluate the short-term safety and efficacy of intravitreal (IV) triamcinolone acetonide (TA) for treating pediatric cystoid macular edema (CME) secondary to noninfectious uveitis. A retrospective noncomparative interventional case series. The medical records of 15 consecutive children (16 eyes) with uveitic CME treated with IVTA (2 or 4 mg) were reviewed. Data collected included details of uveitis, CME, visual acuity, intraocular pressure, and cataract development. The median follow-up time was 16 months (range, 9-36 months). Resolution of CME was achieved in all of the treated eyes. The median time taken for CME to resolve was 3 weeks (range, 1-24 weeks). The mean improvement of visual acuity after IVTA was 0.6 logarithm of the minimum angle of resolution. Following initial response to IVTA, CME relapsed in 5 eyes (31%) after a median time of 7 months (range, 3-13 months). The most common adverse effect was increased intraocular pressure, with an increase of more than 15 mm Hg in 5 eyes (31%). Steroid-induced cataract was observed in 6 of 11 phakic eyes (55%). We found that IVTA is efficacious in the treatment of uveitic CME in children and results in CME resolution and visual acuity improvement. As in adults, treatment in children may be associated with elevated intraocular pressure and cataract.

INTRAVITREAL BEVACIZUMAB (AVASTIN) AS A TREATMENT FOR REFRACTORY MACULAR EDEMA IN PATIENTS WITH UVEITIS

: Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) which has been successfully used for the treatment of age-related macular degeneration with choroidal neovascularization. As VEGF is involved in the pathomechanisms of inflammation and endothelial dysfunction the authors used bevacizumab as a last resort treatment in patients with persistent uveitic cystoid macular edema (CME). : Persistent uveitic CME was defined by optical coherence tomography (OCT) measurements >250 mum despite previous treatments. The authors reviewed patients with persistent CME who subsequently had been treated with intravitreous bevacizumab 1.25 or 2.5 mg. Improvement was judged by visual acuity (VA) gain >/=2 lines and thickness reduction in OCT. : Eleven eyes of 10 patients were injected since February 2006. Median follow-up was 70 days. Reduction in central retinal thickness could be seen as early as 2 weeks with a mean foveal thickness reduction of 127.2 mum at 4 weeks. Concurrent improvement in VA was seen in 4 of 10 patients, and was unchanged in the others. Four patients received two injections and five patients received three injections. Except for progression of cataract in one eye no ocular or systemic adverse events were recorded. : Intravitreal bevacizumab seems to be an effective and safe treatment in the management of refractory inflammatory CME. The effect is transient, and reinjections may be necessary, although the time until reinjection is needed differs individually.

Topical nepafenac 0.1% for treatment of chronic uveitic cystoid macular edema.

To describe the efficacy of nepafenac ophthalmic suspension 0.1% (Nevanac; Alcon Laboratories, Inc.) for treating cystoid macular edema (CME) resulting from uveitis. Interventional case series : Three patients with a history of decreased visual acuity due to uveitic CME despite previous treatment with topical steroids or traditional nonsteroidal antiinflammatory drugs, intravitreal triamcinolone acetonide (Kenalog; Bristol-Myers Squibb), or immunosuppressive agents were given topical nepafenac 0.1%. Patients were monitored for clinical improvement, decreased retinal thickness by optical coherence tomography, and improved Snellen visual acuity. For all three patients, treatment with topical nepafenac for 4 weeks to 3 months led to improvement in visual acuity and decrease in retinal thickness. The improved visual acuity and decreased retinal thickness in these patients suggest that nepafenac is an effective treatment of inflammation and CME in the posterior segment of the eye for patients with chronic uveitis.

TUMOR NECROSIS FACTOR ANTAGONISTS

The anti-tumor necrosis factor (TNF) monoclonal antibody infliximab and the soluble TNF receptor etanercept inhibit the pleiotropic actions of TNF and are widely used for the treatment of rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), spondyloarthropathies (SpA), Crohn's disease, and psoriasis with an acceptable safety profile. A pathogenetic role of TNF in ocular inflammatory conditions has recently emerged from small trials reporting preliminary results on the efficacy of these agents in patients with noninfectious uveitis, regardless of the origin of the disease. The authors review the published experience, derived mostly from investigator-sponsored trials and uncontrolled case series, on the use of TNF antagonists in approximately 280 patients with various ocular conditions who were inadequately controlled on currently available therapy. These reports suggest that TNF antagonists, mainly infliximab, which may have better efficacy than etanercept, are useful in the treatment of ocular inflammation associated with Adamantiades-Behçet's disease, RA, JIA, SpA, Crohn's, sarcoidosis, and Graves' disease ophthalmopathy. Infliximab was also beneficial in small numbers of patients with idiopathic uveitis or scleritis, birdshot retinochoroiditis, uveitic and diabetic cystoid macular edema, and age-related macular degeneration. The currently available data are nonrandomized and thus preliminary, providing the foundation and justification for randomized trials to assess efficacy and safety. Until such results are available, knowledge regarding the use of anti-TNF regimens in ophthalmology is incomplete. However, the preliminary evidence points to a growing optimism for targeting TNF in patients with ocular inflammation.

Intravitreal Bevacizumab for Treatment of Uveitic Macular Edema

To evaluate the short-term safety and efficacy of intravitreal bevacizumab for the treatment of cystoid macular edema (CME) secondary to uveitis. Retrospective, noncomparative, interventional case series. Thirteen patients undergoing treatment for recalcitrant uveitic macular edema at one referral center. Charts of patients who received one 2.5-mg intravitreal injection of bevacizumab in one eye were reviewed for clinical information including best-corrected Snellen visual acuity (VA), examination findings, optical coherence tomography (OCT) results, and fluorescein angiography results. Kaplan-Meier survival analysis was used to calculate probability success rates. The statistical significance of change in mean retinal thickness and VA was assessed using repeated-measures analysis of variance. Assessments of changes in best-corrected Snellen VA and OCT retinal thickness were made. Six (46.15%) patients had a decrease in foveal thickness at the end of the follow-up, whereas 5 (38.4%) patients had an improvement of VA by > or =2 lines 84 days or more after the injection. Mean retinal thickness showed a significant decrease over the follow-up (P<0.02). The change in mean logarithm of the minimum angle of resolution VA over the follow-up was not significant (P>0.05). Survival analysis showed that the probability of any improvement in VA increased progressively starting at 6 weeks and reached 81% at 14 weeks. No significant ocular or systemic adverse effects were observed. These results suggest that a single intravitreal injection of bevacizumab is well tolerated and is associated with short-term improvement in VA and decreased OCT retinal thickness in a considerable proportion of patients with uveitic CME resistant to conventional therapy. Further evaluation of intravitreal bevacizumab for uveitic CME in controlled randomized studies is warranted.

Etanercept monotherapy induces complete resolution of cystoid macular edema in a patient with intermediate uveitis.

There is controversy on whether etanercept, an anti-tissue necrosis factor agent, shares infliximab's purported efficacy in the treatment of intermediate uveitis and, in particular, intermediate uveitis-associated cystoid macular edema. Interventional case report. A 29-year-old patient with decreased vision bilaterally secondary to cystoid macular edema complicating chronic idiopathic intermediate uveitis refractory to oral corticosteroids, methotrexate (17.5 mg weekly), and cyclosporine (100 mg daily) started etanercept monotherapy with rapid and complete resolution of cystoid macular edema and dramatic improvement in visual acuity. Etanercept may have a role in the treatment of refractory intermediate uveitis and intermediate uveitis-associated cystoid macular edema.

Uveitis: Intravitreales Triamcinolon bei zystoidem Makulaödem

Cystoid macular edema (CME) is the most frequent cause of severe loss of visual acuity in uveitis. Among the systemic corticosteroids and immunosuppressive agents, the local use of intravitreal triamcinolone acetate (TA) is evaluated. Intravitreal injections of 10 mg TA were performed in ten eyes of six patients with persisting uveitic CME in spite of systemic cortisone or immunosuppressive therapy. The mean follow-up time was 9.8 months (range: 3-18). Visual acuity increased from 0.58 logMAR to 0.21 logMAR. In two eyes of one patient, repeated intravitreal injections of TA were necessary. Side effects included a increase of intraocular pressure (IOP) up to 25 mmHg or more in 30% of the eyes. In these three eyes, IOP was successfully controlled by local antiglaucomatous therapy (IOP < or = 20 mmHg). The dosage of systemic steroids had to be augmented in two eyes. In no patient was injection-related endophthalmitis, vitreous hemorrhage or retinal detachment observed. Intravitreal TA is an effective local therapy for CME due to uveitis without systemic side effects. It cannot replace the systemic basal therapy of uveitis, since the long-term effects are limited. It can be used as a bridging therapy until a systemic immunosuppression is started. It may, furthermore, be a therapeutic option when side effects of immunosuppressive agents are expected.

Octreotide as a Treatment for Uveitic Cystoid Macular Edema

Octreotide as a Treatment for Uveitic Cystoid Macular Edema

INTERFERON ALFA-2A: A NEW TREATMENT OPTION FOR LONG LASTING REFRACTORY CYSTOID MACULAR EDEMA IN UVEITIS?

To perform a prospective pilot study to evaluate interferon alfa-2a (IFN alfa-2a) for the treatment of refractory cystoid macular edema (CME) in endogenous uveitis. IFN alfa-2a was administered at an initial dose of 3 or 6 million IU (depending on body weight) per day subcutaneously. Afterwards IFN alfa-2a was tapered slowly over 6 months and finally discontinued. If CME relapsed IFN alfa-2a was reinstituted and tapered slowly again to evaluate the lowest maintenance dose to keep remission. A total of 15 eyes of 8 patients with refractory CME due to intermediate or posterior uveitis were included. Ineffective pretreatment consisted of systemic steroids and acetazolamide (all patients) and at least one additional immunosuppressant (6 patients). Six of 8 patients (11 eyes) responded well to IFN alfa-2a and CME resolved completely during 6 months treatment. One patient was lost to follow-up after IFN alfa-2a was stopped. In 1 patient (1 eye) even 19 months after cessation of IFN alfa-2a no recurrence of CME occurred. In 4 patients (8 eyes) IFN alfa-2a had to be reinstituted because CME relapsed. All 4 patients responded again. During a mean follow-up period of 16.4 months since restart of therapy we succeeded in all 4 patients to taper IFN alfa-2a to maintenance doses between 1.5 million IU every second and every sixth day without a recurrence of CME in any of the 8 eyes. IFN alfa-2a can be a treatment option for patients with otherwise treatment resistant uveitic CME.

Intravitreal steroids in the management of macular oedema

The use of intravitreal corticosteroids in the management of macular oedema has recently gained widespread acceptance. New long-acting steroid preparations and methods of delivery have facilitated the use of these new modalities. This review describes the various types of macular oedema for which this therapeutic option is used and the results.

The Pros and Cons of Intravitreal Triamcinolone Injections for Uveitis and Inflammatory Cystoid Macular Edema

Intravitreal triamcinolone acetonide (IVTA) injections are gaining in popularity and are regularly administered nowadays for various ocular diseases. This paper presents a literature review on the use, efficacy, and complications of IVTA application in non-infectious uveitis and inflammatory cystoid macular edema (CME). In addition, we describe the experiences of our own institute. IVTA applications brought about a quick improvement in vision in the majority of cases. Drawbacks included the temporary duration of the effect with the need for repeated injections which re-exposed patients to the risk of complications. The risk of bacterial endophthalmitis was 0.5% and was further influenced by the specific IVTA preparation. Based on the literature review, we chose ready-for-use IVTA injections prepared by our pharmacy department, in which 90% of the toxic additives were removed and the dispensed dose of triamcinolone acetonide was validated to diminish the risk of endophthalmitis. Elevated intraocular pressure (IOP) was seen in 30–43% of the eyes and cataract developed in 29% of the eyes of patients, who were usually of advanced age. In conclusion, the rapid effect of IVTA might be of value in severe presentations of non-infectious uveitis and CME and might shorten the time interval needed for the improvement.

Outcome of Intravitreal Triamcinolone in Uveitis

To report the short-term outcome of intravitreal triamcinolone acetate (TA) in the treatment of uveitic cystoid macular edema (CME). Retrospective noncomparative (nonrandomized, uncontrolled) interventional case series. Sixty-five eyes of 54 patients with uveitis-related CME inadequately responsive to treatment combinations of oral corticosteroid, periocular orbital floor corticosteroid injections, and second-line immunosuppressive agents. Intravitreal injection of 4 mg/0.1 ml of TA. Visual acuity (VA), intraocular pressure (IOP), levels of inflammation, and immunosuppressive therapy were assessed. Other potential complications, including cataract progression, vitreous hemorrhage, endophthalmitis, and retinal detachment (RD), were looked for. The mean follow-up was 8.0 months (range, 3-51), and the mean improvement of VA after intravitreal TA was 0.26 (from 0.65 to 0.39 logarithm of the minimum angle of resolution; Snellen, 6/24-6/12, approximately). This occurred at a mean of 4 weeks (range, 1-30). The improvement in VA was more significant if the duration of CME before intravitreal TA was < or =12 months (P = 0.006) and if patients were < or =60 years old (P = 0.005). Patients with the worst vision before treatment also improved the least. The most important side effect was raised IOP (mean rise, 10.3 mmHg), with 28 eyes (43.1%) experiencing an IOP rise of >10 mmHg. Patients younger than 40 years were more likely to experience this IOP rise than those older than 40. Thirty-three eyes (51%) were treated with antiglaucoma medications, with a mean duration of treatment of 17.4+/-13.3 weeks, and no patient required trabeculectomy or lost vision. The dosage of oral corticosteroids and/or second-line immunosuppressive medication was reduced or stopped altogether in 18 of 33 eyes (54.5%) during the study period. There were no cases of injection-related vitreous hemorrhage, endophthalmitis, or RD. In patients with uveitic CME, intravitreal TA can effectively reduce CME and improve VA and, in some eyes, allows the cessation and/or reduction of immunosuppressive therapy. The period of effectivity varies in different patients and, in some eyes, is limited. Treatment was associated in 43.1% with a rise in IOP, which was transient and treatable medically.

Intravitreal triamcinalone acetonide for refractory uveitic cystoid macular oedema: longterm management and outcome

To establish the role of intravitreal triamcinalone acetonide (TA) in the long term management of refractory uveitic cystoid macular oedema (CMO) and to determine the long term visual outcome in these patients. This is a retrospective observational case series. All patients had resistant CMO and active inflammation. The primary outcome measure was complete resolution of CMO on ocular coherence tomography. Visual acuity and intraocular pressure were also monitored. Twelve eyes of twelve patients received 2 (n = 10) to 4 (n = 2) mg of intravitreal TA. All had previously been unresponsive to orbital floor steroids. Fluorescein angiography was performed where indicated. There was complete resolution of CMO in all patients. Nine patients had improvement in acuity at there final follow up (mean follow up 40.5 months). Seven had improved by 2 lines (58%). In 3 patients there was no visual improvement. These 3 failed to respond to re-treatment. Five other patients were re-treated because of recurring CMO and deteriorating VA (median time to re-treatment 4 mths). The mean number of re-treatments for this group with orbital floor TA was three. 41.6% of patients developed ocular hypertension (33.8 mhg mean). One required a trabeculectomy. 2 mg of intravitreal TA is effective even in cases of resistant uveitic CMO. Although re-treatment is often required, the initial response to treatment can be maintained by subsequent orbital floor steroid injections.

LONG-TERM EFFECT OF ACETAZOLAMIDE TREATMENT OF PATIENTS WITH UVEITIC CHRONIC CYSTOID MACULAR EDEMA IS LIMITED BY PERSISTING INFLAMMATION

To assess the long-term effect of acetazolamide treatment on patients with cystoid macular edema (CME) in the course of intermediate or posterior chronic uveitis and to define those patients who may particularly benefit from the drug. Fifty-two eyes (45 patients) with chronic uveitic CME were treated with acetazolamide at an initial dosage of 500 mg/d. The effect of treatment was assessed by fluorescein angiography, ophthalmoscopy, visual acuity, and Amsler testing. Therapy was withdrawn when CME did not improve at 3 weeks. In cases with CME improvement, the dosage was gradually tapered. The mean follow-up was 3.1 years (minimum, 1.5 years). Two subgroups were identified: group 1, quiescence of uveitis with acetazolamide as the single therapeutic agent (33 eyes); and group 2, chronically active uveitis requiring additional systemic antiinflammatory drugs (19 eyes). In both groups, visual acuity improvement was statistically significant (group 1, P = 0.012; group 2, P = 0.025). In 12 patients with a stable visual acuity gain, the medication dose could be tapered off completely without any recurrent edema shown by fluorescein angiography after a minimum follow-up of 1 year. Sixteen patients required a maintenance dosage, ranging from 125 to 500 mg daily. No major adverse effects of the medication were observed. During long-term follow-up, low-dose acetazolamide can be a useful therapeutic option for chronic CME in uveitis. The effect was better in patients with quiescence of uveitis than in those with chronically active uveitis. Permanent therapy is not imperative in every case.

Somatostatin for Uveitic Cystoid Macular Edema (CME)

Purpose: To report the favorable response of bilateral recalcitrant uveitic cystoid macular edema (CME) to treatment with a somatostatin analog. Methods: Medical ophthalmic history and the results of ophthalmic examinations were recorded. Fluorescein angiography (FA) studies were reviewed. Results: A 52-year-old white female with intermediate uveitis developed bilateral recalcitrant CME. Treatment with subcutaneous injections of the somatostatin analog octreotide resulted in partial resolution of the CME and improvement of visual acuity. Conclusions: Somatostatin may play a role in the treatment of CME secondary to uveitis.

Pars plana vitrectomy in cystoid macular edema of different forms of chronic uveitis

Cystoid macular edema (CME) is a common complication in different forms of chronic uveitis. In spite of immunosuppressive and anti-inflammatory therapy, chronic or relapsing courses can occur which may have a negative impact on visual prognosis. Pars plana vitrectomy (PPV) is known to positively influence chronic uveitis. This retrospective study was performed to investigate the role of PPV in the therapy refractive uveitic CME. PPV for CME was performed in eyes with CME in intermediate uveitis (IMU, n=42), chronic iridocyclitis in juvenile rheumatoid arthritis (CIC, n=14) and multifocal chorioretinitis (MFC, n=12). In none of the eyes had immunosuppressive and/or anti-inflammatory therapy or anti-edema treatment (e.g.acetazolamide) led to regression of the CME. After a postoperative follow-up period of 7 and 106 months all patients were re-examined. Postoperative complete or partial regression of CME was observed as follows: IMU: 25/42 (59.5%), CIC: 8/14 (57.1%),MFC: 5/12 (41.7%). A significant increase in visual acuity of 2 lines and more was observed in 50%,71.4% and 41.7% of eyes, respectively. In the long-term follow-up best functional results were achieved in eyes with IMU. Response to PPV was variable according to the type of underlying form of uveitis. The lowest success rate could be observed in eyes with MFC. Although the postoperative regression rate of CME was satisfactory in eyes with CIC, long-term visual acuity results were disappointing due to secondary complications of CIC in this young age group. Best results were achieved in patients with IMU (statistically not significant). A multicenter study in a larger series of patients is needed to investigate the exact role of PPV in different forms of chronic uveitis.

Medical treatment of cystoid macular edema

Although cystoid macular edema (CME) represents a major cause of visual loss in uveitis, the consensus on its treatment has not yet been reached. We performed a literature review on the efficacy of diverse medical treatment modalities for uveitic CME and suggest novel treatment recommendations. A literature search retrieved 173 citations (MEDLINE, conducted in March 2002, terms: macular edema, uveitis, treatment) and relevant publications were studied. The literature contained information based mainly on case series; the specific treatment targets were not clear. Causal treatment of the underlying ocular condition was considered essential and various approaches of symptomatic treatment were attempted (immunosuppressive and immunomodulatory agents, acetazolamide, octreotide), all with different inclusion criteria and evaluation protocols. The decision to initiate the symptomatic treatment of CME was usually made in cases with already compromised visual acuity. Despite aggressive treatment, the progression of CME with accompanying visual loss was common. On the basis of published results, we recommend starting treatment of CME at an early stage, even in eyes with full visual acuity. Randomized clinical trials are needed to determine the efficacy of diverse treatment modalities and to evaluate the effects of early intervention on inflammatory CME.

Recent Developments in the Treatment of Posterior Uveitis

Uveitis is an intraocular inflammation that can be caused by infection, autoimmune disease, trauma or malignancy. It is a serious cause of visual handicap and therapy is targeted at: removal of possible infectious agents, the immunological processes that lead to or sustain the inflammation and finally to prevent or treat the destructive effects of the inflammation on the delicate ocular structures. In this review the latest developments concerning the treatment of posterior uveitis are illuminated, e. g., new approaches concerning the treatment of infectious uveitis including the therapy of herpes virus (VZV, HSV and CMV), bacterial and toxoplasma infections of the eye. Several new ways to influence the immune response and inflammation are described including the use of interferons, modulation of cytokines, soft steroids, other new immunosuppressive drugs and treatment of autoimmune uveitis by oral tolerization. An overview is given to illustrate new ways to administer drugs into eyes, such as intravitreal devices. Finally new developments in the field of the treatment of the various complications of uveitis (cystoid macular edema) are described.