Outcome of Treating Pediatric Uveitis With Dexamethasone Implants




Purpose


To describe the outcome in children of eyes with uveitis following repeated treatment with dexamethasone (Ozurdex) implants.


Design


Retrospective, interventional study.


Methods


Twenty-two eyes of 16 pediatric patients with uveitis were treated with 35 dexamethasone implants at a tertiary referral center. Following implantations, anatomic and functional outcomes, as well as ocular complications, were noted. Main outcome measures included best-corrected visual acuity, central retinal thickness, number and dosage of systemic immunosuppression drugs, vitreous haze score, and presence of raised intraocular pressure or cataract.


Results


Following the first implantation, average best-corrected visual acuity improved significantly from 0.55 ± 0.08 logMAR to 0.37 ± 0.08 logMAR ( P = .024), central retinal thickness decreased by 219 ± 55 μm ( P = .01), and the percentage of eyes achieving a vitreous haze score of 0 increased from 41% to 88% ( P = .006). The median time to relapse following the first injection was 9 months, with a similar response achieved after each repeat implantation. Children previously requiring systemic immunosuppression at the time of the first implantation were able to stop or significantly reduce the dose and number of drugs. In total there were 4 instances of cataract progression that were not visually significant and did not require surgical treatment and 6 cases of raised IOP, 5 of which were treated pharmacologically with no surgical intervention required and 1 that required revision of a previous filtration surgery. There were no cases of implant migration into the anterior chamber, endophthalmitis, or retinal detachment.


Conclusions


The use of dexamethasone implants in children results in improved retinal thickness and reduction in ocular inflammation, which can improve vision for several months. Repeat implantations result in continued control of the inflammation, allowing for reduction of systemic immunosuppression with few ocular complications.


Uveitis accounts for 10%–15% of the causes of blindness in the developed world. Though pediatric uveitis is relatively uncommon, accounting for only 5%–10% of all uveitis cases, vision-threatening complications are common, with a high rate of vision loss. Ocular inflammation is treated aggressively in order to prevent the occurrence of ocular changes, such as cystoid macular edema (CME), vitreous inflammation, cataract, and retinal scarring, that may lead to vision loss. Treatment is generally based on the use of systemic or regional corticosteroids, which are highly effective in controlling the inflammation, with the addition of second-line immunosuppression drugs in order to supplement the corticosteroids or as corticosteroid-sparing agents. In children the treatment of uveitis is challenging mainly owing to the systemic side effects of these drugs, specifically corticosteroids, which can result in growth retardation, Cushingoid effects, behavioral changes, and related psychosocial problems. Use of regional injections of periorbital corticosteroids and intravitreal triamcinolone acetonide reduces the need for systemic treatment and the risks of systemic side effects, while maximizing the ocular impact. They are widely used in adults and to a lesser extent in children, mainly owing to their short effect and the need for repeat treatment under general anesthesia.


Intravitreal dexamethasone implants (Ozurdex; Allergan, Inc, Irvine, California, USA) have been shown to be effective in treating uveitis in both adults and children, with effects lasting up to 6 months following a single implantation. This allows for less frequent implantations, which further reduces the risk of procedure-related adverse events, as well as a good safety profile, with few patients having cataract progression or increased intraocular pressure, compared to other regional corticosteroid injections. While the effect of a single implant has been reported, the effect of repeat treatment using dexamethasone implants on disease control, visual function, and the use of systemic medications has not yet been explored.


In this study we examined the outcome of repeat intravitreal dexamethasone implants for the treatment of uveitis in children. We examined the cumulative effect of using repeat dexamethasone implantations on clinical outcome, systemic treatment, and complication rates.


Methods


Patient Selection


This is a retrospective study of patients seen at Moorfields Eye Hospital, London, UK (ethical approval for data collection LIGS10201, visual loss in uveitis, Moorfields Eye Hospital research and development ethics review board). The study adhered to the tenets of the Declaration of Helsinki. The study included all pediatric noninfectious uveitis patients seen between the years 2008–2014 who were given an intravitreal dexamethasone implant. Patients were offered treatment with a dexamethasone implant if they had previously responded to a local corticosteroid injection but needed short-term repeated treatments, or when systemic treatment was not well tolerated or was ineffective at low doses. All implantations were performed under general anesthesia, as per national regulations, and were uneventful. Repeat implantations were performed in cases when patients were intolerant to systemic immunosuppression or systemic side effects, such as growth retardation, delayed puberty, and weight gain, clinically outweighed the anesthetic risks. All patients were managed under the care of a single consultant (S.L.). Treatment decisions were determined based on vision, clinical evaluation of active inflammation or presence of CME, response to systemic treatment, and side effects. Following implantation, systemic treatment was reduced with an aim to stop all systemic drugs. The decision to repeat treatment with a dexamethasone implant was based on return of CME on optical coherence tomography (OCT; Spectralis, Heidelberg Engineering, Heidelberg, Germany); a further decrease in visual acuity related to recurrent vitritis, as noted on biomicroscopy; or more than a doubling of the angle of best-corrected visual acuity (BCVA).


Data Collection


Information for each patient was collected according to the length of follow-up, on the day of implantation; at months 1, 2, 3, 6, 12, 18, and 24; and at the patient’s last follow-up visit. From each visit information was recorded including BCVA, central retinal thickness (CRT), intraocular pressure (IOP), and vitreous haze score (range 0–4). BCVA results were converted to logarithm of the minimal angle of resolution (logMAR) for statistical analysis and are presented as logMAR and Snellen equivalent. Furthermore, numbers of topical drugs used for treating inflammation or elevated IOP, as well as systemic and regional corticosteroids and immunosuppressive drugs, were recorded. Postimplantation complications, if occurred, were noted, including development of cataract, raised IOP above 21 mm Hg, migration of implants into the anterior chamber, endophthalmitis, and retinal detachment. Record was made of any treatments that were required to address such complications.


Statistical Analysis


Change in mean BCVA and CRT was compared to the time of each injection using the generalized estimating equation, adjusting for correlation between 2 treated eyes of the same patient and using the Bonferroni correction for multiple tests. Change of BCVA following repeat implantations was calculated using the Spearman correlation. The Pearson χ 2 test was used to analyze the proportion of patients achieving a vitreous score of 0. The Kaplan-Meier estimator was used to examine survival from relapse. SPSS (version 22; SPSS Inc, Chicago, Illinois, USA) was used for all analyses. The accepted level of significance for all tests was α ≤ 0.05. Continuous data are presented as means ± standard error of the mean (SEM).




Results


Twenty-two eyes of 16 patients (9 male, 7 female) were included in this study ( Table ). Eyes were diagnosed as having either intermediate uveitis (n = 14) or posterior/panuveitis (n = 8). Etiologies included Vogt-Koyanagi-Harada syndrome (n = 2), juvenile idiopathic arthritis (n = 2), pars planitis (n = 3), and idiopathic (n = 15). Average age at the time of the first implantation was 13 ± 0.7 years (range 9.5–17 years). At the time of the first implantation (baseline) 9 patients were being treated with systemic prednisolone at an average dose of 26 ± 4 mg. Eleven patients had previously received steroid-sparing agents (8 mycophenolate mofetil, 3 infliximab, 2 azathioprine, 2 methotrexate, 1 cyclosporin), of which 4 were still being treated at baseline (3 mycophenolate mofetil, 1 infliximab). Four eyes received previous orbital floor injections of depomedrone (40 mg/1 mL), 8 had previous intravitreal injections of triamcinolone acetonide (IVTA; 4 mg/0.1 mL). Reasons for treatment with dexamethasone implants included CME in 17 eyes (77.3%) and vitritis in 5 eyes (22.3%) with accompanying papillitis in 1 case. Average follow-up time was 16.1 ± 2.1 months after the first implant (range 2–31.5 months, 28.2 eye years) and 8 eyes had more than 18 months of follow-up. Thirteen eyes (59.1%) received a single implant while 9 (40.9%) had multiple implantations ( Table ). Second implantation occurred an average of 9.4 ± 1.5 months after the first implantation and the third implantation 10 ± 1.1 months after the second.



Table

Baseline Characteristics for Eyes With Pediatric Uveitis Before Beginning Treatment With Dexamethasone Implants



































































Baseline Eye Characteristics N (%)
Eyes 22
Duration of uveitis, mo, mean (SEM) 44.25 (6.26)
Diagnosis
Intermediate uveitis 14 (63.6)
Posterior + panuveitis 8 (36.4)
Reason for treatment
CME 17 (77.3)
Vitritis 5 (22.7)
Baseline visual acuity, logMAR, mean (SEM) 0.55 (0.08)
Severity of vitreous haze at baseline
Score of 0 9 (40.9)
Score of +0.5 to +3 13 (59.1)
Baseline central retinal thickness, μm, mean (SEM) 438.07 (41.85)
Baseline intraocular pressure, mm Hg, mean (SEM) 12.55 (1.01)
Phakic, clear lens at baseline 11 (50)
Steroid responders at baseline 10 (45.5)
Repeat implants
2 implants 6 (27.3)
3 implants 2 (9.1)
4 implants 1 (4.5)

CME = cystoid macular edema; LogMAR= logarithm of the minimal angle of resolution; SEM = standard error of mean.

Most eyes required ozurdex implantations to treat CME.


Response to Treatment


Following the first dexamethasone pellet implantation, average BCVA improved significantly from 0.55 ± 0.08 logMAR (20/71) to 0.37 ± 0.08 logMAR (20/47) at 1 month ( P = .0024, n = 22, Figure 1 , Top), then returned to baseline values by 6 months (0.57 ± 0.1 logMAR, 20/74, n = 16). Repeat OCT scans were performed in 18 eyes and revealed that CRT decreased significantly after the implantation by an average of 219 ± 55 μm at 2 months ( P = .01, Figure 2 , Top), though the effect began declining after 2 months and returned to baseline values by 6 months (−45 ± 61 μm).




Figure 1


Change from baseline in best-corrected visual acuity (BCVA) in eyes with pediatric uveitis following dexamethasone implantations. (Top) Average BCVA for all eyes following the first implantation (n = 22). BCVA significantly improved within 1 month, returning toward baseline by 6 months. (Bottom) A similar pattern was observed following the second implantation (n = 9). LogMAR = logarithm of the minimal angle of resolution. Negative logMAR values indicate improvement. * P value< .05.



Figure 2


Change from baseline in central retinal thickness (CRT) in eyes with pediatric uveitis following dexamethasone implantations. Following the first (Top; n = 22) and second (Bottom; n = 9) implantations, the average CRT improved within 1 month, returning to baseline values by 6 months. * P value < .05.


The percentage of eyes achieving a vitreous haze score of 0 improved from 41% at baseline to 88% at months 1 and 2 ( P = .006 for both), remaining stable until month 6, when the effect was lost (64%, P = .3). Average IOP values remained within normal limits throughout follow-up, from 12.6 ± 1.01 mm Hg at baseline to 17.7 ± 2.5 mm Hg at 2 months and 13.1 ± 1.5 mm Hg by 12 months. Six patients had bilateral dexamethasone pellet implantations with the second eye implanted 210 ± 94 days after the first.


In 9 eyes, repeat dexamethasone implants were inserted ( Table ) and clinical response was similar to that following the first implantation in both BCVA ( Figure 1 , Bottom) and CRT ( Figure 2 , Bottom). After the second implantation BCVA improved from 0.87 ± 0.09 logMAR (20/148) to 0.68 ± 0.12 logMAR (20/95) at 1 month ( Figure 1 , Bottom, P = .003) and CRT decreased by 432 ± 253.8 μm at 1 month ( Figure 2 , Bottom, P = .006). Both remained significantly improved until 6 months, when they returned to baseline values. Although not significant, the percentage of eyes achieving a vitreous haze score of 0 improved from 50% at baseline to 100% at 1 month and declined to 67% by 12 months. Similar trends were seen in eyes receiving a third implant, although no statistical analysis could be performed owing to the small cohort and varied follow-up. A single eye proceeded to have a fourth implantation that also resulted in improved BCVA within 1 month.


Duration of Effect


To examine the duration of effect of dexamethasone implants in noninfectious uveitic eyes, we recorded their time to relapse. This was determined as the first follow-up with foveal thickening and/or doubling of the angle of BCVA together with a vitreous haze score of >0, compared to the best result following treatment. Foveal thickening was determined as CRT greater than the average best CRT + 1 standard deviation (calculated at 2 months post the first implantation as 335.71 μm). Following the first injection the median time to relapse was 9 months (range 2–30 months, Figure 3 , Top), with an overall relapse rate of 61%, and for the second implantation it was 6 months (range 4–7 months, Figure 3 , Bottom), with an overall relapse rate of 71%. There was no significant difference between the times to relapse following either implantation ( P = .18).


Jan 6, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Outcome of Treating Pediatric Uveitis With Dexamethasone Implants

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