The Use of Sustained Release Intravitreal Steroid Implants in Non-Infectious Uveitis Affecting the Posterior Segment of the Eye.

The treatment of non-infectious uveitis affecting the posterior segment of the eye has been revolutionized by the development of sustained-release corticosteroid implants over the past decade. Their use is now supported by healthcare systems that have licensed and commissioned them on the basis of the high-quality randomised controlled trials that formed part of their development and which have informed clinicians as to their benefits and risks. In particular, they have provided an alternative mode of treatment for patients who do not wish to be systemically immunosuppressed, or in whom such immunosuppression is less desirable, such as those with unilateral disease or those with concurrent illnesses such as diabetes mellitus, renal disease or osteoporosis that are negatively impacted by systemic corticosteroids or other immunosuppressive agents. In this article, we review the evidence for the use of the major licensed corticosteroid implants and assess the advantages and disadvantages of each.

Outcomes Associated With Sustained-Release Intraocular Fluocinolone Implants in a Case of Melanoma-Associated Retinopathy Treated Without Systemic Immunosuppression.

Importance: Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome in which antiretinal antibodies crossreact with retinal ON-bipolar cells, resulting in night blindness and progressive visual field loss. Current therapeutic options include cytoreductive surgery in combination with immunoglobulin, corticosteroids, or plasmapheresis, but their effectiveness is limited and may be contraindicated, given the possible protective role of circulating autoantibodies against metastatic spread. We report 3-year follow-up of the first case (to our knowledge) of MAR treated with intravitreal long-acting steroid implants. Objective: To report on a patient with MAR who was treated with intravitreal fluocinolone acetonide implants in the absence of systemic immunosuppression. Design, Setting, and Participants: This is a 3-year follow-up of a 73-year-old woman with a history of surgical excision of a malignant melanoma of the left pinna who presented with visual symptoms of shimmering and nyctalopia. Fundus examination, fundus autofluorescence, and optical coherence tomography were normal, with no evidence of cystoid macular edema. Automated perimetry showed a reduction in visual field and full-field electroretinography (ERG) demonstrated findings consistent with generalized ON-bipolar cell dysfunction, typical of MAR. The patient was treated with bilateral fluocinolone acetonide intravitreal implants. Main Outcomes and Measures: Visual acuity, visual field, and electroretinography testing for 3 years after treatment. Results: Visual fields improved in this 73-year-old patient from 20/30 (Snellen measured as 6/9) OD and 20/16 (6/5) OS at baseline to 20/20 OU within 1 week of treatment. Detailed electroretinography monitoring indicated characteristic abnormalities that partly resolved after treatment, consistent with improved inner retinal ON-bipolar cell function. Bilateral cataracts developed approximately 2 years after injection; cataract surgery was performed uneventfully. At 3 years posttreatment, the patient remained visually stable and in systemic disease remission, with best-corrected visual acuity remaining at 20/20 OU. Conclusions and Relevance: We report what is, to our knowledge, the first case of MAR treated with intravitreal slow-release corticosteroid implants, which shows improvements in visual symptoms, visual fields, and retinal function. Sustained-release intraocular steroid implants may offer an effective and safe alternative to systemic immunosuppression in MAR, although results from 1 case should be generalized with abundant caution.

Sutureless 25-Gauge Pars Plana Vitrectomy Combined with Retropupillary Fixation of an Iris-Claw Intraocular Lens.

BACKGROUND: The surgical case of a dropped intraocular lens inside the vitreous cavity constitutes a real challenge for the operating surgeon. Herein, we describe a case series where an alternative optical rehabilitation technique for late intraocular lens-bag complex dislocation has been used. METHODS: A modern vitrectomy device was used to remove the capsule with the dropped intraocular lens using sutureless 25-gauge pars plana vitrectomy. To ensure a better aesthetic result, with faster patient recovery and a reduced number of operations, the whole procedure was performed during the same operating session; an iris-claw intraocular lens for aphakia was selected for implantation. The implant was passed behind the constricted iris with the concave surface facing it. The lens was grasped with the manufacturer's holding forceps and fixed onto the posterior surface of the iris using the special enclavation needles. RESULTS: We have operated 12 eyes in two different clinical centres successfully, with minimal intra- and/or postoperative complications. CONCLUSION: We believe that this is a viable solution for the visual rehabilitation of patients, who would otherwise need more than one operation for a lens exchange.

Raised Intraocular Pressure in Nonjuvenile Idiopathic Arthritis-Uveitis Children: Risk Factors and Effect on Retinal Nerve Fiber Layer.

PURPOSE: To determine risk factors for intraocular pressure (IOP) elevation and glaucoma in children with nonjuvenile idiopathic arthritis-related uveitis and any IOP-related changes in the retinal nerve fiber layer (RNFL) thickness. PATIENTS AND METHODS: Clinical data were collected from children attending a tertiary referral uveitis clinic between May 2010 and October 2012. We assigned 206 eyes of 103 children into 32 normal eyes, 108 normotensive uveitics (NU), 41 hypertensive uveitics (HU: raised IOP without glaucomatous disc), and 25 glaucomatous uveitics (GU: raised IOP with glaucomatous disc). Risk factors for raised IOP, glaucoma and steroid response (SR) were evaluated and RNFL thickness across groups was compared with determine changes related to raised IOP. RESULTS: IOP elevation occurred in 40 patients (38.8%) or 66/174 eyes with uveitis (37.9%); and SR occurred in 35.1% of all corticosteroid-treated eyes. Chronic uveitis was a significant risk factor for raised IOP [odds ratio (OR)=9.28, P=0.001], glaucoma, and SR (OR=8.4, P<0.001). Higher peak IOP was also a risk factor for glaucoma (OR=1.4, P=0.003). About 70% of SR eyes were high responders (IOP increase >15 mm Hg from baseline), associated with younger age and corticosteroid injections. Although no significant RNFL thinning was detected between HU and NU eyes, significant thinning was detected in the inferior quadrant of GU (121.3±28.9 µm) compared with NU eyes (142.1±32.0 µm, P=0.043). CONCLUSIONS: Children with chronic uveitis are at higher risk of raised IOP and glaucoma. Thinning of the inferior RNFL quadrant may suggest glaucomatous changes in uveitic children with raised IOP.

Long-term Outcomes of Rituximab Therapy in Ocular Granulomatosis with Polyangiitis: Impact on Localized and Nonlocalized Disease.

PURPOSE: To evaluate the long-term outcomes of rituximab (RTX) treatment in patients with ocular granulomatosis with polyangiitis (GPA) with localized or generalized disease. DESIGN: Retrospective cohort. PARTICIPANTS: Thirty-seven patients with ocular GPA receiving RTX in a multidisciplinary vasculitis clinic between 2004 and 2013. METHODS: A total of 100 patients who received a course of RTX were identified, and notes were reviewed. Baseline demographic details, clinical characteristics (including organ involvement), drugs used, and outcome measures were recorded. MAIN OUTCOME MEASURES: The percentage in remission (inactive disease with prednisolone ≤7.5 mg with or without maintenance treatment) at 6 months, time to remission, percentage relapsing, side effects, B-cell count, antineutrophil cytoplasm antibody titers, induction, and maintenance regimens. RESULTS: The median follow-up time after the first RTX course was 36.5 months. Twenty patients had scleritis, and 17 patients had orbital disease; 86% achieved remission at 6 months. The percentage in remission versus partial remission was not statistically significant between patients with scleritis and patients with orbital disease (85% vs. 15% with scleritis and 82% vs. 18% with orbital disease; P = 1.00). The percentage relapsing was not statistically significant (P = 0.33) between scleritis (60%) and orbital disease (41%). Localized disease (ocular ± ear-nose-throat/lung) was observed in 57%, and generalized disease (ocular plus other organs) was observed in 43%, the former having a median duration of disease of 40 months. There was no statistically significant difference (P = 0.37) in the percentage in remission between localized and generalized ocular disease. Relapses occurred in 51%, with localized disease being a significant risk factor for relapse. Fifty percent of patients with generalized disease versus none with localized disease received cyclophosphamide (CYP) as part of the induction regimen. Patients who received CYP during induction had significantly (P = 0.027) lower ratios of baseline 12-month proteinase 3 titers than patients who did not have CYP. Infections were observed in 16% of patients, with 8% requiring hospital admission. CONCLUSIONS: Our long-term data suggest that RTX is effective for inducing disease remission in localized and generalized ocular GPA. Localized disease is a significant risk factor for relapse, which may be related to less use of CYP in the induction regimen.

Treatment of diabetic maculopathy.

Diabetic maculopathy is an important cause of severe sight impairment. There has been a significant evolution in its treatment over the past decade and laser treatment is now largely being superseded by intravitreal injections of anti-vascular endothelial growth factor agents or corticosteroids.

Long-term clinical outcome and causes of vision loss in patients with uveitis.

PURPOSE: To evaluate the long-term clinical and functional outcome, risks, and causes of vision loss and burden of disease among patients with uveitis. DESIGN: Cross-sectional study. PARTICIPANTS: The study included 1076 patients diagnosed with uveitis who attended the uveitis clinic at Moorfields Eye Hospital, London, United Kingdom, between 2011 and 2013. METHODS: Information was gathered from the notes of all patients who were examined in the clinic. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), causes of moderate vision loss (MVL; 20/50-20/120), and severe vision loss (SVL; ≤ 20/200). RESULTS: The study included 1799 eyes of 1076 patients with an average follow-up of 7.97 ± 0.17 years (median, 5.6 years; range, 1 month-54 years; 8159 patient-years; 14 226 eye-years). Average BCVA remained stable for patients with anterior uveitis (20/30 at baseline to 20/33 at 10 years), as well as for those with nonanterior uveitis (20/50 at baseline to 20/47 at 10 years). Vision loss was noted in 19.2% of eyes, with an incidence for MVL of 0.01 per eye-year or 0.02 per patient-year and for SVL of 0.01 per eye-year or 0.02 per patient-year. Patients were more at risk of vision loss if they had non-anterior uveitis disease, vitreous opacities, retinal detachment, cystoid macular edema (CME), macular scarring, macular hole, optic neuropathy, or macular ischemia. Chronic CME was the most common cause of MVL (3.55%), and macular scarring was the most common cause for irreversible SVL (4%). Among 525 patients (48.7%) who received oral prednisolone, 320 (61%) required a dose of more than 40 mg/day and 130 (24.8%) also required 1 or more second-line agents. Patients were reviewed on average 33.7 ± 0.7 times or 5.9 ± 0.46 times/year. CONCLUSIONS: Long-term functional outcome among uveitis patients is good, with BCVA remaining stable for more than 10 years of follow-up. In cases when vision loss occurs, it is related mainly to retinal changes. The burden on clinical services is similar regardless of the severity of disease or the risk of vision loss.

Birdshot chorioretinopathy.

PURPOSE OF REVIEW: Birdshot chorioretinopathy remains incompletely understood, but new insights into its pathogenesis have been reported recently, and treatment and monitoring options have also expanded. Central visual acuity may remain good until the late stages of the disease, but loss of visual field and peripheral retinal function is common. RECENT FINDINGS: The underlying pathogenesis of the disease has long been believed to be T-cell driven, but examination of the IL-17 pathway has now further refined the potential underlying mechanism. New imaging techniques, including extended depth imaging of the choroid with optical coherence tomography, have demonstrated promise in detecting disease activity earlier, enabling targeted treatment to be given. Treatment options have expanded with the advent of the biological agents, and these may yet improve outcomes, particularly in refractory patients. SUMMARY: Laboratory research continues to investigate the underlying mechanisms of disease, but our understanding remains frustratingly incomplete for a disease with such a clear HLA association. Clinical research is increasingly being driven to improve the phenotyping of affected patients so that those at risk of visual loss can be identified early and treated more aggressively with individually targeted therapies such as the newer biological agents, but how successful this approach will ultimately prove to be remains to be seen.

Evaluation of retinal nerve fiber layer thickness in eyes with hypertensive uveitis.

IMPORTANCE: Uveitic glaucoma is among the most common causes of irreversible visual loss in uveitis. However, glaucoma detection can be obscured by inflammatory changes. OBJECTIVE: To determine whether retinal nerve fiber layer (RNFL) measurement can be used to detect glaucoma in uveitic eyes with elevated intraocular pressure (IOP). DESIGN, SETTING, AND PARTICIPANTS: Comparative case series of RNFL measurement using optical coherence tomography performed from May 1, 2010, through October 31, 2012, at a tertiary referral center. We assigned 536 eyes with uveitis (309 patients) in the following groups: normal contralateral eyes with unilateral uveitis (n = 72), normotensive uveitis (Uv-N) (n = 143), raised IOP and normal optic disc and/or visual field (Uv-H) (n = 233), and raised IOP and glaucomatous disc and/or visual field (Uv-G) (n = 88). EXPOSURES: Eyes with uveitis and elevated IOP (>21 mm Hg) on at least 2 occasions. MAIN OUTCOMES AND MEASURES: Comparison of RNFL values between groups of eyes and correlation with clinical data; risk factors for raised IOP, glaucoma, and RNFL thinning. RESULTS: Mean (SD) global RNFL was thicker in Uv-N (106.4 [21.4] µm) compared with control (96.0 [9.0] µm; P < .001) eyes and was thicker in Uv-N eyes with active (119.6 [23.2] µm) compared with quiescent (102.3 [20.8] µm; P = .001) uveitis, which in turn was not significantly different from control eyes (P = .07). Compared with Uv-N eyes, significant RNFL thinning was seen in all quadrants except the temporal in Uv-G eyes and significant thinning in the inferior quadrant of Uv-H eyes with no evidence of disc or visual field changes (P = .03). Risk factors for elevated IOP were male sex and anterior uveitis. Age, higher peak IOP, longer duration of follow-up, and uveitis-induced elevation of IOP were risk factors for glaucoma and RNFL defect. CONCLUSIONS AND RELEVANCE: Screening for glaucomatous RNFL changes in uveitis must be performed during quiescent periods. Thinning of the inferior quadrant suggests that glaucomatous damage, more than uveitic ocular hypertension, is in fact occurring. Measurement of RNFL may detect signs of damage before disc or visual field changes and therefore identifies a subgroup that should receive more aggressive treatment.

Treatment with repeat dexamethasone implants results in long-term disease control in eyes with noninfectious uveitis.

PURPOSE: To describe the long-term outcome of eyes with uveitis after repeated treatment with dexamethasone implants (Ozurdex; Allergan, Inc., Irvine, CA). DESIGN: Retrospective, observational case series. PARTICIPANTS: Thirty-eight eyes of 27 patients with uveitis that were treated with 61 dexamethasone implants. METHODS: All eyes underwent dexamethasone pellet implantation. Anatomic and functional outcomes, as well as ocular complications, were noted. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), central retinal thickness (CRT), vitreous haze score, and presence of increased intraocular pressure or cataract. RESULTS: Average follow-up was 17.3 ± 1.8 months after the first implant (median, 13.3 months; range, 3-54.5 months; 54.65 eye-years), with 14 eyes (36.9%) receiving a single implant and 24 eyes (63.1%) receiving multiple implantations. After the first implantation, average BCVA improved significantly from 0.47 ± 0.05 logarithm of the minimum angle of resolution (logMAR) units (Snellen equivalent, 20/60) to 0.27 ± 0.07 logMAR (Snellen equivalent, 20/37; P<0.001); CRT decreased by 263 ± 44.22 µm (P = 0.003), although macular edema persisted in 50% of eyes, and the percentage of eyes achieving a vitreous haze score of 0 increased from 58% to 83% (P = 0.03). The median duration of therapeutic effect after the first injection was 6 months (range, 2-42 months), with a similar response achieved after each repeat implantation. The accumulated effect of repeat dexamethasone implants resulted in a continued improvement in BCVA (R(2) = 0.91; P<0.0001), with significant improvement and stabilization of CRT. After repeated implantations, 2 eyes had progression of posterior subcapsular opacities, although neither required surgery. There were 7 instances of increased intraocular pressure of more than 21 mmHg at a rate of 0.13 per eye-year, all of which responded to pharmacologic treatment. CONCLUSIONS: The accumulated effect of repeat dexamethasone pellet implantations improves retinal thickness and resolves ocular inflammation, resulting in restoration of ocular function. Ocular complications were minimal, with no eyes requiring surgery for increased ocular pressure or progression of cataract.

Outcomes of changing immunosuppressive therapy after treatment failure in patients with noninfectious uveitis.

PURPOSE: To evaluate the outcomes of changing immunosuppressive therapy for noninfectious uveitis after failure. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with noninfectious uveitis managed at 2 tertiary uveitis clinics in the United Kingdom and Australia. METHODS: Participants with a history of using immunosuppressive therapy were identified in clinics, and notes were reviewed by doctors trained in uveitis therapy. Each treatment episode/course (starting or changing a therapy) was identified, and demographic details, clinical characteristics, drug used (second-line immunosuppressive agent [ISA] or biologicals), and drug doses were obtained. MAIN OUTCOME MEASURES: For each treatment episode, the reasons for changing therapy, corticosteroid-sparing effects, and control of inflammation were determined. RESULTS: A total of 147 patients were identified who underwent 309 different treatment episodes. Fifty-five percent of patients eventually required a change in treatment after their first treatment episode/course. Forty-five episodes involved switching from one ISA to another, with 50% to 100% of these patients achieving "success" (prednisolone ≤10 mg and sustained control) with the new ISA. A combination of ISAs were used in 53 episodes, with "success" being achieved in 50% to 71% of these patients. Biological agents were used in 45 episodes, the most common one being infliximab, which achieved success in 80% of patients. CONCLUSIONS: Our data suggest that control of inflammation can be achieved after switching or combining ISAs.

Long-term clinical and anatomic outcome of birdshot chorioretinopathy.

IMPORTANCE: Birdshot chorioretinopathy is a chronic intraocular inflammatory disease with no uniform method to document long-term disease progression or response to treatment. OBJECTIVE: To examine the long-term visual, clinical, and anatomic outcomes of patients with birdshot chorioretinopathy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective evaluation of 46 patients with birdshot chorioretinopathy treated at Moorfields Eye Hospital, London, England, was conducted. Medical records for a 19-year period (1993-2012) were reviewed. EXPOSURES: Patients received no treatment, short-term (≤1 year) treatment including local or systemic corticosteroids, or long-term (>1 year) treatment including systemic corticosteroids and second-line immunosuppressive agents. MAIN OUTCOMES AND MEASURES: Details regarding clinical and anatomic outcome, including best-corrected visual acuity, and visual field indices were evaluated. RESULTS: Ninety-two eyes of 46 patients were monitored for a mean (SE) of 57.2 (5.8) months (445 eye-years, 17% follow-up of ≥10 years). Patients maintained a steady best-corrected visual acuity throughout the follow-up period. Some clinical indices correlated with transient worse best-corrected visual acuity, including presence of cataract (P = .05), foveal leakage on fluorescein angiography (P = .04), and increased central retinal thickness (P = .02). Serial visual field studies demonstrated that patients who received only short-term treatment had a worsening of their pattern standard deviation with time (Spearman correlation, 0.57; P = .003); for those who received long-term treatment, the pattern standard deviation remained stable (Spearman correlation, -0.24; P = .26). CONCLUSIONS AND RELEVANCE: Our results suggest that central visual acuity can be maintained long term in patients with birdshot chorioretinopathy. Those who receive long-term immunosuppression appear to maintain better peripheral visual fields compared with patients who receive short-term treatment.

Successful corticosteroid-sparing effect of rituximab in the treatment of refractory idiopathic orbital inflammatory disease.

Idiopathic orbital inflammatory disease (IOID) is an idiopathic inflammatory process within the orbit that can result in permanent visual impairment. Although high-dose oral corticosteroids are currently the mainstay of therapy, their long-term usage can cause significant toxicity. We present a case of IOID that was successfully treated with the anti-CD20 monoclonal antibody rituximab following failed steroid sparing with conventional second-line immunosuppressive agents.

Can rituximab induce long-term disease remission in patients with intra-ocular non-infectious inflammation?

Treatment of non-infectious uveitis is based primarily on the use of systemic corticosteroids and second-line immunosuppressive drugs. However, their extensive side effect profile, particularly for steroids, has led to the increased use of other immunosuppressive drugs, as sparing capacity agents. Rituximab is an anti-CD20 chimeric antibody, often given as a single course of 2 infusions, resulting in complete depletion of peripheral mature B cells. While it is licensed to treat refractory systemic lymphoma patients, it has also shown promising results in systemic auto-immune diseases, where a single course of treatment is able to achieve long-term clinical remission. Treatment with rituximab has been reported for various ocular conditions, suggesting it may be effective in inducing long-term disease control and other systemic immunosuppressive agents can be reduced or discontinued. When disease relapse occurs, a further course or courses can be given with good results. This review summarizes the current evidence regarding the role of rituximab in treating non-infectious uveitis.

Local therapies for inflammatory eye disease in translation: past, present and future.

Despite their side-effects and the advent of systemic immunosuppressives and biologics, the use of corticosteroids remains in the management of patients with uveitis, particularly when inflammation is associated with systemic disease or when bilateral ocular disease is present. The use of topical corticosteroids as local therapy for anterior uveitis is well-established, but periocular injections of corticosteroid can also be used to control mild or moderate intraocular inflammation. More recently, intraocular corticosteroids such as triamcinolone and steroid-loaded vitreal inserts and implants have been found to be effective, including in refractory cases. Additional benefits are noted when ocular inflammation is unilateral or asymmetric, when local therapy may preclude the need to increase the systemic medication.Implants in particular have gained prominence with evidence of efficacy including both dexamethasone and fluocinolone loaded devices. However, an appealing avenue of research lies in the development of non-corticosteroid drugs in order to avoid the side-effects that limit the appeal of injected corticosteroids. Several existing drugs are being assessed, including anti-VEGF compounds such as ranibizumab and bevacizumab, anti-tumour necrosis factor alpha antibodies such as infliximab, as well as older cytotoxic medications such as methotrexate and cyclosporine, with varying degrees of success. Intravitreal sirolimus is currently undergoing phase 3 trials in uveitis and other inflammatory pathways have also been proposed as suitable therapeutic targets. Furthermore, the advent of biotechnology is seeing advances in generation of new therapeutic molecules such as high affinity binding peptides or modified high affinity or bivalent single chain Fab fragments, offering higher specificity and possibility of topical delivery.

Dexamethasone implants in retinal vein occlusion: 12-month clinical effectiveness using repeat injections as-needed.

OBJECTIVE: To report the 12-month outcomes of the dexamethasone intravitreal implant in retinal vein occlusion (RVO), using an as-needed repeat injection protocol. DESIGN: Retrospective consecutive case series of 51 eyes of 49 patients with macular oedema as a result of RVO that received an intravitreal dexamethasone implant and were followed up for at least 12 months. RESULTS: 70% of patients responded to dexamethasone implant injection with an improvement in visual acuity (VA) and macular oedema within 3 months of injection, but only 30% of eyes gained ≥15 letters. The mean change in VA letter score at 12 months compared with baseline for branch RVO (BRVO) and central RVO (CRVO) was 5.7±2.3 and 11.5±11.0 EDTRS letters, respectively. 56% of patients relapsed, with the median time to relapse being 17 weeks for patients with branch RVO and 18 weeks for patients with CRVO. Repeat injections achieved similar VA gains, but the duration of effect of repeat dexamethasone implants was much shorter at 10 weeks. 14 eyes (27%) developed a significant rise in intraocular pressure, and three of these required treatment with oral acetazolamide. Four eyes with CRVO developed neovascular glaucoma during the study. CONCLUSIONS: The intravitreal dexamethasone implant does not last the 6 months implied by the retreatment protocol in the GENEVA trial, and improved results can be achieved with an as-needed retreatment protocol, particularly in CRVO. However, visual outcomes remain similar to those previously seen with triamcinolone in the SCORE study and neovascular complications remain a feature of CRVO.

Intraocular methotrexate can induce extended remission in some patients in noninfectious uveitis.

PURPOSE: To assess the outcomes of the intravitreal administration of methotrexate in uveitis. METHODS: Multicenter, retrospective interventional case series of patients with noninfectious uveitis. Thirty-eight eyes of 30 patients were enrolled, including a total of 54 intravitreal injections of methotrexate at a dose of 400 µg in 0.1 mL. The primary outcome measure was visual acuity. Secondary outcome measures included control of intraocular inflammation and cystoid macular edema, time to relapse, development of adverse events, and levels of systemic corticosteroid and immunosuppressive therapy. RESULTS: Methotrexate proved effective in controlling intraocular inflammation and improving vision in 30 of 38 eyes (79%). The side effect profile was good, with no reported serious ocular adverse events and only one patient having an intraocular pressure of >21 mmHg. Of the 30 eyes that responded to treatment, 8 relapsed, but 22 (73%) entered an extended period of remission, with the Kaplan-Meier estimate of median time to relapse for the whole group being 17 months. The eight eyes that relapsed were reinjected and all responded to treatment. One eye relapsed at 3 months, but 7 eyes again entered extended remission. Of the 14 patients on systemic therapy at the start of the study, 8 (57%) were able to significantly reduce this following intravitreal methotrexate injection. CONCLUSION: In patients with uveitis and uveitic cystoid macular edema, intravitreal MTX can effectively improve visual acuity and reduce cystoid macular edema and, in some patients, allows the reduction of immunosuppressive therapy. Some patients relapse at 3 to 4 months, but a large proportion (73%) enter an extended period of remission of up to 18 months. This larger study extends the results obtained from previous smaller studies suggesting the viability of intravitreal methotrexate as a treatment option in uveitis.