Oren Tomkins-Netzer

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.

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.

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.

Ischemic retinal vasculitis and its management.

Ischemic retinal vasculitis is an inflammation of retinal blood vessels associated with vascular occlusion and subsequent retinal hypoperfusion. It can cause visual loss secondary to macular ischemia, macular edema, and neovascularization leading to vitreous hemorrhage, fibrovascular proliferation, and tractional retinal detachment. Ischemic retinal vasculitis can be idiopathic or secondary to systemic disease such as in Behçets disease, sarcoidosis, tuberculosis, multiple sclerosis, and systemic lupus erythematosus. Corticosteroids with or without immunosuppressive medication are the mainstay treatment in retinal vasculitis together with laser photocoagulation of retinal ischemic areas. Intravitreal injections of bevacizumab are used to treat neovascularization secondary to systemic lupus erythematosus but should be timed with retinal laser photocoagulation to prevent further progression of retinal ischemia. Antitumor necrosis factor agents have shown promising results in controlling refractory retinal vasculitis excluding multiple sclerosis. Interferon has been useful to control inflammation and induce neovascular regression in retinal vasculitis secondary to Behçets disease and multiple sclerosis. The long term effect of these management strategies in preventing the progression of retinal ischemia and preserving vision is not well understood and needs to be further studied.

Examining the Choroid in Ocular Inflammation: A Focus on Enhanced Depth Imaging

The choroid is the vascular layer that supplies the outer retina and is involved in the pathogenesis of several ocular conditions including choroidal tumors, age related macular degeneration, central serous chorioretinopathy, diabetic retinopathy, and uveitis. Nevertheless, difficulties in the visualization of the choroid have limited our understanding of its exact role in ocular pathology. Enhanced depth imaging optical coherent topography (EDI-OCT) is a novel, noninvasive technique that is used to evaluate choroidal thickness and morphology in these diseases. The technique provides detailed objective in vivo visualization of the choroid and can be used to characterize posterior segment inflammatory disorders, monitor disease activity, and evaluate efficacy of treatment. In this review we summarize the current application of this technique in ocular inflammatory disorders and highlight its utility as an additional tool in monitoring choroidal involvement in ocular inflammation.

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.

Treatment Strategies in Primary Vitreoretinal Lymphoma: A 17-Center European Collaborative Study

IMPORTANCE The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. OBJECTIVE To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. INTERVENTIONS The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. MAIN OUTCOMES AND MEASURES Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. RESULTS Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. CONCLUSIONS AND RELEVANCE In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment.

A Meta-Analysis of Studies Evaluating Visual and Anatomical Outcomes in Patients with Treatment Resistant Neovascular Age-Related Macular Degeneration following Switching to Treatment with Aflibercept

With the introduction of aflibercept, eyes with neovascular age-related macular degeneration (AMD) not responding well to injections of ranibizumab or bevacizumab can be switched to treatment with aflibercept. We carried out a meta-analysis to analyze all available evidence of visual and anatomical outcomes of eyes with resistant neovascular AMD switched to aflibercept at six months. Data from seven retrospective and prospective studies looking at change in best corrected visual acuity (BCVA) and central retinal thickness (CRT) were included. Weighted mean difference (WMD) and 95% CI were estimated using the standardized mean change method. The overall results of the meta-analysis showed a small but statistically significant improvement in BCVA six months following treatment switch to aflibercept (WMD 0.142, 95% CI 0.006 to 0.28; p = 0.04), and the effect was more significant in data gathered from prospective studies (WMD 0.407, 95% CI 0.023 to 0.791, p = 0.038). There was a significant improvement in CRT following treatment switch to aflibercept (WMD −0.36, 95% CI −0.485 to −0.235; p < 0.0001). Our meta-analysis indicates that following treatment switch to aflibercept patients may have a significant improvement in CRT with stabilization or even some improvement in their visual acuity.

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.

Functional outcome of macular edema in different retinal disorders

Macular edema accompanies many ocular pathologies, affecting visual function and is an important factor in treatment decisions and disease outcome. Though visual acuity is commonly used to evaluate patient vision it does not always provide a complete estimate of their visual abilities or reflect their own visual perception. Furthermore, different pathologies result in macular edema causing a variable effect on visual function, related to the rate of fluid accumulation and accompanying ocular changes. Use of complementary visual function tests, such as retinal contrast sensitivity on microperimetry and reading speed provide additional information that can be used to evaluate patients and assist in treatment choices. Here we explore the effect of macular edema on visual function in different retinal pathologies, namely diabetic retinopathy, retinal vein occlusion and uveitis, examine its influence on the various vision tests and discuss the factors underlying this variable response.