Comparison of anatomical and functional outcomes of treating myopic choroidal neovascularization with bevacizumab or ranibizumab.

PURPOSE: To compare results of treatment with bevacizumab and ranibizumab injections in myopic choroidal neovascularization (mCNV). METHODS: Retrospective, observational case series. PARTICIPANTS: patients with mCNV treated with bevacizumab or ranibizumab injections. Best corrected visual acuity (BCVA) and central retinal thickness (CRT) on optical coherence tomography (OCT) scans were collected at baseline, after 3, 6, 12, 24 months and the last visit. MAIN OUTCOME MEASURES: mean change in BCVA and CRT. RESULTS: We included 85 eyes treated with bevacizumab and 125 eyes treated with ranibizumab. There was no difference between the groups regarding BCVA and CRT change. CNV recurrence occurred at the mean time of 66.1 ± 3.7 and 57.3 ± 6.4 months in the bevacizumab- and ranibizumab-treated eyes, respectively (p = 0.006). During the first year 6.9% eyes in the bevacizumab group vs. 27.5% in the ranibizumab group had CNV recurrence (p = 0.001). Risk factors for recurrence of CNV were baseline CNV area (aHR 1.20, 95%CI 1.0-1.32, p = 0.04), subfoveal CNV (aHR 2.13, 95% CI 1.16-3.93, p = 0.01) and ranibizumab treatment (aHR 2.31, 95% CI 1.16-3.93, p = 0.008). CONCLUSION: Eyes treated with bevacizumab and ranibizumab can achieve similar anatomical and functional improvement. CNV recurrence may occur earlier and more frequently during the first year in eyes treated with ranibizumab.

Adhesion Molecule Targeted Therapy for Non-Infectious Uveitis.

Non-infectious uveitis (NIU) is an inflammatory eye disease initiated via CD4+ T-cell activation and transmigration, resulting in focal retinal tissue damage and visual acuity disturbance. Cell adhesion molecules (CAMs) are activated during the inflammatory process to facilitate the leukocyte recruitment cascade. Our review focused on CAM-targeted therapies in experimental autoimmune uveitis (EAU) and NIU. We concluded that CAM-based therapies have demonstrated benefits for controlling EAU severity with decreases in immune cell migration, especially via ICAM-1/LFA-1 and VCAM-1/VLA-4 (integrin) pathways. P-selectin and E-selectin are more involved specifically in uveitis related to vasculitis. These therapies have potential clinical applications for the development of a more personalized and specific treatment. Localized therapies are the future direction to avoid serious systemic side effects.

Functionally distinct IFN-γ+ IL-17A+ Th cells in experimental autoimmune uveitis: T-cell heterogeneity, migration, and steroid response.

Immunopathogenic roles for both Th1 (CD4+ IFN-γ+ ) and Th17 (CD4+ IL-17A+ ) cells have been demonstrated in experimental autoimmune uveitis (EAU). However, the role for Th17/Th1 (CD4+ T cells co-expressing IFN-γ and IL-17A) cells in EAU is not yet understood. Using interphotoreceptor retinoid-binding protein peptide-induced EAU in mice, we found increased levels of Th17/Th1 cells in EAU retinae (mean 9.6 ± 4.2%) and draining LNs (mean 8.4 ± 3.9%; p = 0.01) relative to controls. Topical dexamethasone treatment effectively reduced EAU severity and decreased retinal Th1 cells (p = 0.01), but had no impact on retinal Th17/Th1 or Th17 cells compared to saline controls. Using in vitro migration assays with mouse CNS endothelium, we demonstrated that Th17/Th1 cells were significantly increased within the migrated population relative to controls (mean 15.6 ± 9.5% vs. 1.9 ± 1.5%; p = 0.01). Chemokine receptor profiles of Th17/Th1 cells (CXCR3 and CCR6) did not change throughout the transendothelial migration process and were unaffected by dexamethasone treatment. These findings support a role for Th17/Th1 cells in EAU and their resistance to steroid inhibition suggests the importance of targeting both Th17 and Th17/Th1 cells for improving therapy.

Small-molecule antagonist of VLA-4 (GW559090) attenuated neuro-inflammation by targeting Th17 cell trafficking across the blood-retinal barrier in experimental autoimmune uveitis.

BACKGROUND: The integrin VLA-4 (α4ß1) plays an important role in leukocyte trafficking. This study investigated the efficacy of a novel topical α4ß1 integrin inhibitor (GW559090, GW) in a mouse model for non-infectious posterior uveitis (experimental autoimmune uveitis; EAU) and its effect on intraocular leukocyte subsets. METHODS: Mice (female; B10.RIII or C57Bl/6; aged 6-8 weeks) were immunized with specific interphotoreceptor retinoid-binding protein (IRBP) peptides to induce EAU. Topically administered GW (3, 10, and 30 mg/ml) were given twice daily either therapeutically once disease was evident, or prophylactically, and compared with vehicle-treated (Veh) and 0.1% dexamethasone-treated (Dex) controls. Mice were sacrificed at peak disease. The retinal T cell subsets were investigated by immunohistochemistry and immunofluorescence staining. The immune cells within the retina, blood, and draining lymph nodes (dLNs) were phenotyped by flow cytometry. The effect of GW559090 on non-adherent, adherent, and migrated CD4+ T cell subsets across a central nervous system (CNS) endothelium was further assayed in vitro and quantitated by flow cytometry. RESULTS: There was a significant reduction in clinical and histological scores in GW10- and Dex-treated groups as compared to controls either administered therapeutically or prophylactically. There were fewer CD45+ leukocytes infiltrating the retinae and vitreous fluids in the treated GW10 group (P < 0.05). Immunofluorescence staining and flow cytometry data identified decreased levels of retinal Th17 cells (P ≤ 0.001) in the GW10-treated eyes, leaving systemic T cell subsets unaffected. In addition, fewer Ly6C+ inflammatory monocyte/macrophages (P = 0.002) and dendritic cells (P = 0.017) crossed the BRB following GW10 treatment. In vitro migration assays confirmed that Th17 cells were selectively suppressed by GW559090 in adhering to endothelial monolayers. CONCLUSIONS: This α4ß1 integrin inhibitor may exert a modulatory effect in EAU progression by selectively blocking Th17 cell migration across the blood-retinal barrier without affecting systemic CD4+ T cell subsets. Local α4ß1 integrin-directed inhibition could be clinically relevant in treating a Th17-dominant form of uveitis.

CD4+ T-Cell Plasticity in Non-Infectious Retinal Inflammatory Disease.

Non-infectious uveitis (NIU) is a potentially sight-threatening disease. Effector CD4+ T cells, especially interferon-γ-(IFNγ) producing Th1 cells and interleukin-17-(IL-17) producing Th17 cells, are the major immunopathogenic cells, as demonstrated by adoptive transfer of disease in a model of experimental autoimmune uveitis (EAU). CD4+FoxP3+CD25+ regulatory T cells (Tregs) were known to suppress function of effector CD4+ T cells and contribute to resolution of disease. It has been recently reported that some CD4+ T-cell subsets demonstrate shared phenotypes with another CD4+ T-cell subset, offering the potential for dual function. For example, Th17/Th1 (co-expressing IFNγ and IL-17) cells and Th17/Treg (co-expressing IL-17 and FoxP3) cells have been identified in NIU and EAU. In this review, we have investigated the evidence as to whether these 'plastic CD4+ T cells' are functionally active in uveitis. We conclude that Th17/Th1 cells are generated locally, are resistant to the immunosuppressive effects of steroids, and contribute to early development of EAU. Th17/Treg cells produce IL-17, not IL-10, and act similar to Th17 cells. These cells were considered pathogenic in uveitis. Future studies are needed to better clarify their function, and in the future, these cell subsets may in need to be taken into consideration for designing treatment strategies for disease.

Long-Term Outcomes of Treatment with Biological Agents in Eyes with Refractory, Active, Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis.

PURPOSE: To examine a large cohort of patients treated with biologic agents for active noninfectious intermediate uveitis, posterior uveitis, or panuveitis (NIPPU) and to compare their efficacy and long-term effect. DESIGN: Retrospective, longitudinal study. PARTICIPANTS: Eighty-two patients (156 eyes) with active NIPPU after failure of treatment with corticosteroids and a second-line immunosuppression drug and treated with biologic agents who were treated at Moorfields Eye Hospital between 2001 and 2016. METHODS: Information was gathered from the clinical notes of all patients. MAIN OUTCOME MEASURES: Time to first disease flare, rate of treatment failure, best-corrected visual acuity, and risk factors for treatment failure. RESULTS: Patients were followed on average for 4.7±0.4 years (724 eye-years). All patients demonstrated active uveitis at baseline, and 34 patients (41.5%) demonstrated a coexisting active systemic disease. Control of ocular inflammation was achieved in 136 eyes (87.2%). The average oral prednisolone dose at baseline was 16.4±1.7 mg/day, and by 6 months reduced to 6.5±0.7 mg/day (P < 0.0001), remaining stable for up to 5 years follow-up. Best-corrected visual acuity at baseline was 0.5±0.1 logarithm of the minimum angle of resolution (logMAR), improved to 0.4±0.1 logMAR (P = 0.008) at 3 months, and remained stable during follow-up. After baseline, 42.3% of eyes experienced flares, and the average number of flares reduced from 1.8±0.1 flares/year to 0.6±0.1 flares/year (P < 0.0001). Median time to first flare was 5.4 years (95% confidence interval [CI], 2.2-5.4 years) with a 5-year survival rate of 58.7%. Treatment failed in 37 eyes (23.7%), with a 5-year survival rate of 68.0% and an estimated time to 75% survival of 2.9 years (95% CI, 2.1-4.4 years). The risk for treatment failure was lower when treatment used adalimumab (odds ratio, 0.4; 95% CI, 0.2-0.9; P = 0.03) but was greater when systemic disease also was active at baseline (odds ratio, 3.2; 95% CI, 1.5-7.1; P = 0.004). CONCLUSIONS: Overall, eyes treated with biologic agents after failure of treatment with corticosteroids and a second-line immunosuppression drug experienced satisfactory disease control (87.2%), reduced use of systemic immunosuppression, stable visual acuity, and a 23.7% risk of disease relapse. After multivariate adjustment, older age, treatment with adalimumab (versus infliximab), and inactive concomitant systemic disease were associated with a lower risk of treatment failure.

The prognostic value of total macular external limiting membrane and ellipsoid zone damage for clinical outcome in treatment-resistant neovascular age-related macular degeneration.

PURPOSE: To examine the prognostic value of the extent of damage to the ellipsoid zone (EZ) and external limiting membrane (ELM) in response to the treatment of age-related macular degeneration (AMD) eyes switched from ranibizumab to aflibercept. METHODS: This is a retrospective study of patients with neovascular AMD resistant to ranibizumab defined as having persistent intra- or subretinal fluid on OCT scans despite at least 6-month treatment and switched to aflibercept. Clinical data was collected and quantitative measurements of the area of EZ and ELM damage were obtained, on en-face optical coherence tomography images, at the time of switch to aflibercept (baseline) and up to 6 months of follow-up. RESULTS: The study included 71 eyes (52.1% right eye) of 71 patients. At baseline, there was a correlation between the size of the EZ and ELM damaged area and BCVA (R = -0.39, p = 0.001 and R = -0.47, p < 0.001, respectively). The EZ and ELM damaged areas maintained correlation with BCVA at 6 months (R = -0.28, p = 0.01 and R = -0.39, p = 0.001, respectively). Central retinal thickness did not correlate with BCVA at the time of switch (p = 0.38) or at 6 months (p = 0.36). CONCLUSIONS: The extent of damage to the EZ and ELM correlates with BCVA following a switch in treatment.

Prospective study of morphologic and functional parameter changes post intravitreal therapy for macular edema.

PURPOSE: Retinal sensitivity (RS) can be a valuable indicator of retinal function in response to intravitreal steroid or anti-VEGF treatment in the eyes with diabetic macular edema (DME), macular edema post retinal vein occlusion (RVO), or uveitis. METHODS: This prospective longitudinal study included 68 patients (96 eyes) with macular edema (ME) secondary to diabetes mellitus (42 eyes), uveitis (36 eyes), or RVO (18 eyes). In addition to best corrected visual acuity (BCVA) and retinal thickness, Nidek MP1 microperimetry was used to quantify RS at baseline visit and to look at the mean difference (MD) at 3-6 months and 1-2 years post intravitreal therapy with corticosteroids or anti-VEGF. RESULTS: There was a significant negative correlation between the central RS and BCVA (r = - 0.47, p < 0.001), including DME (r = - 0.42, p = 0.006) and uveitis (r = - 0.60, p < 0.001), but not RVO (r = - 0.37, p = 0.12). At 2-year follow-up, the overall CST was reduced from baseline (MD - 147 µm, 95% C.I - 192 to - 102, p < 0.001) with improved BCVA (MD - 0.12 LogMAR, 95% C.I - 0.23 to - 0.01, p = 0.01), but no improvement in the RS in any of the disorders. Both anti-VEFG and steroid groups showed significant improvement in CST at 2 years from baseline (MD - 101 µm, p = 0.001 and - 167 µm, p < 0.001, respectively) with only improvement in BCVA among anti-VEGF group (MD - 0.16 LogMAR, 95% C.I - 0.26 to - 0.07, p = 0.008). CONCLUSION: The long-term follow-up of ME cases did not show a significant improvement in RS following treatment even with reduced macular thickness at 2-year follow-up.

Outcome and risk of ocular complications of managing children with chronic anterior uveitis with topical rimexolone 1.

PURPOSE: To investigate the efficacy and safety of 1% rimexolone ophthalmic suspension in children with chronic anterior uveitis under real-life conditions in a tertiary center. METHODS: This is a retrospective longitudinal study. Medical records were analyzed at baseline, 1, 3, 6 and 12 months before and after switching to rimexolone for best-corrected visual acuity (BCVA), oral steroid use, number of flares, IOP and anti-glaucoma management. RESULTS: Twenty-four patients (41 eyes) diagnosed with either anterior uveitis (n = 25, 60.0%) or panuveitis (n = 16, 40%) were enrolled. The mean age was 10.5 years (4-16 years). The number of patients requiring oral prednisolone reduced from 8 patients (32.0%) at baseline to 3 patients (20.0%) at 12 months (P < 0.001). Following baseline, the median number of uveitis flares reduced from 2.0 (inter-quartile range (IQR) 1.0-2.75) to 1.0 (IQR 0.0-1.0) compared to the 12 months before baseline (P < 0.001). The mean IOP reduced from baseline (22.0 ± 7.3 mmHg) to 1 month (18.8 ± 8.7 mmHg, P = 0.01) and remained stable up to 12 months (15.9 ± 5.0 mmHg, P < 0.001). Average BCVA, dose of oral prednisolone and anti-glaucoma treatments did not change compared to the baseline. The development for IOP ≥ 30 mmHg was associated with a known corticosteroid response [odds ratio (OR) 6.8, P = 0.003] and a dose > 7.5 mg/day oral prednisolone (OR 4.4, P = 0.033). CONCLUSIONS: Rimexolone 1% ophthalmic suspension is an effective and safe topical steroid for pediatric anterior uveitis.

Viral retinitis: diagnosis and management in the era of biologic immunosuppression: A review.

Necrotising retinitis is a rare ocular infection that historically led to high rates of visual morbidity. While acute retinal necrosis occurs in immunocompetent patients, the majority of cases are associated with immunocompromise such as in cytomegalovirus retinitis and progressive outer retinal necrosis. This review summarises the clinical and diagnostic features, management, and outcomes of herpetic retinitis. Iatrogenic immunosuppression is increasingly being utilised for a wide range of indications, and biologic agents especially so due to their targeted nature. While the intended actions are well-studied, the flow-on effects and complex interaction with host immunity are not well understood. Furthermore, biologics are frequently used concomitantly with other immunosuppressive agents, potentiating the immunodepression. This article reviews the literature on biologic immunosuppression and viral retinitis, and presents an approach to the vulnerable or affected patient. Early identification, prompt and aggressive treatment, and a multidisciplinary approach to managing immunodeficiency are the cornerstones of management.

Risk Factors for Developing Choroidal Neovascular Membrane and Visual Loss in Punctate Inner Choroidopathy.

PURPOSE: To examine a large cohort of subjects with punctate inner choroidopathy (PIC) looking at risk factors for development of choroidal neovascular membrane (CNVM) and visual loss. DESIGN: Retrospective case series. PARTICIPANTS: A total of 203 participants (318 eyes) with PIC seen at Moorfields Eye Hospital between 1996 and 2016. METHODS: Information was gathered from the clinical notes of all subjects identified with PIC. MAIN OUTCOME MEASURES: Development of CNVM, moderate visual loss (MVL) (≤20/50), and severe visual loss (SVL) (≤20/200). RESULTS: Participants were predominantly young (median age at presentation, 32.9 years; interquartile range [IQR], 26.1-42.2), myopic (91.5%), female (87.2%), and white (75.9%). Disease was bilateral at presentation in 115 participants (56.7%), and CNVM was present at presentation in 152 eyes (47.8%). Median follow-up was 8.4 years. New CNVM occurred in 58 eyes (33.5% of affected eyes and 4.3% of initially unaffected eyes). An increased risk of developing CNVM was associated with the presence of a CNVM in the fellow eye (P < 0.0005; hazard ratio [HR], 2.73), and previous oral corticosteroid treatment was associated with halving of the risk of developing CNVM (P = 0.035; HR, 0.45). No difference was observed in visual outcome with oral corticosteroids, but subjects treated with anti-VEGF had better visual outcomes (12-month median visual acuity, logarithm of the minimum angle of resolution [logMAR] 0.00 with anti-VEGF and 0.20 without; P = 0.018). Median best-corrected visual acuity (BCVA) was 20/30 at presentation (IQR, 0.00-0.50) and remained at 20/30 throughout all follow-up periods. Moderate visual loss occurred in 40 eyes (12.6%), with an incidence of 0.01 per eye-year, and SVL occurred in 49 eyes (15.4%), with an incidence of 0.01 per eye-year. Female participants were half as likely as male participants to develop MVL (P = 0.030; HR, 0.448), and participants with CNVM had a higher risk of MVL (P = 0.003; HR, 21.074). CONCLUSIONS: Visual loss is common in subjects with PIC, predominantly secondary to late development of CNVM. Treatment with oral corticosteroids may help to reduce the risk of CNVM development, and anti-VEGF therapy for CNVM was associated with better clinical outcomes.

Long-term effect of cataract phacoemulsification on the inflammation control and clinical outcome in uveitis patients.

IMPORTANCE: Cataract is one of the most common complications associated with uveitis, and is the leading cause of vision loss in these patients. BACKGROUND: The study aimed to evaluate the effect of phacoemulsification on the long-term clinical outcome and inflammation control in uveitis patients. DESIGN: Longitudinal study. PARTICIPANTS: Of 1907 eyes with uveitis, 309 eyes underwent phacoemulsification were compared to a control group of 300 phakic eyes with uveitis. METHOD: The risk of vision loss and macular oedema in pseudophakic eyes were compared to the phakic group. The rates of corticosteroids administration and uveitis relapse were also measured in pseudophakic eyes and compared to preoperative period. MAIN OUTCOME MEASURES: Change in uveitis activity post phacoemulsification by measuring rate of uveitis relapse and use of topical and systemic steroids. Also, to measure the risk of vision loss and macular oedema post surgery. RESULTS: Over a median follow-up time of 6.7 years or 2249 eye-years (EY), pseudophakic eyes had a greater risk of vision loss (hazard ratio [HR] 2.4, CI 1.4 to 4.0; P < 0.001) and macular oedema (HR 2.2, CI 1.4 to 3.4, P < 0.001) compared to the phakic uveitis group. Over 5 years post-surgery, the annual rate of uveitis relapses was less than the same period pre surgery (-1.2, 95% CI -2.0 to -0.2, P = 0.012) with no significant change in the annual rate of using topical and systemic prednisolone >7.5 mg/day. CONCLUSIONS AND RELEVANCE: There was no significant increase in uveitis relapse rate post-phacoemulsification with the use of current prophylactic inflammation control measures.

Predictors of Long-Term Visual Outcome in Intermediate Uveitis.

PURPOSE: To describe factors that predict visual loss and complications in intermediate uveitis. DESIGN: Cross-sectional study. PARTICIPANTS: Subjects with intermediate uveitis were identified from a database of 1254 uveitis patients seen in the clinic of a single consultant (S.L.L.) between 2011 and 2013. METHODS: Information was gathered from the clinical notes of all subjects examined in clinic. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), moderate visual loss (MVL; ≤20/50), severe visual loss (SVL; ≤20/200). RESULTS: Three hundred and five subjects (550 eyes) were included in the study, comprising 24.3% of subjects seen in clinic. Mean (± standard deviation) age at diagnosis was 40.9±16.9 years, and 64.6% of subjects were female. Median follow-up was 8.2 years (mean, 9.7 years, 5452 eye-years). Systemic diagnosis was made in 36.1% of patients, with sarcoidosis (22.6%) and multiple sclerosis (4.6%) the most frequent systemic associations. Median BCVA was 20/30 (mean logarithm of the minimum angle of resolution [logMAR] 0.26±0.38, n = 550 eyes) at presentation, 20/30 (mean logMAR 0.22±0.42, n = 430) at 5 years, and 20/30 (mean logMAR 0.23±0.46, n = 260) at 10 years. Macular edema was observed in 224 eyes (40.7%) and was associated with idiopathic disease (P = 0.001) and diabetes (P = 0.001). Topical therapy was used in 82.7%, and 34.2% received local injections of corticosteroids. A total of 50.5% required oral steroids and 13.8% required second-line immunosuppression. Subjects with a diagnosis of sarcoidosis were less likely to require a second-line agent (4.3% vs. 16.2%, P = 0.011). On multivariate analysis, visual acuity at referral, retinal pigment epithelial atrophy, and macular scarring were associated with increased risk of MVL; and visual acuity at referral, local therapy, macular scarring, retinal detachment, and hypotony and phthisis were associated with increased risk of SVL. CONCLUSIONS: Intermediate uveitis has a long disease course with frequent complications and often requires systemic treatment. Despite this, most subjects are still able to achieve good long-term visual outcomes.

Difference in glaucoma progression between the first and second eye after consecutive bilateral glaucoma surgery in patients with bilateral uveitic glaucoma.

PURPOSE: To determine whether the second eyes (SE) of patients with bilateral uveitic glaucoma undergoing filtration surgery have more glaucomatous progression in terms of visual acuity, visual field (VF) and optic nerve changes compared to the first eyes (FE). METHODS: This retrospective study analysed data of 60 eyes from 30 patients with bilateral uveitic glaucoma who had undergone glaucoma surgery in both eyes on separate occasions. Humphrey VF progression was assessed using the Progressor software. RESULTS: The pre-operative IOP between the FE (43.1 ± 7.7 mmHg) and SE (40 ± 8.7 mmHg) was not statistically significant (p = 0.15). IOP reduction was greater in the FE (64 %) than SE (59.7 %) post-operatively, but the mean IOP at the final visit in the FE (12.3 ± 3.9 mmHg) and SE (14.5 ± 7 mmHg) was not statistically different (p = 0.2). There was no significant change in mean logMAR readings pre and post-operatively (0.45 ± 0.6 vs 0.37 ± 0.6, p = 0.4) or between the FE and SE. The number of SE with CDR > 0.7 increased by 23 % compared to the FE. From 23 available VFs, five SE (21.7 %) progressed at a median of five locations (range 1-11 points) with a mean local slope reduction of 1.74 ± 0.45 dB/year (range -2.39 to -1.26), whereas only one FE progressed. However, there was no significant difference between mean global rate of progression between the FE (-0.9 ± 1.6 dB/year) and SE (-0.76 ± 2.1 dB/year, p = 0.17) in the Humphrey VF. CONCLUSION: In eyes with bilateral uveitic glaucoma requiring glaucoma surgery, the SEs had more progressed points on VF and glaucomatous disc progression compared to FEs at the final visit.

Clinical and Imaging Features of Lacrimal Gland Involvement in Granulomatosis with Polyangiitis.

PURPOSE: Lacrimal gland involvement in granulomatosis with polyangiitis (GPA) commonly accompanies orbital disease, but occasionally may be the sole presentation preceding any other organ manifestation or systemic disease. Diagnosis of orbital GPA, especially in patients with lacrimal involvement as the initial presentation, can be difficult because of nonspecific clinical features and lack of diagnostic specificity on histologic and antineutrophilic cytoplasmic antibody (ANCA) testing. Orbital GPA can be associated with a high morbidity from potential visual loss or rapid progression of latent systemic disease, making early diagnosis important. The purpose of this study was to describe the clinical and imaging features of patients with lacrimal gland involvement secondary to GPA and to compare them with those of other orbital inflammatory conditions in the lacrimal gland fossa. DESIGN: Retrospective, noninterventional comparative case series. PARTICIPANTS: Two hundred forty-seven patients who had undergone orbital biopsy over a 21-year period were identified from the Institute of Ophthalmology Pathology database. Sixty-nine patients were found to have orbital inflammatory disease with lacrimal gland involvement, of whom 7 had a final diagnosis of GPA. METHODS: Clinical and imaging features of patients with GPA were analyzed and compared with those of the non-GPA group. MAIN OUTCOME MEASURES: Features associated with GPA. RESULTS: The median age at presentation for GPA patients was 30 years (mean ± standard deviation, 36.7±16.7 years; range, 14-57 years). The interval from presentation to definitive diagnosis of GPA ranged from 3 to 20 months (mean, 12.1 months; median, 12 months). Sinonasal involvement was demonstrated in 43% and bony changes were demonstrated in 29% of patients with GPA. A higher proportion of patients with GPA demonstrated sinonasal involvement (P = 0.011) and bony destruction (P = 0.048) compared with non-GPA patients. CONCLUSIONS: Associated sinonasal involvement and bony changes on imaging are highly suggestive of GPA and should prompt a full diagnostic workup. A high index of suspicion should be maintained, with repeated ANCA testing, biopsy, and imaging where indicated, especially in the younger age group.

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 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.

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.

Clinical and imaging features predictive of orbital granulomatosis with polyangiitis and the risk of systemic involvement.

OBJECTIVE: Granulomatosis with polyangiitis (GPA), previously Wegener's granulomatosis, requires prompt diagnosis and systemic review to exclude life-threatening disease. However, early diagnosis of orbital GPA may be difficult because anti-neutrophil cytoplasmic antibody (ANCA) and anti-PR3 antibody screening can be negative at presentation and orbital biopsies taken for diagnosis may not show the classic features of GPA. This study was designed to compare GPA with other causes of orbital inflammation and to identify the presenting clinical and imaging features most likely to predict GPA and its systemic spread. DESIGN: Retrospective noninterventional comparative case series. PARTICIPANTS: A total of 247 patients who had undergone orbital biopsies for clinical presentations with orbital inflammation were identified from the Institute of Ophthalmology pathology database. METHODS: Patients were divided into GPA and non-GPA groups on the basis of their final clinical diagnosis. Clinical and imaging features of these 2 groups were compared to determine those predictive of GPA, and patients with GPA also had long-term evaluation for systemic involvement. MAIN OUTCOME MEASURES: A diagnosis of orbital GPA and development of systemic GPA were the main outcome measures. RESULTS: Features highly suggestive of GPA were sinonasal symptoms, sinonasal changes, or paranasal bone erosion on imaging (P < 0.001). Bony erosion was independent of ANCA status or systemic involvement. Twenty-two percent of patients (8/37) with GPA had evidence of systemic involvement at presentation, and no patient presenting with solely orbital GPA developed later systemic disease over a median follow-up of 2.7 years. CONCLUSIONS: A high index of suspicion should be maintained for GPA when a patient presents with an orbital mass and sinonasal symptoms or imaging shows sinonasal involvement or paranasal bone erosion. No patient with solely orbital GPA involvement at presentation developed systemic disease, suggesting that orbital GPA can remain localized in the long-term.