[CLINICAL MANIFESTATIONS OF AUTOIMMUNE DISEASES].

INTRODUCTION: Ocular inflammation, uveitis, represents over 40 distinct diseases, caused by infectious or non-infectious etiologies. Non-infectious uveitis may be related to systemic autoimmune diseases. Most uveitis patients are of working age, and prolonged disease may affect their independence and ability to work. Uveitis has various clinical manifestations and may result in the development of ocular complications and vision loss. Uveitis accounts for 10-15% of blindness in the developed world. Autoimmune diseases are increasing globally and often involve the eyes. Most cases occur in young active people and therefore any ocular changes have a longer effect. Symptoms may be mild but they might be severe, even blindness. It accounts for 10% to 15% of all causes of blindness among people of working age in the developed world. OBJECTIVES: To describe the ocular manifestation of uveitis related to systemic autoimmune diseases. We will describe ocular signs related to the disease and discuss the treatment approach to prevent the development of ocular complications and vision loss. METHODS: Review of clinical findings and treatment approach to non-infectious uveitis. CONCLUSIONS: Ocular involvement is commonly found in many autoimmune diseases. The severity of ocular disease varies between cases and complications may result in vision loss. Early diagnosis and treatment may prevent the development of ocular complications, maintaining visual acuity and patient independence.

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.

Association between Vaccination with the BNT162b2 mRNA Coronavirus Disease 2019 Vaccine and Noninfectious Uveitis: A Population-Based Study.

PURPOSE: To assess the association between BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine and the risk of active noninfectious uveitis (NIU). DESIGN: Retrospective, population-based study. PARTICIPANTS: Two million six hundred two thousand five hundred fifty-seven people who received the first vaccine dose between December 20, 2020, and April 30, 2021, and 2 441 719 people who received the second vaccine dose between January 10, 2021, and April 30, 2021. METHODS: Events of active NIU were included if they occurred within 21 days after either vaccine dose. Active NIU was defined as newly active or worsening ocular inflammation requiring initiation or increase in local or systemic corticosteroids. Observed cases were compared with the expected number, based on the experience of the population in 2019. MAIN OUTCOME MEASURES: Age- and sex-adjusted standardized incidence ratios (SIRs) and attributable risks after BNT126b2 vaccination. RESULTS: Overall, 100 and 88 events of active NIU were recorded within 21 days after the first and second vaccine doses, respectively. Using the experience of the population in 2019 as a reference, after the first dose, the estimated age- and sex-adjusted SIR was 1.41 (95% confidence interval [CI], 1.15-1.71) along with a 21-day attributable risk of 1.12 cases per 100 000 vaccinees. After the second dose, the SIR was 1.31 (95% CI, 1.05-1.62), with an estimated attributable risk of 0.86 cases per 100 000 vaccinees. Anterior uveitis was the most common site of inflammation, occurring in 90.96% of eyes, and idiopathic uveitis was the most common cause (56.38%). CONCLUSIONS: This study suggests that the BNT162b2 mRNA COVID-19 vaccine may be associated with an increased risk of active NIU. However, considering the small effect size and study limitations, this study does not provide proof for a cause-and-effect relationship. The small estimated attributable risks suggest that the impact on public health is relatively minor.

Evaluation of a self-imaging SD-OCT system designed for remote home monitoring.

PURPOSE: To compare identification rates of retinal fluid of the Notal Vision Home Optical Coherence Tomography (OCT) device (NVHO) when used by people with age-related macular degeneration (AMD) to those captured by a commercial OCT. METHODS: Prospective, cross-sectional study where patients underwent commercial OCT imaging followed by self-imaging with either the NVHO 2.5 or the NVHO 3 in clinic setting. Outcomes included patients' ability to acquire analyzable OCT images with the NVHO and to compare those with commercial images. RESULTS: Successful images were acquired with the NVHO 2.5 in 469/531 eyes (88%) in 264/290 subjects (91%) with the mean (SD) age of 78.8 (8.8); 153 (58%) were female with median visual acuity (VA) of 20/40. In the NVHO 3 cohort, 69 eyes of 45 subjects (93%) completed the self-imaging. Higher rates of successful imaging were found in eyes with VA ≥ 20/320. Positive percent agreement/negative percent agreement for detecting the presence of subretinal and/or intraretinal fluid when reviewing for fluid in three repeated volume scans were 97%/95%, respectively for the NVHO v3. CONCLUSION: Self-testing with the NVHO can produce high quality images suitable for fluid identification by human graders, suggesting the device may be able to complement standard-of-care clinical assessments and treatments.

[OCULAR MANIFESTATIONS IN BEHÇET DISEASE].

INTRODUCTION: Ocular involvement in Behçet disease occurs is most patients and can be the presenting organ. Intra-ocular inflammation (uveitis) related to Behçet disease is mainly a panuveitis including an occlusive retinal vasculitis. Recurrent inflammation can result in the development of ocular complications, including macular edema and retinal neovascularization, with up to a quarter of eyes developing vision loss. Diagnosis is based on clinical ophthalmic findings and ocular imaging including retinal fluorescein angiography and optical coherence tomography. Early diagnosis and treatment may prevent the development of ocular complications and vision loss. Treatment is based primarily on systemic corticosteroids and 2nd-line immunosuppressive agents, particularly anti-tumor necrosis factor α agents. Extensive treatment, prevention of relapses and complications can result in long term stable vision.

Seven-Year Outcomes of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial and Follow-up Study Results.

PURPOSE: To evaluate the long-term outcomes of uveitic macular edema (ME). DESIGN: Longitudinal follow-up of a cohort of participants in a randomized clinical trial. PARTICIPANTS: A total of 248 eyes of 177 participants with uveitic ME enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. METHODS: OCT measurements, taken at baseline and annually, were graded by reading center graders masked to clinical data. Macular edema was defined as a center macular thickness (CMT) ≥240 µm on time-domain OCT or time-domain OCT equivalent. Resolution of ME was defined as normalization of macular thickness on OCT. Relapse of ME was defined as increase in macular thickness to ≥240 µm in an eye that previously had resolution. Visual acuity was measured at each visit with logarithmic visual acuity charts. MAIN OUTCOME MEASURES: Resolution and relapse of ME. Visual acuity. RESULTS: Among 227 eyes with ME followed ≥1 year, the cumulative percent of eyes with ME resolving at any point during 7 years was 94% (95% confidence interval [CI], 89-97). Epiretinal membranes on OCT were associated with a lower likelihood of ME resolution (hazard ratio [HR], 0.74; 95% CI, 0.55-1.01; P = 0.05). Among 177 eyes with resolved ME, the cumulative percent with relapse within 7 years was 43% (95% CI, 32-51). Eyes in which ME resolved gained a mean of 6.24 letters (95% CI, 4.40-8.09; P < 0.001) compared with eyes that remained free from ME during the 1-year follow-up intervals, whereas eyes in which ME did not resolve experienced no gain in vision (mean change -1.30 letters; 95% CI, -2.70 to 0.09; P = 0.065), and eyes that developed ME during the year (incident or relapsed) experienced a mean loss of -8.65 letters (95% CI, -11.5 to -5.84, P < 0.001). CONCLUSIONS: Given sufficient time and treatment, nearly all uveitic ME resolves, but episodes of relapse were common. Visual acuity results were better among eyes with resolved ME, suggesting that control of inflammation and resolution of ME might be visually relevant treatment targets.

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.

The effect of anti-tumor necrosis factor alpha agents on the outcome in pediatric uveitis of diverse etiologies.

PURPOSE: This study aimed to report the clinical outcome of children with uveitis treated with anti-tumor necrosis factor alpha (TNF-α) agents. METHODS: This included a retrospective cohort study. Children with uveitis treated with infliximab or adalimumab in 2008-2014 at five dedicated uveitis clinics were identified by database search. Their medical records were reviewed for demographic data, clinical presentation, ocular complications, and visual outcome. Systemic side effects and the steroid-sparing effect of treatment were documented. RESULTS: The cohort included 24 patients (43 eyes) of whom 14 received infliximab and 10 received adalimumab after failing conventional immunosuppression therapy. Mean age was 9.3 ± 4.0 years. The most common diagnosis was juvenile idiopathic arthritis-related uveitis (n = 10), followed by Behçet's disease (n = 4), sarcoidosis (n = 1), and ankylosing spondylitis (n = 1); eight had idiopathic uveitis. Ocular manifestations included panuveitis in 20 eyes (46.5%), chronic anterior uveitis in 19 (44.2%), and intermediate uveitis in 4 (9.3%). The duration of biologic treatment ranged from 6 to 72 months. During the 12 months prior to biologic treatment, while on conventional immunosuppressive therapy, mean visual acuity deteriorated from 0.22 to 0.45 logMAR, with a trend of recovery to 0.25 at 3 months after initiation of biologic treatment, remaining stable thereafter. A full corticosteroid-sparing effect was demonstrated in 16 of the 19 patients (84.2%) for whom data were available. Treatment was well tolerated. CONCLUSIONS: Treatment of pediatric uveitis with anti-TNF-α agents may improve outcome while providing steroid-sparing effect, when conventional immunosuppression fails. The role of anti-TNF-α agents as first-line treatment should be further investigated in controlled prospective clinical trials.

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.

Outcome of Treatment of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial 2-Year Results.

PURPOSE: To evaluate the 2-year outcomes of uveitic macular edema. DESIGN: Longitudinal follow-up of a randomized cohort. PARTICIPANTS: At baseline, 148 eyes of 117 patients enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial had macular edema, and 134 eyes of 108 patients completed 2-year follow-up. METHODS: Patients enrolled in the study were randomized to either systemic immunosuppression or intravitreal fluocinolone acetonide implant therapy. Macular edema was defined as thickening of the retina (center point thickness≥240 µm) on time-domain optical coherence tomography (OCT) of macula. MAIN OUTCOME MEASURES: Improvement in macular edema (≥20% reduction in central point thickness on OCT), resolution of macular edema (normalization of thickness on OCT), and best-corrected visual acuity (BCVA). RESULTS: Between randomization and 2-years' follow-up, 62% and 25% of eyes in the systemic and implant groups, respectively, received at least 1 supplemental regional corticosteroid injection. By 2-years' follow-up, macular edema improved in 71% of eyes and resolved in 60%. There were no differences between treatment groups in the proportion of eyes with macular edema improving (systemic therapy vs. implant, 65% vs. 77%; P=0.20) and resolving (52% vs. 68%; P=0.28), but eyes randomized to implant had more improvement in macular thickness (median decrease of 180 vs. 109 µm in the systemic therapy group; P=0.04). Eyes with baseline fluorescein angiographic leakage were more likely to improve than those without (76% vs. 58%; P=0.03). Overall, there was a mean 5-letter (1 line) improvement in BCVA at 2 years. Mean changes in BCVA from baseline at 2 years by macular edema response status were: resolution, +10 letters; improvement without resolution, +10 letters (P=0.92); little to no change, 6 letters (P=0.19); and worsening, -16 letters (worsening acuity; P=0.0003). CONCLUSIONS: About two thirds of eyes with uveitic macular edema were observed to experience improvement in the edema and visual acuity with implant or systemic treatment. Fluocinolone acetonide implant therapy was associated with a greater quantitative improvement in thickness. Fluorescein angiography leakage was associated with a greater likelihood of improvement in macular edema.

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.