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The integration of artificial intelligence (AI) with healthcare has opened new avenues for diagnosing, treating, and managing medical conditions with remarkable precision. Uveitis, a diverse group of rare eye conditions characterized by inflammation of the uveal tract, exemplifies the complexities in ophthalmology due to its varied causes, clinical presentations, and responses to treatments. Uveitis, if not managed promptly and effectively, can lead to significant visual impairment. However, its management requires specialized knowledge, which is often lacking, particularly in regions with limited access to health services. AI's capabilities in pattern recognition, data analysis, and predictive modelling offer significant potential to revolutionize uveitis management. AI can classify disease etiologies, analyze multimodal imaging data, predict outcomes, and identify new therapeutic targets. However, transforming these AI models into clinical applications and meeting patient expectations involves overcoming challenges like acquiring extensive, annotated datasets, ensuring algorithmic transparency, and validating these models in real-world settings. This review delves into the complexities of uveitis and the current AI landscape, discussing the development, opportunities, and challenges of AI from theoretical models to bedside application. It also examines the epidemiology of uveitis, the global shortage of uveitis specialists, and the disease's socioeconomic impacts, underlining the critical need for AI-driven approaches. Furthermore, it explores the integration of AI in diagnostic imaging and future directions in ophthalmology, aiming to highlight emerging trends that could transform management of a patient with uveitis and suggesting collaborative efforts to enhance AI applications in clinical practice.
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Purpose: To report the design of FL uorometholone as A djunctive ME dical Therapy for TT Surgery (FLAME) Trial. Design: Parallel design, double-masked, placebo-controlled clinical trial with 1:1 randomization to fluorometholone 0.1% eyedrops twice daily or placebo twice daily for four weeks in eyes undergoing trachomatous trichiasis (TT) surgery; assessing the efficacy, safety, and cost-effectiveness of fluorometholone 0.1% in preventing recurrent postoperative trichiasis. Methods: Up to 2500 eligible persons with trachomatous trichiasis (TT) undergoing lid rotation surgery will be enrolled in Jimma zone, Ethiopia. Participants, surgeons, study field staff, and study supervisors leading operational aspects of the trial are masked to treatment assignment. Randomization is stratified by surgeon, which simultaneously stratifies by the district. The study visits are at baseline/enrollment, at four-week post-enrollment, six months, and one year (study exit). The primary outcome is cumulative one-year postoperative TT (PTT) incidence, defined as: ≥1 lashes touching the globe, evidence of epilation, and/or repeat TT surgery. Secondary postoperative outcomes include number of trichiatic lashes, location thereof (touching the cornea or not), evidence of post-operative epilation, entropion, changes in corneal opacity, IOP elevation, need for cataract surgery, visual acuity change from baseline, eyelid contour abnormality, granuloma, eyelid closure defect, and occurrence of adverse events. Health economic analyses center on calculating the incremental cost per case of PTT avoided by fluorometholone treatment. Conclusion: The FLAME Trial is designed to provide evidence of the efficacy, safety, and cost-effectiveness of adjunctive topical peri-/postoperative fluorometholone 0.1% therapy with trichiasis surgery, which is hypothesized to reduce the risk of recurrent trichiasis while being acceptably safe. Trial Registration: ClinicalTrials.gov # NCT04149210.
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PURPOSE: To evaluate the incidence, remission, and relapse of post-surgical cystoid macular edema (PCME) following cataract surgery in inflammatory eye disease. METHODS: A total of 1859 eyes that had no visually significant macular edema prior to cataract surgery while under tertiary uveitis management were included. Standardized retrospective chart review was used to gather clinical data. Univariable and multivariable logistic regression models with adjustment for inter-eye correlations were performed. RESULTS: PCME causing VA 20/50 or worse was reported in 286 eyes (15%) within 6 months of surgery. Adults age 18-64 years as compared to children (adjusted odds ratio [aOR] = 2.42, for ages 18 to 44 years and aOR = 1.93 for ages 45 to 64 years, overall P = .02); concurrent use of systemic immunosuppression (conventional aOR 1.53 and biologics aOR = 2.68, overall P = .0095); preoperative VA 20/50 or worse (overall P < .0001); cataract surgery performed before 2000 (overall P = .03) and PMCE in fellow eye (aOR = 3.04, P = .0004) were associated with development of PCME within 6 months of cataract surgery. PCME resolution was seen in 81% of eyes at 12 months and 91% of eyes at 24 months. CME relapse was seen in 12% eyes at 12 months and 19% eyes at 24 months. CONCLUSIONS: PCME occurs frequently in uveitic eyes undergoing cataract surgery; however, most resolve within a year. CME recurrences likely are due to the underlying disease process and not relapses of PCME.
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PURPOSE: This study aims to understand the practice patterns among ophthalmologists in North America who manage patients with acute, non-infectious anterior uveitis. METHODS: An eight-question survey was designed to elucidate the practice patterns of ophthalmologists across various geographic locations and practice settings regarding the management of anterior uveitis. This survey was distributed via the American Uveitis Society and Young Uveitis Specialists email listserv to ophthalmologists who self-identify as uveitis specialists and have a patient population that is at least 30% uveitis. RESULTS: A total of 102 responses were received and analyzed (37% response rate). Respondents practiced predominantly in North America, and 40% had received subspecialty training in uveitis. All respondents chose topical corticosteroid therapy as first-line treatment for acute, unilateral, or bilateral non-infectious idiopathic anterior uveitis. The most common initial frequency for prednisolone acetate administration was six times/day while the patient was awake (29.7%) and patients are typically seen in follow-up within a week (75% of respondents). If there is a lack of treatment response within 2-3 weeks with the initial topical treatment, 42 respondents (41.2%) chose to switch to difluprednate eye drops and 29 (28.4%) recommended switching to oral prednisone. CONCLUSION: Our results show that topical corticosteroid, most frequently prednisolone acetate 1%, is the treatment of choice for patients with acute noninfectious anterior uveitis. Reported initial medication dosing and follow-up care approaches are highly variable, which suggests heterogeneity in practice patterns. Further research on the optimal initial dosing is needed.
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OBJECTIVE: To evaluate the incidence of visually significant posterior capsule opacification (PCO with visual acuity ≤20/50) and the incidence of Nd:YAG laser capsulotomy in the year following cataract surgery for uveitic eyes. METHOD: Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study using a standardized chart review process. RESULTS: Among 1,855 uveitic eyes of 1,370 patients who had undergone cataract surgery, visually significant PCO occurred in 297 eyes (16%), and YAG laser capsulotomy was done in 407 eyes (22%) within the first year following surgery. Higher odds of developing 20/50 visual acuity attributed to PCO were noted in children and young adults compared with adults older than 65 years of age (overall pâ¯=â¯0.03). Poorer preoperative visual acuity (overall pâ¯=â¯0.0069) and postoperative inflammation (odds ratio [OR]â¯=â¯1.83; 95% CI, 1.37-2.45; p < 0.0001) were associated with PCO incidence. In multivariable analysis, risk factors for YAG laser capsulotomy were younger age groups compared with those older than 65 years of age at the time of surgery (adjusted OR [aOR]â¯=â¯1.90-2.24; 95% CI, 1.90-2.24; overall pâ¯=â¯0.0007), female sex (aORâ¯=â¯1.37; 95% CI, 1.03-1.82; pâ¯=â¯0.03), postoperative active inflammation (aORâ¯=â¯165; 95% CI, 1.27-2.16; overall p < 0.0001), extracapsular cataract extraction compared with phacoemulsification (aORâ¯=â¯1.70; 95% CI, 1.17-2.47; overall p < 0.0001), and insertion of an intraocular lens (aORâ¯=â¯4.60; 95% CI, -2.29-9.25; p < 0.0001). Black race was associated with lower YAG laser capsulotomy incidence than Whites (aORâ¯=â¯0.36; 95% CI, 0.24-0.52; overall p < 0.0001). CONCLUSIONS: Vision-reducing (≤20/50) PCO is common, occurring in about one sixth of uveitic eyes within 1 year of cataract surgery; a higher number (22%) of eyes underwent YAG laser capsulotomy within the first year. Age and postoperative inflammation following cataract surgery are the variables most associated with the incidence of visually significant PCO and YAG laser capsulotomy.
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Infectious diseases affecting the eye often cause unilateral or asymmetric visual loss in children and people of working age. This group of conditions includes viral, bacterial, fungal and parasitic diseases, both common and rare presentations which, in aggregate, may account for a significant portion of the global visual burden. Diagnosis is frequently challenging even in specialist centres, and many disease presentations are highly regional. In an age of globalisation, an understanding of the various modes of transmission and the geographic distribution of infections can be instructive to clinicians. The impact of eye infections on global disability is currently not sufficiently captured in global prevalence studies on visual impairment and blindness, which focus on bilateral disease in the over-50s. Moreover, in many cases it is hard to differentiate between infectious and immune-mediated diseases. Since infectious eye diseases can be preventable and frequently affect younger people, we argue that in future prevalence studies they should be considered as a separate category, including estimates of disability-adjusted life years (DALY) as a measure of overall disease burden. Numbers of ocular infections are uniquely affected by outbreaks as well as endemic transmission, and their control frequently relies on collaborative partnerships that go well beyond the remit of ophthalmology, encompassing domains as various as vaccination, antibiotic development, individual healthcare, vector control, mass drug administration, food supplementation, environmental and food hygiene, epidemiological mapping, and many more. Moreover, the anticipated impacts of global warming, conflict, food poverty, urbanisation and environmental degradation are likely to magnify their importance. While remote telemedicine can be a useful aide in the diagnosis of these conditions in resource-poor areas, enhanced global reporting networks and artificial intelligence systems may ultimately be required for disease surveillance and monitoring.
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Infecciones del Ojo , Humanos , Infecciones del Ojo/epidemiología , Infecciones del Ojo/diagnóstico , Salud Global , PrevalenciaRESUMEN
PURPOSE: To evaluate the long-term visual acuity (VA) outcome of cataract surgery in inflammatory eye disease. SETTING: Tertiary care academic centres. DESIGN: Multicentre retrospective cohort study. METHODS: A total of 1741 patients with non-infectious inflammatory eye disease (2382 eyes) who underwent cataract surgery while under tertiary uveitis management were included. Standardised chart review was used to gather clinical data. Multivariable logistic regression models with adjustment for intereye correlations were performed to evaluate the prognostic factors for VA outcomes. Main outcome measure was VA after cataract surgery. RESULTS: Uveitic eyes independent of anatomical location showed improved VA from baseline (mean 20/200) to within 3 months (mean 20/63) of cataract surgery and maintained through at least 5 years of follow-up (mean 20/63). Eyes that achieved 20/40 or better VA at 1 year were more likely to have scleritis (OR=1.34, p<0.0001) or anterior uveitis (OR=2.2, p<0.0001), VA 20/50 to 20/80 (OR 4.76 as compared with worse than 20/200, p<0.0001) preoperatively, inactive uveitis (OR=1.49, p=0.03), have undergone phacoemulsification (OR=1.45 as compared with extracapsular cataract extraction, p=0.04) or have had intraocular lens placement (OR=2.13, p=0.01). Adults had better VA immediately after surgery, with only 39% (57/146) paediatric eyes at 20/40 or better at 1 year. CONCLUSIONS: Our results suggest that adult and paediatric eyes with uveitis typically have improved VA following cataract surgery and remain stable thereafter for at least 5 years.
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Extracción de Catarata , Catarata , Enfermedades de la Conjuntiva , Facoemulsificación , Uveítis , Adulto , Humanos , Niño , Estudios Retrospectivos , Catarata/complicaciones , Resultado del Tratamiento , Extracción de Catarata/métodos , Agudeza Visual , Uveítis/complicaciones , Uveítis/diagnóstico , Uveítis/cirugía , Trastornos de la VisiónRESUMEN
PURPOSE: To investigate the demographic and clinical characteristics of patients with sympathetic ophthalmia (SO) and define the risk factors for its incidence following trauma and ophthalmic procedures. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients in the American Academy of Ophthalmology's (Academy) IRIS Registry (Intelligent Research in Sight) who were (n=1523) or were not diagnosed with SO following a documented procedure or trauma between January 1, 2013, and December 31, 2019. METHODS: Multiple demographic and clinical factors were collected, descriptive statistics and prevalence were calculated, and multivariate linear regression models were fit to the data. MAIN OUTCOME MEASURES: Prevalence of SO, demographic and clinical characteristics, and beta coefficient (ß) estimates of demographic and clinical characteristics impacting time to SO onset after procedure (Procedure Only cohort) or trauma (Trauma cohort). RESULTS: Of 65,348,409 distinct IRIS Registry patients, 1523 (0.0023%) were diagnosed with SO between 2013 and 2019, and also had a documented preceding trauma or procedure. Of these, 927 (60.87%) were female, 1336 (87.72%) belonged to the Procedure Only cohort, and 187 (12.28%) belonged to the Trauma cohort. The prevalence of SO after trauma was 0.0207%, whereas after procedures it was 0.0124%. The highest risk of procedure-related SO was seen in patients with history of "other anterior segment" (0.122%) followed by glaucoma (0.066%) procedures, whereas the lowest prevalence was noted with cataract surgeries (0.011%). The average time to onset of SO across both cohorts combined was 527.44 (±715.60) days, with statistically significant differences between the 2 cohorts (P < .001). On average, the time to onset from inciting event to SO was shorter with increasing age, by 9.02 (95% CI: -11.96, -6.08) days for every 1-year increase. CONCLUSIONS: SO following trauma and ophthalmic procedure is potentially rarer than previously reported, as measured in this large ophthalmic medical record database. Female sex may be a risk factor for SO. Older age may be a risk factor for quicker onset. These findings can guide clinical decision-making and management.
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Glaucoma , Oftalmía Simpática , Humanos , Femenino , Estados Unidos/epidemiología , Recién Nacido , Masculino , Estudios Retrospectivos , Oftalmía Simpática/diagnóstico , Oftalmía Simpática/epidemiología , Glaucoma/complicaciones , Sistema de Registros , Factores de RiesgoRESUMEN
AIMS: To present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide. METHODS: A two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting ≥75% of agreement or IQR ≤ 1 when a Likert scale is used. RESULTS: Unilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints. CONCLUSIONS: Consensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts.
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Herpes Simple , Herpes Zóster Oftálmico , Herpes Zóster , Uveítis Anterior , Uveítis , Humanos , Herpesvirus Humano 3 , Simplexvirus , Herpes Zóster Oftálmico/diagnóstico , Herpes Zóster Oftálmico/tratamiento farmacológico , Uveítis Anterior/diagnóstico , Uveítis Anterior/tratamiento farmacológico , Atrofia , Herpes Simple/diagnóstico , Herpes Simple/tratamiento farmacológicoRESUMEN
AIMS: To present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide. METHODS: A two-round modified Delphi survey with masking of the study team was performed. Based on experience and expertise, 100 international uveitis specialists from 21 countries were invited to participate in the survey. Variation in the diagnostic approaches and preferred management of CMV AU was captured using an online survey platform. RESULTS: Seventy-five experts completed both surveys. Fifty-five of the 75 experts (73.3%) would always perform diagnostic aqueous tap in suspected CMV AU cases. Consensus was achieved for starting topical antiviral treatment (85% of experts). About half of the experts (48%) would only commence systemic antiviral treatment for severe, prolonged, or atypical presentation. The preferred specific route was ganciclovir gel 0.15% for topical treatment (selected by 70% of experts) and oral valganciclovir for systemic treatment (78% of experts). The majority of experts (77%) would commence treatment with topical corticosteroid four times daily for one to two weeks along with antiviral coverage, with subsequent adjustment depending on the clinical response. Prednisolone acetate 1% was the drug of choice (opted by 70% of experts). Long-term maintenance treatment (up to 12 months) can be considered for chronic course of inflammation (88% of experts) and those with at least 2 episodes of CMV AU within a year (75-88% of experts). CONCLUSIONS: Preferred management practices for CMV AU vary widely. Further research is necessary to refine diagnosis and management and provide higher-level evidence.
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Infecciones por Citomegalovirus , Uveítis Anterior , Humanos , Citomegalovirus , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/tratamiento farmacológico , Humor Acuoso , Ganciclovir/uso terapéutico , Antivirales/uso terapéutico , Uveítis Anterior/diagnóstico , Uveítis Anterior/tratamiento farmacológicoRESUMEN
Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly from retinal detachment. The antiviral treatment approach for acute retinal necrosis varies as there are no established guidelines. We summarize the outcomes of acute retinal necrosis with available antiviral treatments. Electronic searches were conducted in PubMed/MEDLINE, EMBASE, Scopus, and Google Scholar for interventional and observational studies. Meta-analysis was performed to evaluate the pooled proportion of the predefined selected outcomes. This study was registered in PROSPERO (CRD42022320987). Thirty-four studies with a total of 963 participants and 1,090 eyes were included in the final analysis. The estimated varicella-zoster virus and herpes simplex virus polymerase chain reaction-positive cases were 63% (95% CI: 55-71%) and 35% (95% CI: 28-42%), respectively. The 3 main antiviral treatment approaches identified were oral antivirals alone, intravenous antivirals alone, and a combination of systemic (oral or intravenous) and intravitreal antivirals. The overall pooled estimated proportions of visual acuity improvement, recurrence, and retinal detachment were 37% (95% CI: 27-47%), 14% (95% CI: 8-21%), and 43% (95% CI: 38-50%), respectively. Patients treated with systemic and intravitreal antivirals showed a trend towards better visual outcomes than those treated with systemic antivirals (oral or intravenous) alone, even though this analysis was not statistically significant (test for subgroup differences P = 0.83).
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Infecciones Virales del Ojo , Desprendimiento de Retina , Síndrome de Necrosis Retiniana Aguda , Humanos , Síndrome de Necrosis Retiniana Aguda/tratamiento farmacológico , Antivirales/uso terapéutico , Aciclovir/uso terapéutico , Infecciones Virales del Ojo/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
PURPOSE: To assess the diagnostic performance of two chatbots, ChatGPT and Glass, in uveitis diagnosis compared to renowned uveitis specialists, and evaluate clinicians' perception about utilizing artificial intelligence (AI) in ophthalmology practice. METHODS: Six cases were presented to uveitis experts, ChatGPT (version 3.5 and 4.0) and Glass 1.0, and diagnostic accuracy was analyzed. Additionally, a survey about the emotions, confidence in utilizing AI-based tools, and the likelihood of incorporating such tools in clinical practice was done. RESULTS: Uveitis experts accurately diagnosed all cases (100%), while ChatGPT achieved a diagnostic success rate of 66% and Glass 1.0 achieved 33%. Most attendees felt excited or optimistic about utilizing AI in ophthalmology practice. Older age and high level of education were positively correlated with increased inclination to adopt AI-based tools. CONCLUSIONS: ChatGPT demonstrated promising diagnostic capabilities in uveitis cases and ophthalmologist showed enthusiasm for the integration of AI into clinical practice.
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BACKGROUND/AIMS: Trachomatous trichiasis (TT) is a severe consequence of chronic inflammation/conjunctival scarring resulting from trachoma, the leading infectious cause of blindness worldwide. Our prospective cohort study evaluated the effectiveness of refresher training (RT) for experienced surgeons (1-22 years) on the outcomes of upper lid (UL) TT surgery in rural Ethiopia. METHODS: Patients undergoing UL TT surgery in at least one eye by a participating surgeon were included. Patients were split into two cohorts: patients enrolled prior to (C1) and after (C2) RT. RT consisted of a 1-week programme with practice on a HEAD START mannequin and supportive supervision in live surgery by expert trainers. Data were collected at preoperative enrolment, and at 6-month and 12-month follow-up visits. The primary outcome was development of postoperative TT (PTT). A series of multivariate generalised estimating equations were fit to model PTT involving potential covariates of interest. RESULTS: A total of 261 eyes contributed by 173 patients were studied between 2017 and 2019. By 1-year postoperatively, 37/128 eyes (28.9%) in C1 and 22/133 eyes (16.5%) in C2 had developed PTT (p=0.03). Other than surgeon RT participation, no factors studied were associated with differences in PTT. CONCLUSION: Our results indicate a significant reduction in the risk of PTT after experienced surgeons' participation in RT as compared with eyes receiving surgery before RT. This observation suggests a significant potential benefit of the RT with HEAD START mannequin practice and supportive supervision during surgery, and suggests RT may be a valuable strategy to improve surgical outcomes.
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INTRODUCTION: Accurate diagnosis and timely management are vital for favorable uveitis outcomes. Artificial Intelligence (AI) holds promise in medical decision-making, particularly in ophthalmology. Yet, the diagnostic precision and management advice from AI-based uveitis chatbots lack assessment. METHODS: We appraised diagnostic accuracy and management suggestions of an AI-based chatbot, ChatGPT, versus five uveitis-trained ophthalmologists, using 25 standard cases aligned with new Uveitis Nomenclature guidelines. Participants predicted likely diagnoses, two differentials, and next management steps. Comparative success rates were computed. RESULTS: Ophthalmologists excelled (60-92%) in likely diagnosis, exceeding AI (60%). Considering fully and partially accurate diagnoses, ophthalmologists achieved 76-100% success; AI attained 72%. Despite an 8% AI improvement, its overall performance lagged. Ophthalmologists and AI agreed on diagnosis in 48% cases, with 91.6% exhibiting concurrence in management plans. CONCLUSIONS: The study underscores AI chatbots' potential in uveitis diagnosis and management, indicating their value in reducing diagnostic errors. Further research is essential to enhance AI chatbot precision in diagnosis and recommendations.
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PURPOSE: As a potentially sight-threatening disease with ocular, systemic, and treatment-related complications, uveitis diminishes quality of life (QOL) and affects psychosocial well-being. This review summarizes the existing tools for evaluating psychosocial well-being and/or QOL in patients with uveitis, explores the biological and non-biological factors affecting psychosocial well-being and/or QOL, and proposes future directions for incorporating these tools into clinical practice. METHODS: A systematic search of the MEDLINE, Embase, and Cochrane databases from inception to June 8, 2022 was conducted, screening for articles focused on psychosocial well-being and/or QOL in patients with uveitis. Both quantitative and qualitative analyses were performed. RESULTS: In uveitis research, the most frequently studied patient-reported outcome measures were vision-related QOL (e.g. Visual Function Questionnaire [VFQ-25]) and health-related QOL (e.g. Short Form Survey [SF-36]), followed by mental health indicators including depression and anxiety. Instruments have also been developed specific to the pediatric population (e.g. Effects of Youngsters' Eyesight on Quality of Life [EYE-Q]). Generally, studies report worse psychosocial outcomes and QOL in patients with uveitis compared to the general population. Contributory factors include both clinical (e.g. visual impairment, ocular comorbidities) and patient-related (e.g. older age, female sex) factors. CONCLUSION: Given the heterogeneity of instruments used, it is worth considering standardization across large uveitis studies and trials. Beyond research, given the biopsychosocial effects on patients with uveitis, there are benefits to incorporating QOL and psychosocial assessments into clinical practice. Simplification of questionnaires into abridged forms, focusing on the most clinically relevant aspects of patient care, may be considered.
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PURPOSE: To determine the incidence of all-cause and cancer mortality (CM) in association with immunosuppression. DESIGN: Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and CM for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression. PARTICIPANTS: Patients with noninfectious OID, excluding those with human immunodeficiency infection or preexisting cancer. METHODS: Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this noninterventional cohort study. MAIN OUTCOME MEASURES: Overall mortality and CM. RESULTS: Over 187 151 person-years (median follow-up 10.0 years), during which 15 938 patients were at risk for mortality, we observed 1970 deaths, 435 due to cancer. Both patients unexposed to immunosuppressants (standardized mortality ratio [SMR] = 0.95, 95% confidence interval [CI], 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SIDs) (SMR = 1.04, 95% CI, 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents with patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio [aHR] = 0.88, 0.89, 0.90, 1.11) and CM (aHR = 1.25, 0.89, 0.86, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3-, or 5-year lags and across quartiles of immunosuppressant dose and duration. CONCLUSIONS: Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil, and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and CM over a median cohort follow-up of 10.0 years. These results suggest the safety of these agents with respect to overall and CM for patients treated with immunosuppression for a wide range of inflammatory diseases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Azatioprina , Neoplasias , Humanos , Estudios Retrospectivos , Metotrexato , Adalimumab , Inhibidores de la Calcineurina , Infliximab , Ácido Micofenólico/uso terapéutico , Estudios de Cohortes , Inhibidores del Factor de Necrosis Tumoral , Terapia de Inmunosupresión , Inmunosupresores/efectos adversos , Ciclosporina/uso terapéutico , Antimetabolitos , Alquilantes , Neoplasias/tratamiento farmacológicoRESUMEN
PURPOSE: To estimate the incidence/risk factors for cataract in noninfectious anterior uveitis. DESIGN: Retrospective multicenter cohort study (6 US tertiary uveitis sites, 1978-2010). METHODS: Data were harvested by trained expert reviewers, using protocol-driven review of experts' charts. We studied cataract incidence-newly reduced visual acuity worse than 20/40 attributed to cataract; or incident cataract surgery-in 3923 eyes of 2567 patients with anterior uveitis. RESULTS: Cataract developed in 507 eyes (54/1000 eye-years, 95% CI 49-59). Time-updated risk factors associated with cataract included older age (≥65 vs <18 years: adjusted hazard ratio [aHR] 5.04, 95% CI 3.04-8.33), higher anterior chamber cell grade (P(trend)=0.001), prior incisional glaucoma surgery (aHR 1.86, 95% CI 1.10-3.14), band keratopathy (aHR 2.23, 95% CI 1.47-3.37), posterior synechiae (aHR 3.71, 95% CI 2.83-4.87), and elevated intraocular pressure ≥30 vs 6-20 mm Hg (aHR 2.57, 95% CI 1.38-4.77). Primary acute (aHR 0.59, 95% CI 0.30-1.15) and recurrent acute (aHR 0.74, 95% CI 0.55-0.98) had lower cataract risk than chronic anterior uveitis. Higher-dose prednisolone acetate 1%-equivalent use (≥2 drops/day) was associated with >2-fold higher cataract risk in eyes with anterior chamber cell grades 0.5+ or lower but was not associated with higher cataract risk in the presence of anterior chamber cells of grade 1+ or higher. CONCLUSIONS: Cataract complicates anterior uveitis in â¼5.4/100 eye-years. Several fixed and modifiable risk factors were identified, yielding a point system to guide cataract risk minimization. Topical corticosteroids only were associated with increased cataract risk when anterior chamber cells were absent or minimally present, suggesting their use to treat active inflammation (which itself is cataractogenic) does not cause a net increase in cataract incidence.
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Catarata , Uveítis Anterior , Uveítis , Humanos , Estudios de Cohortes , Incidencia , Estudios Retrospectivos , Uveítis Anterior/complicaciones , Uveítis Anterior/epidemiología , Uveítis Anterior/tratamiento farmacológico , Factores de Riesgo , Uveítis/tratamiento farmacológico , Catarata/complicaciones , Enfermedad AgudaRESUMEN
PURPOSE: To evaluate the rate of, risk factors for, and outcomes of cataract surgery in patients with intermediate, posterior, and panuveitides treated with systemic corticosteroids and immunosuppression. DESIGN: Cohort study of participants from a randomized clinical trial. METHODS: A multicenter clinical trial with extended follow-up comprised the study setting. From the cohort of participants assigned to systemic therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study, 125 phakic eyes of 74 patients with intermediate, posterior, or panuveitides treated with systemic therapy were included. The main outcome measures were cataract surgery and visual acuity after cataract surgery. RESULTS: The cumulative incidence of cataract surgery was 43% at 7 years of follow-up, and the risk did not plateau. Risk factors for cataract surgery included age >50 years (hazard ratio [HR] 2.86, 95% CI 1.52, 5.42; P = .001), topical corticosteroid use (time-updated HR 3.13, 95% CI 1.42, 6.94; P = .005), glaucoma medication use (HR 2.75, 95% CI 1.38, 5.47; P = .004), and possibly history of anterior chamber inflammation (HR 1.90, 95% CI 0.95, 3.84; P = .07). Median gain in acuity and median best corrected visual acuity 1 year after cataract surgery were 4.8 lines and 20/25, respectively, among 42 eyes undergoing cataract surgery with 1-year follow-up data. CONCLUSIONS: Among patients with intermediate, posterior, and panuveitides, treated with oral corticosteroids and immunosuppression, there is a substantial long-term risk of cataract surgery. Visual acuity outcomes after cataract surgery are generally good.
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Catarata , Panuveítis , Uveítis , Humanos , Persona de Mediana Edad , Estudios de Seguimiento , Estudios de Cohortes , Uveítis/complicaciones , Uveítis/tratamiento farmacológico , Panuveítis/complicaciones , Catarata/complicaciones , Factores de Riesgo , Esteroides/uso terapéuticoRESUMEN
PURPOSE: To evaluate the effectiveness of 3 different intravitreal treatments for persistent or recurrent uveitic macular edema (ME): dexamethasone implant, methotrexate, and ranibizumab. DESIGN: Single-masked, randomized controlled clinical trial. PARTICIPANTS: Patients with minimally active or inactive uveitis and persistent or recurrent uveitic ME in one or both eyes. METHODS: Patients at 33 centers were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME received the same treatment in both eyes. MAIN OUTCOME MEASURES: The primary outcome, measured at 12 weeks, was reduction in central subfield thickness (CST) expressed as a proportion of baseline (CST per CST at baseline) assessed with spectral-domain OCT by readers masked to treatment assignment. Secondary outcomes included improvement and resolution of ME, change in best-corrected visual acuity (BCVA), and elevations in intraocular pressure (IOP). RESULTS: One hundred ninety-four participants (225 eligible eyes) were randomized to dexamethasone (n = 65 participants and 77 eyes), methotrexate (n = 65 participants and 79 eyes), or ranibizumab (n = 64 participants and 69 eyes). All received at least 1 injection of the assigned treatment. At the 12-week primary outcome point, each group showed significant reductions in CST relative to baseline: 35%, 11%, and 22% for dexamethasone, methotrexate, and ranibizumab, respectively. Reduction of ME was significantly greater in the dexamethasone group than for either methotrexate (P < 0.01) or ranibizumab (P = 0.018). Only the dexamethasone group showed a statistically significant improvement in BCVA during follow-up (4.86 letters; P < 0.001). Elevations of IOP by 10 mmHg, to 24 mmHg or more, or both were more common in the dexamethasone group; IOP spikes to 30 mmHg or more were uncommon overall and were not significantly different among groups. Reductions in BCVA of 15 letters or more were more common in the methotrexate group and typically were attributable to persistent ME. CONCLUSIONS: At 12 weeks, in eyes with minimally active or inactive uveitis, dexamethasone was significantly better at treating persistent or recurrent ME than methotrexate or ranibizumab. Risk of IOP elevation was greater with dexamethasone, but elevations to levels of 30 mmHg or more were infrequent. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.