Systemic prime exacerbates the ocular immune response to heat-killed Mycobacterium tuberculosis.

Post-infectious uveitis describes the condition of chronic immune mediated ocular inflammation associated with pathogens such as Mycobacterium tuberculosis (Mtb). Mtb associated post-infectious uveitis can be modeled in mice by intravitreal injection of heat-killed Mtb (HKMtb). To better understand how prior systemic exposure to the pathogen alters the local immune response to Mtb, we used flow cytometry and multiplex ELISAs to compare ocular responses to intravitreal HKMtb in the presence or absence of a systemic "prime" of HKMtb. Priming resulted in exacerbation of local inflammation with significantly increased clinical and histologic inflammation scores and increased vitreous cytokines concentrations one day after intravitreal injection of HKMtb. Seven days after injection, uveitis in unprimed animals had largely resolved. In contrast in primed animals, clinical signs of chronic inflammation were associated with a significant increase in the number of ocular T cells, NK cells, and Ly6Chi macrophages and increasing vitreous concentrations of IL-17, VEGF, MIG(CXCL9), IP-10(CXCL10), IL-12p40 and MIP-1α(CCL3). In mice lacking mature T and B cells (RAG2 deficient), the impact of priming on the ocular immune response was ameliorated with significantly lower vitreous cytokine concentrations and spontaneous resolution of uveitis. Altogether these results suggest that the ocular response to Mtb is exacerbated by prior systemic Mtb infection and chronic post-infectious uveitis is mediated by local production of cytokines and chemokines that amplify Th17 and Th1 responses. This mouse model of chronic Mtb associated uveitis will help elucidate mechanisms of disease in patients with post-infectious uveitis.

RESPONSE OF INFLAMMATORY CYSTOID MACULAR EDEMA TO TREATMENT USING ORAL ACETAZOLAMIDE.

PURPOSE: To determine the treatment effect of oral acetazolamide on refractory inflammatory macular edema. METHODS: A retrospective review of identified patients with uveitic or pseudophakic macular edema treated using acetazolamide between 2007 and 2014. Visual acuity and central macular subfield thickness was determined at baseline and at first follow-up. Baseline optical coherence tomography features were analyzed as predictors of acetazolamide response. RESULTS: Sixteen patients (19 eyes) of 61 screened met all criteria. Mean age was 57.9 years (19.7-81.1). The most common diagnosis was idiopathic uveitis (n = 6, 31.6%). Mean uveitis duration was 4.4 years (0.2-27.5). Average central macular subfield thickness decreased significantly (from 471.8 ± 110.6 µm to 358.3 ± 50.4 µm) (P < 0.0001). Average visual acuity (logarithm of the minimum angle of resolution) improved significantly from 20/54 (0.43 ± 0.25) to 20/37 (0.27 ± 0.16) (P = 0.003). Pretreatment optical coherence tomographies demonstrated intraretinal fluid (n = 19, 100%), subretinal fluid (n = 8, 42.1%), epiretinal membrane (n = 13, 68.3%), and vitreomacular traction (n = 1, 5.2%). No optical coherence tomography characteristic was predictive of a response to therapy. CONCLUSION: There is a significant benefit to vision and central macular subfield thickness after acetazolamide treatment in patients with inflammatory macular edema. In patients with refractory inflammatory macular edema, treatment using acetazolamide can provide anatomical and visual benefit without corticosteroid-related adverse effects.

Targeting Interleukin-23 in the Treatment of Noninfectious Uveitis.

The interleukin (IL)-23/IL-17 axis plays a central role in the pathogenesis of immune-mediated diseases such as psoriasis, psoriatic arthritis, Crohn's disease, and uveitis. Therefore, targeting the IL-23/IL-17 axis has become the focus of multiple clinical trials for drug development in patients with autoimmune diseases. We briefly describe the biology of the IL-23/IL-17 axis and its relevance to the pathogenesis of experimental and clinical uveitis, and review the monoclonal antibody therapies targeting this pathway. Finally, 2 ongoing phase 2 trials of the anti-IL-23 biologic therapy ustekinumab (STELARA, Janssen Biotech Inc, Horsham, PA) in patients with noninfectious uveitis are introduced.

Cytokines in uveitis.

PURPOSE OF REVIEW: Increasing evidence supports Th17 cells as key mediators of ocular inflammatory disease. Cytokines that are important for the development and pathologic function of these cells are potential therapeutic targets in patients with immune mediated uveitis. This review provides an overview of these cytokines including recent insights about their roles in ocular inflammation from laboratory and clinical studies. RECENT FINDINGS: Interleukin (IL)-6, IL-10, IL-17, IL-22, IL-23 and tumour necrosis factor-alpha (TNFα) are cytokines that have been examined for their functional role in uveitis and their relationship to pathologic Th17 cells. Studies in animal models, particularly in experimental autoimmune uveitis (EAU), have been instrumental in studying the role of these cytokines in disease pathogenesis. More recently, studies on aqueous, vitreous and serum from patients with uveitis using flow cytometry and multiplex ELISA bead-based methodologies have provided insights into the contribution of Th17 cells and the related cytokines in ocular inflammatory diseases. The central role of IL-23 in determining the pathologic Th17 fate has made it an effective therapeutic target in systemic diseases such as psoriasis and thereby an attractive potential target for patients with immune-mediated uveitis. SUMMARY: Th17 cells, and their related cytokines, are important inflammatory mediators in autoimmune uveitis. Animal and human studies continue to provide new information to direct development of new cytokine-targeted therapies for patients with uveitis.

Tubulointerstitial nephritis and uveitis.

PURPOSE OF REVIEW: Tubulointerstitial nephritis and uveitis (TINU) is an important yet underrecognized ocular inflammatory syndrome. This review summarizes key historical publications that identified and defined the syndrome, and more recent literature that reveal the importance of urinary ß2-microglobulin testing and kidney biopsy in the diagnostic evaluation of patients with TINU. Additionally, research studies providing new insights into disease pathogenesis are highlighted. RECENT FINDINGS: In contrast with initial reports of TINU manifesting exclusively as an anterior uveitis in pediatric patients, more recent reports have identified TINU in patients of all ages with a wide range of ocular manifestations. Urinary ß2-microglobulin has emerged as a sensitive and specific laboratory screening test, and the role of kidney biopsy in differentiating TINU from sarcoidosis continues to evolve. Genetic studies have identified HLA-DQA101, HLA-DQB105, and HLA-DRB101 as high-risk alleles and the identification of antimonomeric C-reactive protein antibodies suggests a role for humoral immunity in disease pathogenesis. Management strategies have evolved to include systemic anti-inflammatory treatment as a result of important outcome studies in patients with significant renal and ocular disease. SUMMARY: With greater recognition, understanding, and treatment of this syndrome, both ocular inflammation and renal disease can be better addressed.

The enhancer of trithorax and polycomb gene Caf1/p55 is essential for cell survival and patterning in Drosophila development.

In vitro data suggest that the human RbAp46 and RbAp48 genes encode proteins involved in multiple chromatin remodeling complexes and are likely to play important roles in development and tumor suppression. However, to date, our understanding of the role of RbAp46/RbAp48 and its homologs in metazoan development and disease has been hampered by a lack of insect and mammalian mutant models, as well as redundancy due to multiple orthologs in most organisms studied. Here, we report the first mutations in the single Drosophila RbAp46/RbAp48 homolog Caf1, identified as strong suppressors of a senseless overexpression phenotype. Reduced levels of Caf1 expression result in flies with phenotypes reminiscent of Hox gene misregulation. Additionally, analysis of Caf1 mutant tissue suggests that Caf1 plays important roles in cell survival and segment identity, and loss of Caf1 is associated with a reduction in the Polycomb Repressive Complex 2 (PRC2)-specific histone methylation mark H3K27me3. Taken together, our results suggest suppression of senseless overexpression by mutations in Caf1 is mediated by participation of Caf1 in PRC2-mediated silencing. More importantly, our mutant phenotypes confirm that Caf1-mediated silencing is vital to Drosophila development. These studies underscore the importance of Caf1 and its mammalian homologs in development and disease.

Immunology of Retinitis Pigmentosa and Gene Therapy-Associated Uveitis.

The underlying immune state of inherited retinal degenerations (IRDs) and retinitis pigmentosa (RP) has been an emerging area of interest, wherein the consequences have never been greater given the widespread recognition of gene therapy-associated uveitis (GTU) in gene therapy clinical trials. Whereas some evidence suggests that the adaptive immune system may play a role, the majority of studies indicate that the innate immune system is likely the primary driver of neuroinflammation in RP. During retinal degeneration, discrete mechanisms activate resident microglia and promote infiltrating macrophages that can either be protective or detrimental to photoreceptor cell death. This persistent stimulation of innate immunity, overlaid by the introduction of viral antigens as part of gene therapy, has the potential to trigger a complex microglia/macrophage-driven proinflammatory state. A better understanding of the immune pathophysiology in IRD and GTU will be necessary to improve the success of developing novel treatments for IRDs.

Aqueous Macrophages Contribute to Conserved CCL2 and CXCL10 Gradients in Uveitis.

Purpose: Uveitis is a heterogenous group of inflammatory eye disease for which current cytokine-targeted immune therapies are effective for only a subset of patients. We hypothesized that despite pathophysiologic nuances that differentiate individual disease states, all forms of eye inflammation might share common mechanisms for immune cell recruitment. Identifying these mechanisms is critical for developing novel, broadly acting therapeutic strategies. Design: Experimental study. Subjects: Biospecimens from patients with active or inactive uveitis and healthy controls. Methods: Protein concentration and single cell gene expression were assessed in aqueous fluid biopsies and plasma samples from deidentified patients with uveitis or healthy controls. Main Outcome Measures: The concentration of 31 inflammatory proteins was measured in all aqueous samples, as well as plasma samples from patients with active uveitis. Chemokine and cytokine ligand and receptor expression were assessed in individual cell types from aqueous biopsies obtained from patients with active uveitis. Results: We identified 6 chemokines that were both elevated in active uveitis compared with controls and enriched in aqueous compared with plasma during active uveitis (C-C motif chemokine ligand [CCL]2, C-X-C motif chemokine ligand [CXCL]10, CXCL9, CXCL8, CCL3, and CCL14), forming potential gradients for migration of immune cells from the blood to the eye. Of these, CCL2 and CXCL10 were consistently enriched in the aqueous of all patients in our cohort, as well as in a larger cohort of patients from a previously published study. These data suggest that CCL2 and CXCL10 are key mediators in immune cell migration to the eye during uveitis. Next, single cell RNA sequencing suggested that macrophages contribute to aqueous enrichment of CCL2 and CXCL10 during human uveitis. Finally, using chemokine ligand and receptor expression mapping, we identified a broad signaling network for macrophage-derived CCL2 and CXCL10 in human uveitis. Conclusions: These data suggest that ocular macrophages may play a central role, via CCL2 and CXCL10 production, in recruiting inflammatory cells to the eye in patients with uveitis. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Systemic Administration of Acazicolcept, a Dual CD28 and Inducible T cell Costimulator Inhibitor, Ameliorates Experimental Autoimmune Uveitis.

Purpose: Combined inhibition of CD28 and inducible T cell costimulator (ICOS) pathways with acazicolcept (ALPN-101) represents a potential new treatment for uveitis. Here, we evaluate preclinical efficacy using experimental autoimmune uveitis (EAU) in Lewis rats. Methods: Efficacy was tested in 57 Lewis rats treated with either systemic (subcutaneous) or local (intravitreal) administration of acazicolcept and compared to treatment with a matched Fc-only control or corticosteroid. Impact of treatment on uveitis was assessed using clinical scoring, optical coherence tomography (OCT), and histology. Ocular effector T cell populations were determined using flow cytometry, and multiplex ELISA used to measure aqueous cytokine concentrations. Results: When compared to Fc control treatment, systemic acazicolcept led to statistically significant decreases in clinical score (P < 0.01), histologic score (P < 0.05), and number of ocular CD45+ cells (P < 0.01). Number of ocular CD4+ and CD8+ T cells expressing IL-17A+ and IFNγ+ were also decreased with statistical significance (P < 0.01). Similar results were achieved with corticosteroids. Intravitreal acazicolcept decreased inflammation scores when compared to untreated fellow eyes and to Fc control treated eyes, although not statistically significant. Systemic toxicity, measured by weight loss, occurred in the corticosteroid-treated, but not in the acazicolcept-treated animals. Conclusions: Systemic treatment with acazicolcept statistically significantly suppressed EAU. Acazicolcept was well-tolerated without the weight loss associated with corticosteroids. Acazicolcept may be an effective alternative to corticosteroids for use in treating autoimmune uveitis. Additional studies are needed to clarify the optimal dose and route for use in humans. Translational Relevance: We show that T cell costimulatory blockade could be an effective mechanism for treating uveitis.

Cataract Surgery in Patients With Uveitis Treated With Systemic Therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study: Risk Factors and Outcomes.

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.

Consensus-based recommendations for optical coherence tomography angiography reporting in uveitis.

BACKGROUND/AIMS: To establish a consensus in the nomenclature for reporting optical coherence tomography angiography (OCTA findings in uveitis. METHODS: The modified Delphi process consisted of two rounds of electronic questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-one items were included for discussion. The three main areas of discussion were: wide field OCTA (WF-OCTA), nomenclature of OCTA findings and OCTA signal attenuation assessment and measurement. Seventeen specialists in uveitis and retinal imaging were selected by the executive committee to constitute the OCTA nomenclature in Uveitis Delphi Study Group. The study endpoint was defined by the degree of consensus for each question: 'strong consensus' was defined as >90% agreement, 'consensus' as 85%-90% and 'near consensus' as >80% but <85%. RESULTS: There was a strong consensus to apply the term 'wide field' to OCTA images measuring over 70° of field of view, to use the terms 'flow deficit' and 'non-detectable flow signal' to describe abnormal OCTA flow signal secondary to slow flow and to vessels displacement respectively, to use the terms 'loose' and 'dense' to describe the appearance of inflammatory choroidal neovascularisation, and to use the percentage of flow signal decrease to measure OCTA ischaemia with a threshold greater than or equal to 30% as a 'large area'. CONCLUSIONS: This study sets up consensus recommendations for reporting OCTA findings in uveitis by an expert panel, which may prove suitable for use in routine clinical care and clinical trials.

Grading Anterior Chamber Inflammation with Anterior Segment Optical Coherence Tomography: An Overview.

The objective grading of anterior chamber inflammation (ACI) has remained a challenge in the field of uveitis. While the grading criteria produced by the Standardization of Uveitis Nomenclature (SUN) International Workshop have been widely adopted, limitations exist including interobserver variability and grading confined to discrete categories rather than a continuous measurement. Since the earliest iterations of optical coherence tomography (OCT), ACI has been assessed using anterior segment OCT and shown to correlate with slit-lamp findings. However, widespread use of this approach has not been adopted. Barriers to standardization include variability in OCT devices across clinical settings, lack of standardization of image acquisition protocols, varying quantification methods, and the difficulty of distinguishing inflammatory cells from other cell types. Modern OCT devices and techniques in artificial intelligence show promise in expanding the clinical applicability of anterior segment OCT for the grading of ACI.

IDIOPATHIC PENETRATION OF CILIA INTO THE POSTERIOR SEGMENT PRESENTING AS SECTORAL SCLERITIS WITH PROGRESSIVE INTRAOCULAR INFLAMMATION.

PURPOSE: To report two cases of idiopathic intraocular cilia presenting as sectoral scleritis with progressive intraocular inflammation. METHODS: Both patients were treated with intravitreal antibiotics and underwent pars plana vitrectomy where the cilia were removed and identified on histopathology. RESULTS: One patient developed a retinal detachment while being treated for presumed endophthalmitis. The intraocular cilium was discovered during pars plana vitrectomy. In the second case, the cilium was detected on dilated fundus exam and was believed to be the cause of the patient's scleritis and vitritis. Therapeutic vitrectomy was performed. In both cases, the cilia were positively identified on histopathology. CONCLUSION: Idiopathic intraocular penetration of cilia should be considered in the differential diagnosis of sectoral scleritis with progressive intraocular inflammation.

Characterization of Gene Therapy Associated Uveitis Following Intravitreal Adeno-Associated Virus Injection in Mice.

Purpose: To characterize the intraocular immune cell infiltrate induced by intravitreal adeno-associated virus (AAV) gene therapy. Methods: AAV vectors carrying plasmids expressing green fluorescent protein under the control of PR2.1 were injected intravitreally into AAV naive and AAV primed C57Bl/6 mice. Clinical inflammation was assessed using optical coherence tomography. Intraocular immune cell populations were identified and quantified by flow cytometry on days 1, 7, and 29 after intravitreal injection and compared with sham and fellow eye controls. Results: Optical coherence tomography inflammation score and total CD45+ cell number were significantly higher in AAV injected eyes compared to uninjected fellow eye and sham injected controls. Clinically apparent inflammation (vitritis on optical coherence tomography) and cellular inflammation (CD45+ cell number) was significantly increased in AAV injected eyes and peaked around day 7. Vitritis resolved by day 29, but cellular inflammation persisted through day 29. On day 1, neutrophils and activated monocytes were the dominant cell populations in all AAV injected eyes. On day 7, eyes of AAV exposed animals had significantly more dendritic cells and T cells than eyes of AAV naive animals. By day 29, CD8- T cells were the dominant CD45+ cell population in AAV injected eyes. Conclusions: Intravitreal AAV injection in mice generates clinically evident inflammation that is mild and seems to resolve spontaneously. However, the total number of intraocular CD45+ cells, particularly T cells, remain elevated. Both innate and adaptive immune cells respond to intravitreal AAV regardless of prior immune status, but the adaptive response is delayed in AAV naive eyes.

Swept source OCTA reveals a link between choriocapillaris blood flow and vision loss in a case of tubercular serpiginous-like choroiditis.

Optical coherence tomography angiography (OCTA) is a non-invasive technique that is useful in the diagnosis and management of patients with posterior uveitis. Here we report the use of swept source OCTA (SS-OCTA) in a patient with tuberculosis (TB) associated serpiginous like choroiditis (TB-SLC) that made a full visual recovery following treatment with ATT, local and systemic corticosteroids, and systemic immune modulation. By comparing en face images of choriocapillaris (CC) blood flow before and after treatment, we conclude that the patient's visual recovery was associated with resolution of extensive CC flow deficits. This case highlights the utility of SS-OCTA in the multimodal evaluation of patients with choroidal inflammation, and the potential for good visual recovery in patients treated for TB-SLC.

Primed Mycobacterial Uveitis (PMU) as a Model for Post-Infectious Uveitis.

The term 'uveitis' describes a heterogeneous set of conditions that all feature intraocular inflammation. Broadly, uveitis is defined by etiology: infection or autoimmunity. Infectious uveitis requires treatment with the appropriate antimicrobial agents, while autoimmune uveitis requires treatment with corticosteroids or other immunosuppressive agents. Post-infectious uveitis is a form of chronic uveitis that requires corticosteroids to control immune sequela following the initial infection. Uveitis associated with Mycobacterium tuberculosis (Mtb) infection is a well-recognized form of post-infectious uveitis, but the mechanisms of disease are not fully understood. To understand the role mycobacterial antigens and innate ligands play in stimulating chronic ocular inflammation following mTB infection, the model Primed Mycobacterial Uveitis (PMU) was developed for use in mice. This manuscript outlines the methods for generating PMU and monitoring the clinical course of inflammation using color fundus and optical coherence tomography (OCT) imaging. PMU is induced by immunization with heat-killed mycobacterial extract followed by intravitreal injection of the same extract into one eye seven days later. Ocular inflammation is monitored longitudinally using in vivo imaging and followed by sample collection for a wide range of assays, including histology, flow cytometry, cytokine analysis, qPCR, or mRNA sequencing. The mouse model of PMU is a useful new tool for studying the ocular responses to mTB, the mechanism of chronic uveitis, and for preclinical effectiveness tests of new anti-inflammatory therapies.

Automated Quantification of Choriocapillaris Lesion Area in Patients With Posterior Uveitis.

PURPOSE: To validate a custom algorithm for automated identification and quantification of clinically relevant inflammatory choriocapillaris (CC) lesions from en face swept-source optical coherence tomography (SS-OCTA) images. DESIGN: Observational case series. METHODS: Twenty eyes of 14 patients with posterior uveitis were imaged. The machine-generated en face OCTA CC slabs were exported to a computing platform, where a custom algorithm performed unsupervised lesion boundary delineation and area quantification. Lesions identified by the algorithm (AG) were compared to those identified by 2 masked human graders (HG1 and HG2), using the Sørensen-Dice coefficient (DSC) and intraclass correlation coefficient (ICC). Intragrader and intravisit reliability were determined by coefficient of variation (CV) and DSC. RESULTS: The AG demonstrated excellent agreement with both HGs in determination of lesion area (HG1 vs AG ICC 0.92, 95% CI 0.81-0.97, HG2 vs AG ICC 0.91, 95% CI 0.78-0.97). The AG demonstrated good spatial overlap (DSC ≥0.70) with both HGs in 14 of 20 (70%) eyes and at least 1 HG in 16 of 20 (80%) eyes. Poor spatial overlap (DSC between 0.31 and 0.69) was associated with the presence of a choroidal neovascular membrane and low-contrast lesion boundaries. Intravisit repeatability for the AG was superior to both HGs (CV 2.6% vs >5%). CONCLUSION: This custom algorithm demonstrated a high degree of agreement with HGs in identification of inflammatory CC lesions and outperformed HGs in reproducibility. Automated CC lesion delineation will support the development of objective and quantitative biomarker of disease activity in patients with posterior uveitis.

Assessing the Uniformity of Uveitis Clinical Concepts and Associated ICD-10 Codes Across Health Care Systems Sharing the Same Electronic Health Records System.

IMPORTANCE: Big data studies may allow for the aggregation of patients with rare diseases such as uveitis to answer important clinical questions. Standardization of uveitis-related variables will be necessary, including the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes used to identify patients of interest. There are currently limited data on the uniformity of diagnosis mapping to ICD-10 codes for uveitis diagnoses among different health systems. OBJECTIVE: To assess the degree of uniformity in mapping of uveitis clinical concepts to ICD-10 codes across health care systems using the same electronic health record (EHR) system. DESIGN, SETTING, AND PARTICIPANTS: This multicenter survey study was conducted between September 14 and October 9, 2020, at 5 academic health care systems that use the Epic EHR. Researchers from the University of Washington, Harvard University, Stanford University, Yale University, and the University of California, San Francisco queried 54 uveitis-related diagnostic terms and recorded the associated ICD-10 codes. MAIN OUTCOMES AND MEASURES: The degree of uniformity for uveitis clinical concepts and associated ICD-10 codes. RESULTS: Fifty-four uveitis-related diagnostic terms were queried within the Epic EHR at 5 different health care systems. There was perfect agreement among all 5 centers for 52 of the 54 diagnostic terms. Two diagnostic terms had differences in ICD-10 coding: juvenile idiopathic arthritis associated chronic uveitis and intermediate uveitis. Intermediate uveitis was associated with codes H20.1x (ICD-10 description: chronic iridocyclitis) or H20.9 (ICD-10 description: unspecified iridocyclitis) in 3 centers while being associated with code H30.2x (ICD-10 description: posterior cyclitis) at the 2 remaining centers. The discrepancies appear to be related to a recent update in diagnostic mapping in the Epic EHR. CONCLUSIONS AND RELEVANCE: This study suggests that ICD-10 code mapping to uveitis diagnostic terminology appears to be highly uniform at different centers with the Epic EHR. However, temporal changes in diagnosis mapping to ICD-10 codes and a lack of 1-to-1 mapping of diagnosis to ICD-10 code add additional sources of complexity to the interpretation of big data studies in uveitis.

Quantitative Analysis of the Choriocapillaris in Uveitis Using En Face Swept-Source Optical Coherence Tomography Angiography.

PURPOSE: To perform a quantitative analysis of choriocapillaris (CC) flow deficits (FDs) in patients with uveitis. DESIGN: Retrospective cross-sectional study. METHODS: Swept-source optical coherence tomography based angiography (SS-OCTA) macular volume scans (3 × 3 mm and 6 × 6 mm) were obtained using the Plex Elite 9000. En face CC images were generated and analyzed using an automated FD identification algorithm. Three quantitative metrics were determined for each eye: FD number (FDN), mean FD size (MFDS), and FD density (FDD). Quantitative metrics were compared between uveitis and control eyes. The uveitis cohort was further subdivided by the presence or absence of choroidal involvement, and quantitative metrics were compared between subgroups and normal control subjects. RESULTS: A total of 38 eyes from 38 control subjects and 73 eyes from 73 uveitis subjects were included in this study. Eyes with uveitis have significantly larger CC MFDS (3- × 3-mm scans; P < .0001; 6- × 6-mm scans; P < .0001) and higher FDD (P = .0002; P = .0076, respectively) compared to control eyes. Additional analysis determined that these differences were due to the choroidal disease subgroup, which demonstrates significantly larger MFDS (3 × 3 = 1,108 µm2; 6 × 6 = 1,104 µm2) compared to both normal control eyes (752 µm2; P < .0001; 802 µm2; P < .0001, respectively) and uveitis patients without choroidal involvement (785 µm2; P < .0001; 821 µm2; P < .0001, respectively). No significant differences were found between the quantitative metrics of control subjects and patients without choroidal involvement. CONCLUSIONS: Automated quantification of CC can identify pathological FDs and provide quantitative metrics describing such lesions in patients with uveitis. Posterior uveitis patients have significantly larger CC FDs than patients with other forms of uveitis.