ROLE OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN DETECTING AND MONITORING INFLAMMATORY CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To investigate the utility of optical coherence tomography angiography (OCTA) for the detection of inflammatory choroidal neovascularization (iCNV) and monitoring their response to treatment. METHODS: A retrospective review of patients with a diagnosis of uveitis and associated iCNV with active exudation was performed. Active iCNV was determined by spectral domain OCT and/or fluorescein angiogram. Spectral domain OCTA outer retina to choriocapillaris slabs was evaluated for the presence of iCNV. Follow-up OCTA images were qualitatively assessed to determine whether regression of iCNV occurred after treatment. RESULTS: Thirteen eyes of 12 patients were included. The etiologies of uveitis include punctate inner choroidopathy (n = 4), multifocal choroiditis (n = 2), presumed sarcoid uveitis (n = 2), tuberculous choroiditis (n = 1), birdshot chorioretinopathy (n = 1), syphilitic uveitis (n = 1), serpiginous choroiditis (n = 1), and idiopathic panuveitis (n = 1). Inflammatory choroidal neovascularization was detected on en face OCTA in 10 of 13 eyes (76.9%). After iCNV treatment, en face OCTA demonstrated complete regression of iCNV in 5 of 10 eyes (50%), partial regression in 2 of 10 eyes (20%), and no regression in 3 of 10 eyes (30%). CONCLUSIONS: Optical coherence tomography angiography is an effective modality for detecting iCNV and could provide detailed visualization regarding location, morphologic structure, and flow of the iCNV and its response to therapy.

Taking Control of Castleman Disease: Leveraging Precision Medicine Technologies to Accelerate Rare Disease Research.

Castleman disease (CD) is a rare and heterogeneous disorder characterized by lymphadenopathy that may occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric), the latter typically occurring secondary to excessive proinflammatory hypercytokinemia. While a cohort of multicentric Castleman disease (MCD) cases are caused by Human Herpes Virus-8 (HHV-8), the etiology of HHV-8 negative, idiopathic MCD (iMCD), remains unknown. Breakthroughs in "omics" technologies that have facilitated the development of precision medicine hold promise for elucidating disease pathogenesis and identifying novel therapies for iMCD. However, in order to leverage precision medicine approaches in rare diseases like CD, stakeholders need to overcome several challenges. To address these challenges, the Castleman Disease Collaborative Network (CDCN) was founded in 2012. In the past 3 years, the CDCN has worked to transform the understanding of the pathogenesis of CD, funded and initiated genomics and proteomics research, and united international experts in a collaborative effort to accelerate progress for CD patients. The CDCN's collaborative structure leverages the tools of precision medicine and serves as a model for both scientific discovery and advancing patient care.

Treatment Outcomes of Intravitreal Aflibercept for Uveitic Macular Edema.

BACKGROUND/AIMS: To evaluate the efficacy of intravitreal aflibercept for UME (uveitic macular). METHODS: A retrospective review of records of patients that received aflibercept for UME from January 2017 to August 2022 was conducted. The primary outcomes were mean change in visual acuity (VA) and central subfield thickness (CST) 6 and 12 months from the start of aflibercept treatment. RESULTS: A total of 16 eyes of 12 patients were included. Indications for treatment included eyes that had previously demonstrated a history of elevated intraocular pressure secondary to a steroid response (n = 10) or a history of non-response or partial response to local corticosteroids (n = 6). Fifteen eyes (94%) demonstrated a reduction in CST after their initial injection. At 6-months, mean VA gain was 2.6 ± 7.7 letters (p = 0.24) from a mean VA of 67.8 ± 10.7 letters at baseline and mean CST improved by 97.6 ± 113.5 µm (p = 0.004) from 458.6 ± 123.1 µm at baseline. Fourteen eyes had 12-months of follow up and received a median of 4 injections over 12 visits. The mean VA at 12-months remained stable compared to baseline (mean change of -1.4 ± 12.5 letters (p = 0.87)) while the CST improved by a mean of 90.9 ± 114.6 µm (p = 0.053) compared to baseline. CONCLUSION: Intravitreal aflibercept injections resulted in reduced central subfield thickness at all time-points. It appears to be an effective treatment alternative for UME, particularly for patients who are not responsive to local corticosteroids or who have contraindications to corticosteroid treatment.

Ultrawide-field fluorescein angiography features in patients with anterior uveitis.

PURPOSE: To evaluate the utility of ultrawide-field fluorescein angiography (UWFFA) in patients with anterior uveitis by investigating the detection of retinal vascular leakage (RVL) and the subsequent implications on disease diagnosis and management. STUDY DESIGN/MATERIALS AND METHODS: Patients, who were referred to the National Eye Institute (NEI) for evaluation of anterior uveitis and underwent UWFFA imaging at the initial visit, were included in this study. The electronic medical records of eligible patients were reviewed. The UWFFA images were assessed for severity of retinal vascular leakage, presence of macular leakage, and optic disc leakage by a two-grader system, and intergrader agreement was calculated using the κ-value. Patients with altered diagnoses and management attributable to UWFFA results were noted. RESULTS: A total of 93 eyes of 63 patients were included in the study. Of 93 eyes, 31 (33.3%) eyes had RVL on UWFFA, with 26 (28.0%) eyes and 5 (5.4%) eyes showing mild and moderate-severe RVL, respectively. Twenty-five (26.9%) eyes showed macular leakage, and 7 (7.5%) eyes showed optic disc leakage. The κ-values ranged from 0.85 - 0.87 indicating excellent intergrader agreement. Of the 31 eyes with RVL, the diagnosis was changed to anterior/intermediate uveitis for 9 (29.0%) eyes and to panuveitis for 4 (12.9%) eyes. Systemic treatment was escalated in 5 patients. CONCLUSION: Our results suggest that UWFFA imaging is useful in detecting subclinical posterior involvement in patients with anterior uveitis. Moreover, UWFFA results in altered diagnosis and treatment approaches in a portion of patients.

Extensive Subretinal Fibrosis Associated with Pseudoxanthoma Elasticum.

PURPOSE: To report an unusual case of pseudoxanthoma elasticum (PXE) presenting with an inflammatory phenotype associated with atypical and rapidly progressive subretinal fibrosis. METHODS: Observational case report. RESULTS: A patient with a history of pseudoxanthoma elasticum presented with rapidly progressive subretinal fibrosis, particularly in the left eye, over the course of one year. The patient was noted at presentation to have intraocular inflammation, outer retinal attenuation, multifocal choroiditis-like lesions, and intraretinal fluid (in the absence of obvious clinical or angiographic signs of exudative CNVM). An ocular inflammatory phenotype was diagnosed, and the patient was treated with a combination of local steroids and systemic corticosteroids/immunomodulatory agents. After initiation of these agents, there was demonstrated functional and structural improvement, with partial outer retinal reconstitution, decreased intraretinal fluid, and lack of further progression of subretinal fibrosis. CONCLUSION: This report describes an inflammatory phenotype of PXE associated with severe and atypical subretinal fibrosis. This case expands upon the currently known spectrum of inflammatory phenotypes associated with PXE. Treatment with corticosteroids or immunomodulatory treatment should be considered in similar cases.

Isolated Optic Disc Granuloma as a Presenting Sign of Sarcoidosis.

PURPOSE: To report a case of an optic disc granuloma secondary to sarcoidosis in the absence of any systemic symptoms nor evident signs of intraocular inflammation at the time of presentation. METHODS: Retrospective case report. RESULTS: A 59-year-old Caucasian woman with previously unrevealing systemic work up was referred to the uveitis service for persistent optic disc edema of the right eye for over 1 year. Fundoscopic examination revealed an optic disc granuloma with associated hyper-reflectivity on OCT and high surface reflectivity with medium internal reflectivity on B-scan ultrasound. CT chest was negative, however, a PET scan demonstrated extensive FDG activity in the mediastinum and bilateral hilum, consistent with a diagnosis of sarcoidosis. CONCLUSION: Optic nerve head granulomas can rarely present as the only clinical sign of sarcoidosis. In these cases, additional imaging modalities may be needed to make the appropriate diagnosis.

Changes in Choroidal Vascularity Index (CVI) in Intermediate Uveitis.

Purpose: To investigate the longitudinal changes in choroidal vascularity index (CVI) in eyes with active and quiescent intermediate uveitis using enhanced depth imaging optical coherence tomography (EDI-OCT). Methods: EDI-OCT images of eyes with active and quiescent intermediate uveitis were retrospectively reviewed and binarized using ImageJ software. Choroidal parameters including CVI, total choroidal area (TCA), luminal area (LA), stromal area (SA), and subfoveal choroidal thickness (SCT) were measured and compared between baseline and follow-up visits among eyes with active and quiescent intermediate uveitis. Results: Thirty-eight eyes from 21 patients with active intermediate uveitis and 30 eyes from 17 patients with quiescent intermediate uveitis were included. CVI in eyes with active intermediate uveitis significantly increased from baseline (66.50% ± 3.40%) with resolution of inflammation on follow-up (68.82% ± 3.90%; P < 0.001). In eyes with quiescent intermediate uveitis at baseline eyes, CVI did not significantly change after follow-up (66.34% ± 3.19% to 66.25% ± 3.13%; P = 0.850). Conclusions: CVI significantly increased when active inflammation in intermediate uveitis resolved while CVI remained unchanged at follow-up in quiescent intermediate uveitis. Translational Relevance: CVI may be a useful noninvasive tool to monitor treatment response in intermediate uveitis. Our findings also highlight the involvement of choroidal vasculature in uveitic eyes without any clinical evidence of choroiditis.

Non-physician grader reliability in measuring morphological features of the optic nerve head in stereo digital images.

OBJECTIVE: To introduce a new method of grading optic nerve stereo disc photographs and evaluate reproducibility of assessments by non-physician graders in a reading center. METHODS: Three non-physician graders, experienced in grading features of the retina but not the optic nerve head (ONH), were trained by glaucoma specialists to assess digital stereo color images of the ONH. These graders assessed a total of 2554 digital stereo disc images from glaucoma cases and controls participating in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study by outlining the optic cup and disc. Inter-grader reproducibility of area, height, and width measurements was analyzed. RESULTS: Among all images, the intraclass correlation (95% confidence interval) was 0.90 (0.89, 0.90) for the cup area using only color cues; 0.92 (0.91, 0.92) for the cup area using contour and vascular cues; and 0.99 (0.99, 0.99) for the optic disc area. The intraclass correlation for cup-to-disc ratio (CDR) was 0.61 (0.58, 0.63), as determined by the ratio of optic cup area to optic disc area (using contour and vascular cues). The CDR difference by graders for area was ≤ 0.1 in 65% of images using color/vascular cues and ≤0.1 in 71% of images using color cues. CONCLUSIONS: After adequate training, non-physician graders were able to measure the optic nerve CDR with high inter-grader reliability.

Using a Mystery-Caller Approach to Examine Access to Prostate Cancer Care in Philadelphia.

PURPOSE: Prior work suggests that access to health care may influence the diagnosis and treatment of prostate cancer. Mystery-caller methods have been used previously to measure access to care for health services such as primary care, where patients' self-initiate requests for care. We used a mystery-caller survey for specialized prostate cancer care to assess dimensions of access to prostate cancer care. MATERIALS AND METHODS: We created an inventory of urology and radiation oncology practices in southeastern Pennsylvania. Using a 'mystery caller' approach, a research assistant posing as a medical office scheduler in a primary care office, attempted to make a new patient appointment on behalf of a referred patient. Linear regression was used to determine the association between time to next available appointment with practice and census tract characteristics. RESULTS: We successfully obtained information on new patient appointments from 198 practices out of the 223 in the region (88.8%). Radiation oncology practices were more likely to accept Medicaid compared to urology practices (91.3% vs 36.4%) and had shorter mean wait times for new patient appointments (9.0 vs 12.8 days). We did not observe significant differences in wait times according to census tract characteristics including neighborhood socioeconomic status and the proportion of male African American residents. CONCLUSIONS: Mystery-caller methods that reflect real-world referral processes from primary care offices can be used to measure access to specialized cancer care. We observed significant differences in wait times and insurance acceptance between radiation oncology and urology practices.