Optical coherence tomography features in vitreoretinal lymphoma compared with non-infectious uveitis.

BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides. METHODS: Retrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022. The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included. RESULTS: There were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis. CONCLUSION: OCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.

Optic Disc Edema Is an Under-Recognized Feature of Birdshot Chorioretinitis.

BACKGROUND: Optic disc edema is a feature of many ophthalmic and neurologic conditions. It remains an underappreciated feature of birdshot chorioretinitis (BSCR), leading to delay in diagnosis and treatment. The purpose of our study was to identify clinical features that are concomitant with optic disc edema and suggest a diagnosis of BSCR. METHODS: Retrospective multicenter case series of 29 patients who were referred to a neuro-ophthalmologist or uveitis specialist for evaluation of disc edema and were ultimately diagnosed with BSCR. RESULTS: Fifty-four eyes of 30 patients, from the practices of 15 uveitis specialists, met the eligibility criteria. In addition to disc edema, concomitant features in all patients included vitritis, chorioretinal lesions, and retinal vasculitis. Visual recovery to 20/40 or better occurred in 26 of 29 patients. Visual acuity remained 20/100 or worse in 2 patients previously diagnosed with idiopathic intracranial hypertension, 1 patient previously diagnosed with optic neuritis, and 1 patient for whom treatment was delayed for years, leading to optic disc atrophy. CONCLUSIONS: Optic disc edema is a presenting feature in some cases of BSCR. A diagnosis of BSCR should be considered when disc edema occurs with vitritis, chorioretinal inflammation, and retinal vasculitis. Patients should be referred to a uveitis specialist for treatment.

Risk of hydroxychloroquine retinopathy in the community.

OBJECTIVES: We aimed to estimate the risk of HCQ retinopathy and its risk factors among incident users in the community. METHODS: Using the Rochester Epidemiology Project, a record-linkage system, a cohort of incident users of HCQ was identified from 27 counties in the American upper Midwest. HCQ retinopathy was defined based on characteristic paracentral automated 10-2 visual field (10-2 AVF) defects and parafoveal retinal photoreceptor layer changes on spectral domain optical coherence tomography. Cumulative incidence rates were estimated adjusting for competing risk of death. Risk factors for HCQ retinopathy were examined using Cox models. RESULTS: The study included 634 incident HCQ users (mean age at initial HCQ use was 53.7 years, 79% females, 91% white). Most common indications for HCQ were RA (57%) and SLE (19%). The average follow-up length was 7.6 years. Eleven patients developed HCQ retinopathy (91% females, 91% white). The majority used HCQ for RA (91%). The cumulative incidence rate at year 5 was 0%, which increased to 3.9% (95% CI 2.0, 7.4) by 10 years. Taking an HCQ dose ≥5 mg/kg was associated with a hazard ratio (HR) of 3.59 (95% CI 1.09, 11.84) compared with lower doses. There was a 48% increase [HR 1.48 (95% CI 1.03, 2.14)] in the risk of HCQ retinopathy for each 100 g of HCQ cumulative dose. CONCLUSION: The risk of HCQ retinopathy at 10 years of use is lower compared with previous prevalence-based estimations. A dose ≥5 mg/kg was associated with higher HCQ retinopathy risk.

EFFECT OF PHYSICIAN FACE MASK USE ON POSTINJECTION ENDOPHTHALMITIS.

PURPOSE: To examine the impact of physician face mask use on the rates and outcomes of postinjection endophthalmitis. METHODS: A multicenter retrospective, comparative cohort study comparing endophthalmitis rate and visual acuity of eyes that developed endophthalmitis after antivascular endothelial growth factor injections at Mayo Clinic Rochester (MCR) and at Mayo Clinic Health System sites depending on physician masking. RESULTS: A total of 164,824 injections were performed at MCR and Mayo Clinic Health System sites. Of these, 66,098 injections were in the no mask group and 98,726 injections were in the mask group. Overall, there were no differences in the rates of infectious endophthalmitis in the no mask versus mask cohorts (overall: no mask: 20 cases [0.0303%] vs. mask: 41 cases (0.0415%); P = 0.24; infectious: no mask: 12 cases [0.018%] versus mask: 13 cases [0.0132%]; P = 0.42). At MCR alone, there was a significant reduction in infectious endophthalmitis between the no mask versus mask groups (no mask: 9 cases [0.0297%] versus mask: 2 cases [0.003%]; P < 0.001). Only 2 cases of infectious endophthalmitis occurred at MCR after the face mask policy was implemented (1 in 30,000 injections). At presentation and at 6 months, the average visual acuity was similar for patients who developed endophthalmitis between the no mask versus mask groups. CONCLUSION: Physician face mask use did not affect the rate or outcome of postinjection endophthalmitis. However, there was a significant reduction at MCR after masking along with other quality improvement measures, including performance of injections in a dedicated procedure room and preparation of patients by nurses, that led to a low rate of endophthalmitis.

Clinical characteristics of inflammatory ocular disease in anti-neutrophil cytoplasmic antibody associated vasculitis: a retrospective cohort study.

Objective: To characterize the clinical correlates and outcome of inflammatory ocular disease (IOD) among patients with ANCA-associated vasculitides (AAV). Methods: Medical records of potential cases of AAV seen at Mayo Clinic from 2003 to 2013, inclusive, were reviewed to identify confirmed cases meeting the diagnosis of AAV using the Chapel Hill Consensus Conference 2012 descriptors. Records of confirmed cases of AAV were then further reviewed for IOD, and clinical characteristics, treatment and outcomes abstracted. Results: A total of 1171 confirmed cases of AAV were identified of which 183 patients (mean age 49.0 years; 51% female; 95% Caucasian) had IOD. The most common manifestation of IOD was injection of the eye (57%) followed by eye pain (46%) and visual acuity loss (18%). Scleritis was the most common type of IOD (22%) followed by episcleritis (21%), orbital inflammation (18%), lacrimal duct stenosis (10%) and uveitis (9%). Oral glucocorticoids were used to treat IOD in the majority of patients (96%). CYC and rituximab were the most frequently used immunosuppressive agents (54 and 36%, respectively). Of those with orbital inflammation, 52% underwent therapeutic surgical intervention. Clinical remission of IOD was achieved in 91% of patients but relapses were seen in 23%. Significant visual acuity loss was observed in only six patients. Conclusion: IOD is a common manifestation of AAV and seen in about 16% of patients with AAV. Scleritis, episcleritis and orbital inflammation are the most common subtypes. Most patients respond well to glucocorticoids and immunosuppression, but relapse of IOD is common.

The eye and tick-borne disease in the United States.

PURPOSE OF REVIEW: Tick-borne diseases are increasing in incidence and geographic distribution. Several diseases endemic to the United States have ophthalmic manifestations, including the most common tick-borne disease, Lyme borreliosis. As ocular complaints may lead a patient to seek medical evaluation, it is important to be aware of the systemic and ophthalmic manifestations of tick-borne diseases in order to make the correct diagnosis. RECENT FINDINGS: Vision-threatening ophthalmic manifestations are relatively common in Lyme disease and Rocky Mountain spotted fever. Ocular involvement is rare in babesiosis, tick-borne relapsing fever, Powassan encephalitis, ehrlichiosis, anaplasmosis, and Colorado tick fever.There are clear guidelines for diagnosis and treatment of Lyme disease; however, confusion and misinformation among the general public as well as controversy about chronic or late-stage Lyme disease can impact the evaluation of ophthalmic disease. Furthermore, there are many gaps in our knowledge regarding the pathophysiology of ocular borreliosis although it seems likely that Lyme uveitis is rare in the United States. SUMMARY: Knowledge of systemic and ophthalmic manifestations combined with an understanding of the epidemiology of disease vectors is crucial for the diagnosis of tick-borne diseases.

Appropriateness of Ophthalmology Recommendations From an Online Chat-Based Artificial Intelligence Model.

Objective: To determine the appropriateness of ophthalmology recommendations from an online chat-based artificial intelligence model to ophthalmology questions. Patients and Methods: Cross-sectional qualitative study from April 1, 2023, to April 30, 2023. A total of 192 questions were generated spanning all ophthalmic subspecialties. Each question was posed to a large language model (LLM) 3 times. The responses were graded by appropriate subspecialists as appropriate, inappropriate, or unreliable in 2 grading contexts. The first grading context was if the information was presented on a patient information site. The second was an LLM-generated draft response to patient queries sent by the electronic medical record (EMR). Appropriate was defined as accurate and specific enough to serve as a surrogate for physician-approved information. Main outcome measure was percentage of appropriate responses per subspecialty. Results: For patient information site-related questions, the LLM provided an overall average of 79% appropriate responses. Variable rates of average appropriateness were observed across ophthalmic subspecialties for patient information site information ranging from 56% to 100%: cataract or refractive (92%), cornea (56%), glaucoma (72%), neuro-ophthalmology (67%), oculoplastic or orbital surgery (80%), ocular oncology (100%), pediatrics (89%), vitreoretinal diseases (86%), and uveitis (65%). For draft responses to patient questions via EMR, the LLM provided an overall average of 74% appropriate responses and varied by subspecialty: cataract or refractive (85%), cornea (54%), glaucoma (77%), neuro-ophthalmology (63%), oculoplastic or orbital surgery (62%), ocular oncology (90%), pediatrics (94%), vitreoretinal diseases (88%), and uveitis (55%). Stratifying grades across health information categories (disease and condition, risk and prevention, surgery-related, and treatment and management) showed notable but insignificant variations, with disease and condition often rated highest (72% and 69%) for appropriateness and surgery-related (55% and 51%) lowest, in both contexts. Conclusion: This LLM reported mostly appropriate responses across multiple ophthalmology subspecialties in the context of both patient information sites and EMR-related responses to patient questions. Current LLM offerings require optimization and improvement before widespread clinical use.

Factors Influencing Instructors' Adoption and Continued Use of Computing Science Technologies: A Case Study in the Context of Cell Collective.

Acquiring computational modeling and simulation skills has become ever more critical for students in life sciences courses at the secondary and tertiary levels. Many modeling and simulation tools have been created to help instructors nurture those skills in their classrooms. Understanding the factors that may motivate instructors to use such tools is crucial to improve students' learning, especially for having authentic modeling and simulation learning experiences. This study designed and tested a decomposed technology acceptance model in which the perceived usefulness and perceived ease of use constructs are split between the teaching and learning sides of the technology to examine their relative weight in a single model. Using data from instructors using the Cell Collective modeling and simulation software, this study found that the relationship between perceived usefulness-teaching and attitude toward behavior was insignificant. Similarly, all relationships between perceived ease of use-teaching and the other variables (i.e., perceived usefulness-teaching and attitude toward behavior) became insignificant. In contrast, we found the relationships between perceived ease of use-learning and the other variables (i.e., perceived usefulness-teaching, perceived usefulness-learning, and attitude toward behavior) significant. These results suggest that priority should be given to the development of features improving learning over features facilitating teaching.

Epidemiology of Uveitis in Olmsted County, Minnesota: A Population-Based Follow-Up Study.

PURPOSE: To update the incidence of uveitis in a Midwestern U.S. county population. METHODS: Retrospective population-based cohort study. All Olmsted County, Minnesota residents diagnosed with uveitis from January 1, 2006 to December 31, 2015 were identified via the Rochester Epidemiology Project. Diagnoses were confirmed by a uveitis specialist. RESULTS: There were 371 incident uveitis cases, yielding an overall age- and sex-adjusted incidence rate of 26.9 per 100,000 per year (95% CI: 24.1-29.7). Females accounted for 202 (54.4%) cases, 306 (82.5%) were White, and 299 (80.6%) were anterior uveitis. Highest incidence was observed in patients ≥65 years old. No difference in incidence existed between sexes (p = .17). Incidence rates increased with age for uveitis overall (all anatomic subtypes) (p < .001), anterior uveitis (p < .001), and posterior uveitis (p < .001). Idiopathic uveitis accounted for 168 (45.3%) cases, more frequently diagnosed in females (50.0%) than males (39.6%) (p = .05). CONCLUSION: Uveitis incidence increased 1.6-fold over a 50-year span in this predominately White U.S. Midwestern county population.

Intraocular sarcoid-like reaction in patients with chronic lymphocytic leukemia.

OBJECTIVE: To investigate the frequency and clinical features of intraocular paraneoplastic sarcoid-like reaction (SLR) in patients with chronic lymphocytic leukemia (CLL). METHODS: Retrospective review of patients with CLL from January 1, 1980, to December 31, 2020. Eye examinations were searched for 22 keywords suggestive of SLR, and charts were manually reviewed. RESULTS: Of 4209 unique patients with CLL, 1021 (24%) had at least 1 eye examination on record, and 324 (8%) had 1 or more keyword eye examination findings. After manual review, 12 patients (<1%) were identified as having probable SLR with characteristic features (n = 7), possible but not classic (n = 1), or suspect but less likely (n = 4). All patients (n = 8) with probable or possible SLR were White, and half (n = 4) were male. Intraocular SLR was diagnosed a mean of 49.7 months after the CLL diagnosis (n = 7) or preceded the CLL diagnosis by 1 month (n = 1). Involvement was bilateral in 5 patients, with 13 total affected eyes and mean presenting Snellen visual acuity of 20/50. Common characteristic features on initial examination included vitreous cell (n = 13), anterior-chamber cell (n = 10), keratic precipitates (n = 9), posterior synechiae (n = 6), chorioretinal lesions (n = 5), and vitreous haze (n = 5). Treatment included topical corticosteroids alone (n = 5), with sub-Tenon corticosteroids (n = 1), or with steroid-sparing immunosuppressive agents (n = 1) or oral corticosteroids alone (n = 1). After a mean follow-up of 19.8 months, final mean visual acuity was 20/30. CONCLUSION: Intraocular SLRs affect fewer than 1% of patients with CLL. SLR should be on the differential diagnosis list for any CLL patient with ocular complaints, and most patients can be managed successfully with corticosteroids.

Ocular Whipple Disease: Cases Diagnosed Over Four Decades.

PURPOSE: To describe ocular involvement in subjects with Whipple's disease (WD). METHODS: Retrospective review of documented WD cases seen at Mayo Clinic between 1980 and 2021 with ocular involvement. RESULTS: Of 217 patients with WD, 30 had eye exams and four (two female, median age 58.5 years) had ocular involvement. Findings included anterior/intermediate uveitis (n = 2), intermediate uveitis and phlebitis (n = 1), and chorioretinitis with vitritis (n = 1). The diagnosis was confirmed by vitreous biopsy in three of four cases. In two cases, WD diagnosis was unconfirmed prior to the ocular diagnosis. Systemic manifestations included gastrointestinal symptoms in all patients, synovitis (n = 3), weight loss (n = 2), and pericarditis (n = 1). Mean time from onset of ocular symptoms to ocular diagnosis was 11 months (range 2-28 months). Prior systemic symptoms were present as long as 3 years. CONCLUSIONS: WD is uncommon and ocular involvement is even more rare. However, WD should be considered in the differential for all patients with chronic recalcitrant uveitis, especially in the setting of polyarthralgias and/or gastrointestinal symptoms. Vitreous biopsy is a reliable method to diagnose ocular WD.Abbreviations and Acronyms: Whipple's disease (WD), intestinal lipodystrophy (IL), polymerase-chain reaction (PCR), periodic acid-Schiff (PAS), trimethoprim/sulfamethoxazole (TMP/SMX).

VITREORETINAL INVOLVEMENT BY INDOLENT T-CELL LYMPHOPROLIFERATIVE DISORDER OF THE GASTROINTESTINAL TRACT DIAGNOSED BY FLUORESCENCE IN SITU HYBRIDIZATION.

PURPOSE: The purpose of this study was to describe an exceedingly rare presentation of secondary vitreoretinal involvement by the uncommon entity "indolent T-cell lymphoproliferative disorder of the gastrointestinal tract" and illustrate the utility of fluorescence in situ hybridization for diagnosis. METHODS: This is a case report. RESULTS: A 57-year-old woman with presumed iritis on chronic topical prednisolone acetate presented with increased vitreous opacities in the right eye. She had a history of biopsy-confirmed indolent T-cell lymphoproliferative disorder of the gastrointestinal tract involving the stomach and duodenum, JAK2 -rearrangement positive, controlled on maintenance oral methotrexate. Vitreous biopsy was unremarkable with small CD3-positive and CD4-positive and CD20-negative lymphocytes, along with histiocytes and fibroblasts. Immunostains showed CD4 positivity, and fluorescence in situ hybridization revealed a JAK2 gene rearrangement, consistent with the patient's previously diagnosed indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Intravitreal methotrexate injections were started in the right eye. MRI of the brain and lumbar puncture with cytology, MYD88 , IL10, and flow cytometry performed at the time of right eye vitreoretinal lymphoma diagnosis revealed no evidence of central nervous system lymphoma, but subsequent bone marrow biopsy demonstrated 5% involvement by indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, JAK2 -rearrangement positive, with a lung nodule on PET computed tomography. She returned 4 months later with fatigue, night sweats, and blurry vision in the left eye with vitreous and anterior chamber cellular infiltration and retinal vasculitis. CONCLUSION: T-cell vitreoretinal lymphoma is rare, and diagnosis can be challenging. Despite inconclusive cytology in this case, interphase fluorescence in situ hybridization detected a JAK2 gene rearrangement, which confirmed the involvement by indolent T-cell lymphoproliferative disorder of the gastrointestinal tract and prompted appropriate treatment and workup for recurrent systemic or central nervous system lymphoma.

Ophthalmic adverse effects of BRAF inhibitors.

To determine the frequency, characteristics, and clinical course of ophthalmic side effects associated with systemic BRAF inhibitor therapy. Medical records of patients taking BRAF inhibitors for the treatment of systemic malignances at Mayo Clinic, Rochester from 01/01/2010 to 08/30/2021, were retrospectively reviewed. Of 901 patients, 14 (1.6%) patients experienced an ophthalmic side effect. Mean age at presentation of the side effect was 60 years (median 59, range 50-80) and 11 (79%) were male. The most common side effect was uveitis in 7 (50%) patients, followed by dry eye in 4 (29%) patients, and central serous chorioretinopathy in 2 (14%) patients, with singular cases of cranial nerve VI palsy and conjunctival edema. A comparison between individual BRAF inhibitors (vemurafenib vs. dabrafenib vs. encorafenib) revealed that patients taking encorafenib had a shorter interval to any ophthalmic adverse event (mean 55.6 vs. 9.8 vs. 4.0 months, p = 0.03) and were the only patients to experience documented dry eye syndrome (DES) in this series. Outcomes were known in 13 (93%) patients, and ophthalmic adverse effects resolved or were controlled without discontinuing therapy in 10 (77%). Uveitis was successfully treated with topical corticosteroids in 4 patients, while 3 patients with refractory uveitis (2 with panuveitis and 1 with unspecified uveitis) required discontinuation of BRAF inhibitor therapy. Ophthalmic adverse events related to systemic BRAF inhibitor use are rare, with estimated frequency of 1.6%. Most events can be treated with local ophthalmic therapy. BRAF inhibitors provide life-saving therapy, and their discontinuation should be avoided.

Epidemiology and Clinical Characteristics of Presumed Ocular Histoplasmosis in Olmsted County, Minnesota.

PURPOSE: To describe the incidence, prevalence, and clinical characteristics of presumed ocular histoplasmosis syndrome (POHS) in a Histoplasma endemic region. METHODS: The International Classification of Diseases, 9th and 10th Revision codes were used to search the Rochester Epidemiology Project, a record-linkage system for medical care provided in Olmsted County, MN. Medical records were reviewed to confirm POHS diagnoses in county residents from January 1, 2006, to December 31, 2015. Age- and sex-adjusted incidence rates were calculated and adjusted to the 2010 U.S. White population. RESULTS: There were 18 incident cases (30 eyes) and 87 prevalent cases (131 eyes). The incidence rate was 1.35 per 100,000 per year. The mid-study prevalence rate was 0.064%. Choroidal neovascularization (CNV) occurred in 17.4% of the affected eyes. At the last follow-up, 16.8% of the affected eyes had POHS-related decreased visual acuity (<20/40). CONCLUSION: This study assesses the epidemiology and clinical features of POHS in a Midwestern U.S. county. ABBREVIATIONS/ACRONYMS: POHS = Presumed ocular histoplasmosis syndrome; ICD = International Classification of Diseases; CI = Confidence interval; VA = Visual acuity; Anti-VEGF = Anti-vascular endothelial growth factor; REP = Rochester Epidemiology Project, CNV = Choroidal neovascularization.

Outcomes of Patients With Active Diabetic Macular Edema at the Time of Cataract Surgery Managed With Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To investigate the outcomes of cataract surgery in patients with active diabetic macular edema (DME) who are receiving active treatment with intravitreal anti-vascular endothelial growth factor (VEGF) injections in the perioperative period. DESIGN: Retrospective clinical cohort study. METHODS: We reviewed all patients who underwent cataract surgery and were receiving intravitreal anti-VEGF injections from January 1, 2012 through December 31, 2017. Thirty-seven eyes underwent cataract surgery and received ≥1 intravitreal anti-VEGF injection for a diagnosis of DME within 6 months before surgery. Outcome measures included the development of subretinal or intraretinal fluid in the 6 months after surgery, timing of injections, number of injections, best-corrected visual acuity, and central subfield thickness. RESULTS: There was a significant improvement between pre- and postoperative best-corrected visual acuity when comparing all eyes (Ps < .0001) and no significant difference in central subfield thickness before and after surgery (P > .05). There were 30 eyes (81.1%) that had fluid on the preoperative optical coherence tomography scan. Seventeen eyes (45.9%) developed new or worsening postoperative DME. Comparing the eyes that did or did not develop worsening DME, there were no differences in postoperative visual acuities (P > .05). Eyes that did develop new fluid had significant increases in postoperative central subfield thickness at both 1 month (350 vs 320 µm, P = .036) and 6 months (342 vs 305 µm, P = .013). CONCLUSION: In a real-world setting, patients with cataracts and actively treated DME may undergo cataract surgery but may see a worsening of DME not immediately affecting the best-corrected visual acuity.

Clinical Utility of Antiretinal Antibody Testing.

IMPORTANCE: The clinical utility of most antiretinal antibodies (retina antibodies) currently available for testing remains unclear and unproven. Despite this, the presence of retinal antibodies is included in current diagnostic autoimmune retinopathy criteria. OBJECTIVE: To evaluate the clinical significance of comprehensive retinal antibody evaluations currently offered in North America. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, 14 patients without autoimmune retinopathy were recruited into the Mayo Clinic Neuroimmunology Biorepository for this study between January 1, 2019, and October 1, 2019. These serum samples without autoimmune retinopathy were sent in masked fashion to a Clinical Laboratory Improvement Amendments-certified laboratory. Using similar methods, the Mayo Clinic Neuroimmunology Research Laboratory independently assessed the same sample to ascertain reproducibility of the findings. MAIN OUTCOMES AND MEASURES: Results of the autoimmune retinopathy and cancer-associated retinopathy panels. RESULTS: Thirteen of 14 (93%; 95% CI, 66%-100%) serum samples tested positive for retinal antibodies, with a median of 5 retinal antibodies (range, 0-8) per patient at the Clinical Laboratory Improvement Amendments-certified laboratory, which provides a specificity of 7% (95% CI, 0%-34%). Confirmatory immunohistochemistry staining in human retina was present in 12 of 14 samples (86%). α-Enolase was found in 9 (64%). The only retinal antibody not present was recoverin. These nonspecific retinal antibody results were replicated at the Mayo Clinic Laboratory on Western blot using pig retina proteins as substrate. CONCLUSIONS AND RELEVANCE: The presence of retinal antibodies in 93% of the patients without autoimmune retinopathy indicates a lack of specificity and that most detectable retinal antibodies have limited clinical relevance in the evaluation of patients for suspected autoimmune retinopathy. Current retinal antibody testing, other than recoverin, should be interpreted with caution, especially for cases of low clinical suspicion. The poor specificity is important to recognize to prevent the potentially unnecessary commencement of systemic immunosuppressants that may result in significant extraocular adverse effects. Identification of biomarkers that have a high predictive value for inflammatory or autoimmune retinal diseases is needed to move the field forward.

Birdshot chorioretinopathy presenting in a teenager.

PURPOSE: To describe clinical features of the youngest patient with well-documented HLA-A29-positive birdshot chorioretinopathy (BCR). OBSERVATIONS: A 17-year-old female presented with poor night vision and floaters. Examination revealed bilateral vitritis, retinal vasculitis, and numerous cream-colored ovoid lesions in the fundus. Fluorescein angiography revealed bilateral optic disc leakage, large vessel leakage and diffuse capillary ferning. There were hundreds of small hypocyanescent spots evenly distributed in the posterior pole of both eyes on indocyanine green angiography. Workup was positive for HLA-A29.2. Systemic immunosuppression with adalimumab 40mg/0.4mL was initiated every two weeks and escalated to weekly dosing. The patient's early age of disease onset prompted evaluation of her parents. The mother's exam was normal and she was HLA-A29 negative. Examination of the father revealed peripapillary choroidal lesions as well as hypocyanescent spots on ICG. HLA-typing revealed the presence of HLA-A29.2. CONCLUSIONS AND IMPORTANCE: BCR rarely occurs in the pediatric population. We present the youngest patient with well-documented BCR in the literature to highlight that this disease deserves consideration even in young patients. Interestingly, choroidal lesions were also found in an asymptomatic parent with HLA-A29.2 positivity.

Epidemiology and Clinical Characteristics of Episcleritis and Scleritis in Olmsted County, Minnesota.

PURPOSE: To determine the population-based incidence and disease associations of episcleritis and scleritis in a midwestern U.S. DESIGN: Population-based retrospective cohort study. METHODS: All residents of Olmsted County, Minnesota from 2006 to 2015 were identified by using the Rochester Epidemiology Project. A total of 223 episcleritis cases and 77 scleritis cases were identified. The incidence and disease associations of episcleritis and scleritis were assessed, as well as scleritis recurrence rates, treatment, and complications. RESULTS: Incidence rates for episcleritis and scleritis were 15.39 and 5.54 per 100,000 per year, respectively. Females accounted for 60.1% of episcleritis and 51.9% of scleritis cases. The mean age at diagnosis was 40.2 years of age for episcleritis and 48.8 years of age for scleritis. In the episcleritis cases, the incidence in females was higher (P = .01). There were no significant differences between sexes for scleritis incidence (P = .75); 23.4% of scleritis patients had an associated systemic disease. Patients with systemic disease showed a trend toward an increased risk of recurrence, but it was not statistically significant. There was a slightly decreased risk of scleritis recurrence with older age at diagnosis (hazard ratio [HR]: 0.73; P = .058; 95% confidence interval [CI]: 0.52-1.01). At last follow-up, most eyes with scleritis (90.4%) had good visual acuity (better than 20/40), and 92.3% had stable or improved visual acuity. CONCLUSIONS: The Olmsted County, Minnesota population had a lower incidence of episcleritis and a higher incidence of scleritis than populations in previous studies. The population-based results from the current study may provide information that is more applicable to a primary eye care setting.

Regional variations in chronic rhinosinusitis, 2003-2006.

OBJECTIVES: 1. Characterize patient visits for chronic rhinosinusitis on the basis of age, gender, race, diagnostic services, and medication use. 2. Evaluate regional differences in patient visits for chronic rhinosinusitis. STUDY DESIGN: Analysis of cross-sectional survey data from two national databases of ambulatory medical encounters. SETTING: Not applicable. SUBJECTS AND METHODS: Four years (2003-2006) of data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey were analyzed. Visits involving chronic rhinosinusitis were identified by using reported diagnostic codes from the International Classification of Diseases, Ninth Revision. They were weighted to provide national estimates of care. Data were analyzed with the Pearson chi(2) test using the SPSS 16.2 Complex Samples Module, taking into account the complex survey design and multiple time periods. RESULTS: A total of 4617 patient visits for chronic rhinosinusitis were identified, accounting for 1.95 percent of all visits. With the application of weights to this sample, these visits represent 91.2 million national visits. A significantly higher proportion of visits in the South involved African Americans (Pearson chi(2) = 69.5, F = 6.7, df = 2.8, 2118, P < 0.01). Significantly fewer diagnostic services were provided or ordered in the Northeast (Pearson chi(2) = 64.8, F = 4.0, df = 4.3, 3247, P < 0.01). Providers in the Northeast were also significantly less likely to order or renew more than three medications at the visit (Pearson chi(2) = 54.0, F = 3.1, df = 2.6, 1930, P < 0.05). No regional differences were seen for age, gender, or setting type. CONCLUSION: Significant regional variations exist for chronic rhinosinusitis in patient demographics, diagnosis, and management. Continuing research is needed to refine physician awareness, evaluation, and treatment of this disorder.

Histoplasmosis Following Systemic Immunomodulatory Therapy for Ocular Inflammation.

PURPOSE: Histoplasmosis is a known complication of systemic immunosuppressive therapy, particularly among patients who are receiving tumor necrosis factor α inhibitors. There are limited data on the development of disseminated or pulmonary histoplasmosis among patients who are receiving systemic immunosuppressive medication for noninfectious ocular inflammation. DESIGN: Retrospective case series. METHODS: We reviewed all patients with uveitis or scleritis who subsequently developed pulmonary or disseminated histoplasmosis at the Mayo Clinic in Rochester, Minnesota between September 1, 1994 and July 1, 2017, with a 3:1 age- and sex-matched control cohort who did not develop histoplasmosis. This was a single institutional study examining patients that developed histoplasmosis after the initiation of systemic immunomodulatory therapy (IMT). Patients had to develop either disseminated or pulmonary histoplasmosis while receiving systemic immunosuppressive therapy and have an ophthalmic examination at Mayo Clinic Rochester. The control group was comprised of patients who received systemic IMT for ocular inflammation but did not develop histoplasmosis. RESULTS: Nine cases of histoplasmosis were identified: 2 disseminated and 7 pulmonary. Both patients with disseminated histoplasmosis were taking tumor necrosis factor α inhibitors. Seven of the 9 patients received systemic antifungal medication, including both disseminated cases. Over a median follow-up of 4.4 years, none of the patients died, and there were no recurrences of histoplasmosis. When compared to the control cohort, there was no correlation between length of time on IMT and the risk of histoplasmosis. CONCLUSIONS: Ocular inflammation patients on systemic immunomodulatory therapy may develop pulmonary or disseminated histoplasmosis. Most cases require treatment with systemic antifungal medication, but it might not be necessary to stop systemic immunomodulatory medication for ocular inflammation. Ophthalmologists should be aware that patients receiving systemic immunomodulatory therapy have a higher risk of developing Histoplasma infections. Prompt diagnosis and treatment using the expertise of an infectious diseases specialist may ensure low mortality for these patients.