Peripheral ulcerative keratitis associated with tralokinumab therapy: a case report and review of IL-13 inhibitor-associated ocular surface disease.

BACKGROUND: Dupilumab and tralokinumab are interleukin-binding monoclonal antibodies used to treat systemic atopic disease. Use of these medications in management of atopic dermatitis (AD) is known to cause conjunctivitis. Dupilumab therapy has also been associated with more severe ocular surface disease, which has not previously been described in association with tralokinumab. This report describes a case of tralokinumab-associated conjunctivitis and peripheral ulcerative keratitis and reviews the spectrum and proposed mechanisms of ocular surface disease triggered by these medications. CASE PRESENTATION: A 61-year-old male with no rheumatologic or ocular history presented with bilateral papillary conjunctivitis and right eye peripheral ulcerative keratitis (PUK). PUK was arrested using oral corticosteroids and doxycycline, and long-term control of papillary conjunctivitis was achieved using topical tacrolimus ointment, allowing continuation of effective AD management with tralokinumab. CONCLUSION: This case report documents ulcerative keratitis occurring in association with tralokinumab therapy for AD, which has previously been described with dupilumab but not tralokinumab. This report demonstrates the need for vigilant ocular surface monitoring for patients on tralokinumab and illustrates successful management and long-term control of adverse ocular events associated with this medication.

A Case of Rhegmatogenous Retinal Detachment in Chronic Myeloid Leukemia.

PURPOSE: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by uncontrolled proliferation of granulocytes, caused the BCR-ABL1 fusion gene. While ocular manifestations of CML are rare, the presentations can range from asymptomatic to sudden vision loss. CML associated ocular findings that have been reported include retinal hemorrhages, leukemic infiltrates, and optic disc edema, but a rhegmatogenous retinal detachment (RRD) in the setting of CML has not been described. METHODS: Case report. RESULTS: A 21-year-old man presented with intermittent vision loss in his right eye, tinnitus in the right ear, and abdominal distension. Work up revealed significant leukocytosis, splenomegaly, and a positive BCR-ABL1 mutation. He was diagnosed with CML and started on systemic therapy. Exam of the right eye revealed a large intraocular mass. After two weeks of systemic treatment, the large elevation in the right eye had improved, allowing visualization of diffuse subretinal whitening. At follow up, an RRD secondary to an atrophic hole in an area of prior subretinal infiltrates were noted. He underwent repair with a scleral buckle. Postoperative course was complicated by redetachment with proliferative vitreoretinopathy, which led to an unrepairable detachment, despite multiple surgeries with silicone oil tamponade. CONCLUSIONS: Ocular findings related to CML are rare, with the lowest incidence when compared to other leukemias, and are associated with worse outcomes. Posterior segment findings include intraretinal hemorrhages, Roth spots, and retinal infiltrates. This unique case describes an RRD in CML retinopathy with an aggressive course and poor anatomical result.

Ocular Findings Aid in Diagnosis of West Nile Virus.

INTRODUCTION: West Nile virus disease, which is endemic to the United States, is a rarely reported systemic infection that can be difficult to diagnose. Chorioretinitis is an uncommon manifestation of West Nile virus but has pathognomonic ocular findings that can aid in diagnosis. CASE PRESENTATION: A 66-year-old man presented with acute onset fever, chills, and dyspnea. He underwent an extensive but nondiagnostic workup during hospitalization. New visual complaints prompted ophthalmology consultation. Funduscopic examination showed macular hemorrhages and midperipheral chorioretinal lesions. Fluorescein angiography revealed target-like lesions in a radial distribution, which is pathognomonic for West Nile virus chorioretinitis. Serology confirmed the diagnosis of West Nile virus disease. Systemic and ocular symptoms improved with supportive care. DISCUSSION: West Nile virus disease has many nonspecific manifestations. History of recent mosquito exposure is not always readily elicited. In patients with visual symptoms, eye examination can help in its diagnosis. CONCLUSIONS: West Nile virus should be considered in patients with acute febrile or neurological illness during mosquito season.

Ocular Emergencies During the Coronavirus Disease 'Safer at Home Order' in Wisconsin.

INTRODUCTION: The coronavirus pandemic created large shifts in utilization of hospital resources, patient presentations, and delivery of medical care. OBJECTIVES: This retrospective study evaluated the ocular emergencies at a tertiary-care academic hospital in Wisconsin during the COVID-19-related "Safer at Home" order. METHODS: Ophthalmology consultations performed March 23 through May 26, 2020, were compared to the same time period in the 4 preceding years and the subsequent year. Billing codes were obtained to evaluate the diagnoses and procedures performed during this time frame. RESULTS: In 2020, 155 consultations were performed (42 emergency department, 113 inpatient), compared to a mean of 214 over the 5 other study years. The incidence rate ratio (IRR) of total consultations in 2020 was 0.72 (P ≤ 0.001) compared to previous years. Significantly fewer emergency department consultations were performed (IRR 0.62, P ≤ 0.001), while inpatient consultations were similar (IRR 0.88, P = 0.119). The most common diagnosis across all study years was fracture of the skull/orbit with injury to the eye/orbit. In 2020, 13% of consultations led to a procedure, compared to a total of 16% in the other years (IRR 0.59, P = 0.018). CONCLUSIONS: This study demonstrated a 28% reduction in ophthalmology consultations at a major university hospital in Wisconsin during the COVID-19-related "Safer at Home" order, though the number of consultations leading to surgery were stable. This suggests that while patients with less acute needs may have deferred care, those requiring urgent surgery still presented to the emergency department. These data may help hospitals appropriately allocate eye care resources during future public health emergencies.

Contrast Sensitivity Testing in Age-Related Macular Degeneration Using Motion Diamond Stimulus.

PURPOSE: This study was performed to characterize changes in contrast sensitivity (CS) that occur in patients with age-related macular degeneration (AMD) using a novel test, the motion diamond stimulus (MDS). METHODS: This was a cross-sectional study in which 20 subjects with unilateral exudative AMD (eAMD) and contralateral dry AMD received 3 assessments: the Pelli-Robson (PR) CS Chart, the MDS test, and a visual function questionnaire-25 (VFQ-25). CS results from the PR, and MDS tests were compared across 3 groups: eyes with eAMD vs dry AMD, eAMD vs control, dry AMD vs control. Healthy, undilated eyes from another study served as the control group. Significance was determined using ANOVA analysis for the MDS output parameters (α: overall contrast threshold, ß: adaptability of the visual system) and PR logCS. Patients were also administered the VFQ-25 to assess vision-related quality of life. RESULTS: The ANOVA of the MDS data demonstrated a significant difference in visual function according to the ß parameter of the 3 groups, but no significant difference in the α parameter. PR CS results for the 3 groups were significantly different, further supporting the MDS results. Post-hoc analysis showed a significant difference in ß and PR log CS between the eAMD and control eyes. CONCLUSION: The MDS test is valuable in discerning CS impairments in patients with AMD. It can provide further insight into the visual changes experienced by patients with AMD and has potential to quantify visual function changes that are not found on visual acuity testing alone.

MACULAR HOLE FORMATION ASSOCIATED WITH INTENSE PULSED LIGHT THERAPY.

PURPOSE: To describe the first case of macular hole formation following intense pulsed light therapy. METHODS: This is a retrospective case report. A 68-year-old woman presented with blurry vision that occurred 1 day following intense pulsed light therapy for hair removal. RESULTS: A full thickness macular hole, which had not been previously documented was noted on fundus exam. Ocular coherence tomography confirmed a full-thickness macular hole. DISCUSSION: Laser treatment for hair removal has been reported to cause ocular injuries including iris atrophy, pupillary distortion, cataracts, and uveitis. Intense pulsed light therapy, a specific type of laser therapy, has been reported to cause iris transillumination defects, anterior uveitis, and pupil abnormalities. Our case is the first to describe a macular hole secondary to intense pulsed light therapy. The etiology of the macular hole is postulated to be secondary to possible thermal injury with absorption of energy at the level of the retinal pigment epithelium. This emphasizes the role and importance of preventative measures, such as protective glasses in reducing the risk of ocular injuries.

Development and Validation of a Natural Language Processing Algorithm to Extract Descriptors of Microbial Keratitis From the Electronic Health Record.

PURPOSE: The purpose of this article was to develop and validate a natural language processing (NLP) algorithm to extract qualitative descriptors of microbial keratitis (MK) from electronic health records. METHODS: In this retrospective cohort study, patients with MK diagnoses from 2 academic centers were identified using electronic health records. An NLP algorithm was created to extract MK centrality, depth, and thinning. A random sample of patient with MK encounters were used to train the algorithm (400 encounters of 100 patients) and compared with expert chart review. The algorithm was evaluated in internal (n = 100) and external validation data sets (n = 59) in comparison with masked chart review. Outcomes were sensitivity and specificity of the NLP algorithm to extract qualitative MK features as compared with masked chart review performed by an ophthalmologist. RESULTS: Across data sets, gold-standard chart review found centrality was documented in 64.0% to 79.3% of charts, depth in 15.0% to 20.3%, and thinning in 25.4% to 31.3%. Compared with chart review, the NLP algorithm had a sensitivity of 80.3%, 50.0%, and 66.7% for identifying central MK, 85.4%, 66.7%, and 100% for deep MK, and 100.0%, 95.2%, and 100% for thin MK, in the training, internal, and external validation samples, respectively. Specificity was 41.1%, 38.6%, and 46.2% for centrality, 100%, 83.3%, and 71.4% for depth, and 93.3%, 100%, and was not applicable (n = 0) to the external data for thinning, in the samples, respectively. CONCLUSIONS: MK features are not documented consistently showing a lack of standardization in recording MK examination elements. NLP shows promise but will be limited if the available clinical data are missing from the chart.

Maculopathy Secondary to Pentosan Polysulfate Use: A Single-Center Experience.

AIM: To investigate the prevalence of retinal pathology in patients with a history of exposure to pentosan polysulfate sodium (PPS). METHODS: Patients exposed to PPS and seen in the ophthalmology clinic at Northwestern University during 1/1/2002 to 1/1/2019 were identified from electronic health records (EHR) by an electronic data warehouse (EDW) search. Visual acuity (VA), reasons for clinic visit, ocular conditions, and duration of exposure to PPS were noted. Chart review was performed for fundus exam findings and ophthalmologic imaging, specifically fundus photography, fundus autofluorescence, and ocular coherence tomography (OCT) images. When OCT or fundus photography was available, studies were evaluated by two independent graders. RESULTS: A total of 131 patients who were exposed to PPS and seen at the Northwestern Ophthalmology clinic were identified in the EHR. Forty patients of 131 had imaging. Patients with imaging or fundus examination suspicious for PPS maculopathy were placed into the suspect group. Of the 40 patients that had imaging, 5 (12.5%) had features suspicious for PPS maculopathy. Of the remaining 91, 5 (5.4%) had macular pigmentary changes described on fundus exam. Among the 10 patients in the suspect group, the average duration of PPS use was 4.2 years (range 0.3-11.6 years, interquartile range 5.5 years) and the average cumulative dose was 380g (range 29-1092g, interquartile range 132g). CONCLUSION: A novel drug-induced maculopathy has been associated with PPS use with a distinct clinical constellation that can be accurately identified with multimodal imaging.

Procedures, Visits, and Procedure Costs in the Management of Microbial Keratitis.

PURPOSE: To investigate the burden of procedures, visits, and procedure costs in the management of microbial keratitis (MK). METHODS: Medical records of patients from an academic hospital outpatient facility between December 2013 and May 2018 were retrospectively reviewed. Patients were included if they were older than the age of 18 years, recruited for study of likely MK, and not concurrently undergoing treatment for other acute eye conditions. For procedural costs, Medicare data for billing were obtained using the Center for Medicare and Medicaid Services Physician Fee Lookup tool. RESULTS: A total of 68 patients were included for analysis. Patients were on average 51.3 years (SD = 19.5), 55.9% women (n = 38), and 89.7% White (n = 61). Per person, the average number of procedures was 2.9 (SD = 4.2). The average number of visits was 13.9 (SD = 9.2) over an average of 26.9 weeks (SD = 24.3). Age (P < 0.0001), positive Gram stain (P = 0.03), and mixed Gram stain (P = 0.002) were positively associated with the number of procedures. Age (P = 0.0003), fungal keratitis (P = 0.02), and mixed Gram stain (P = 0.01) were positively associated with the number of visits. Race was inversely associated with the number of procedures (P = 0.045) and visits (0.03). Patients with bacterial keratitis were more likely to have amniotic membrane grafts (P = 0.01) and tarsorrhaphies (P = 0.03) than fungal patients. Across all procedures performed for the management of MK, the mean cost per patient was $1788.7 (SD = $3324.62). CONCLUSIONS: Patients incur many procedural costs and attend many visits during the management of MK. These findings emphasize the importance of patient-provider communication for frequent follow-up care and the potential need to perform procedures for disease management.

Contrast Sensitivity Testing in Retinal Vein Occlusion Using a Novel Stimulus.

Purpose: This study evaluated a novel tool known as the motion diamond stimulus (MDS), which utilizes contrast-generated illusory motion in dynamic test regions to determine contrast sensitivity (CS). Methods: Patients with treated unilateral retinal vein occlusions (RVOs) underwent three assessments: the MDS, the Pelli-Robson (PR), and the National Eye Institute's Visual Function Questionnaire (VFQ-25). The MDS assessment produced two data end points, α and ß. The α value represents the overall contrast threshold level and the ß value serves to quantify the adaptability of the visual contrast system. The CS parameters from the MDS and log CS PR output values were used to compare RVO eyes (n = 20) to control eyes (n = 20). Results: The study participants had a mean composite VFQ-25 score of 89.5 ± 10.4 on the VFQ-25. A significant difference was observed between the RVO eyes and the control eyes in PR log CS scores (P value = 0.0001) and in MDS α value (P value = 0.01). No difference in MDS ß value was found between the study groups (P value = 0.39). Conclusions: The results for the MDS assessment's α parameter corroborated the PR scores, suggesting contrast sensitivity threshold impairment in patients with RVO. No significant difference in ß value was observed, suggesting that adaptability of the visual system is maintained in treated RVO eyes. Translational Relevance: Currently, visual complaints cannot be entirely identified by Snellen visual acuity alone. The MDS offers potentially a more complete look at visual function, by including contrast sensitivity and may be able to quantify changes otherwise overlooked in retinal disease progression.

Hypoperfusion of the deep capillary plexus associated with acute on chronic cocaine use.

PURPOSE: To illustrate a case of decreased perfusion in the deep capillary plexus seen on ocular coherence tomography angiography in a patient with acute on chronic cocaine use. OBSERVATIONS: A 69-year-old male who presented with a sudden loss of vision in his right eye following recent use of cocaine. Ocular coherence tomography of the right eye revealed hyperreflectivity within layers of the retina and ocular coherence tomography angiography showed decreased vascular density and flow in the deep capillary plexus. CONCLUSIONS AND IMPORTANCE: Cocaine use has been associated with systemic and cardiac effects, as well as ocular sequelae. It has been hypothesized to have a role in the pathogenesis of acute macular neuroretinopathy. Here we present the first case of ocular coherence tomography angiography findings of hypoperfusion of the deep capillary plexus in a patient with acute on chronic cocaine use.

Medication Burden for Patients With Bacterial Keratitis.

PURPOSE: To understand medication use and patient burden for treatment of bacterial keratitis (BK). METHODS: A retrospective study was conducted examining medical records of adult patients with BK in an academic cornea practice. Data collected included medications used in the treatment of BK, dosing of medications, and the number and total duration of clinical encounters. Costs of medications were estimated using the average wholesale pharmacy price. Linear regression analysis was used to investigate associations of medication use with patient demographics and corneal culture results and reported with beta estimates (ß) and 95% confidence intervals (95% CIs). RESULTS: Forty-eight patients with BK (56% female) were studied. Patients were treated for a median of 54 days with 10 visits, 5 unique medications, 587 drops, and 7 prescriptions. The estimated median medication cost was $933 (interquartile range: $457-$1422) US dollars. Positive bacterial growth was significantly associated with more visits (ß: 6.16, 95% CI: 1.75-10.6, P = 0.007), more days of treatment (ß: 86.8, 95% CI: 10.8-163, P = 0.026), more prescribed medications (ß: 2.86, 95% CI: 1.04-4.67, P = 0.003), and more doses of medications (ß: 796, 95% CI: 818-1412, P = 0.012) compared with patients who did not undergo corneal scraping. Patients were prescribed 132 more drops of medication for every 10 years of older age (ß: 132, 95% CI: 18.2-246, P = 0.024). Sex and income were not associated with medication burden or treatment length. CONCLUSIONS: Older patients and those with positive cultures incur the most medication burden in treatment of BK. Providers should be aware of medication usage and cost burden as it may affect compliance with treatment.

Daily Minutes of Unprotected Sun Exposure (MUSE) Inventory: Measure description and comparisons to UVR sensor and sun protection survey data.

One in five US adults will be diagnosed with skin cancer. As most skin cancers are attributable to sun exposure, this risk factor is an important target for research and intervention. Most sun exposure measures assess frequency of specific sun-protection behaviors, which does not account for the use of multiple, potentially overlapping sun-protection methods. In contrast, the Daily Minutes of Unprotected Sun Exposure (MUSE) Inventory assesses sun-protection behavior during self-reported activities, providing several useful metrics, including duration of unprotected sun exposure on 17 body sites, combined to yield an overall MUSE score weighted by percent of body exposed. The present study was conducted July-September 2017, in Chicago, IL USA. For 10 days, participants (39 melanoma survivors; Mage = 58.59, 64.5% female) wore an ultraviolet radiation (UVR) sensor and completed the Daily MUSE Inventory each evening. The Sun Habits Survey was completed at the end of the study. Outdoor time reported in the MUSE Inventory significantly predicted outdoor time recorded by UVR sensors, B = 0.53, p < .001. For all sun-protection behaviors except shade, reports from the Daily MUSE Inventory (i.e., percentage of outdoor time a particular strategy was used) correlated with frequency ratings of the same strategy from the Sun Habits Survey (rs = 0.66-0.75, p < .05). In sum, the Daily MUSE Inventory corresponds with sensor and survey data, and provides a novel metric of unprotected sun exposure that will be useful for evaluating overall extent of sun exposure, including exposure on several smaller body sites that are at high risk for skin cancer.

Using a 3D Culture System to Differentiate Visceral Adipocytes In Vitro.

It has long been recognized that body fat distribution and regional adiposity play a major role in the control of metabolic homeostasis. However, the ability to study and compare the cell autonomous regulation and response of adipocytes from different fat depots has been hampered by the difficulty of inducing preadipocytes isolated from the visceral depot to differentiate into mature adipocytes in culture. Here, we present an easily created 3-dimensional (3D) culture system that can be used to differentiate preadipocytes from the visceral depot as robustly as those from the sc depot. The cells differentiated in these 3D collagen gels are mature adipocytes that retain depot-specific characteristics, as determined by imaging, gene expression, and functional assays. This 3D culture system therefore allows for study of the development and function of adipocytes from both depots in vitro and may ultimately lead to a greater understanding of site-specific functional differences of adipose tissues to metabolic dysregulation.