Demographic Characteristics, Clinical Presentations, and Risk Factors Impacting Visual Outcomes in Peripheral Ulcerative Keratitis.

PURPOSE: To assess the demographic characteristics, ophthalmic and systemic presentations, and risk factors impacting the outcomes in patients diagnosed with peripheral ulcerative keratitis (PUK). METHODS: This retrospective study includes patients diagnosed with PUK at a tertiary care center over 13 years. A descriptive analysis of the demographics, clinical history, and presentation was performed. A reverse risk analysis was performed to assess the PUK resolution in patients with underlying autoimmune and non-autoimmune etiologies. Finally, we evaluated the correlation between treatment duration and final best corrected visual acuity (BCVA) and continuous and categorical variables. RESULTS: A total of 58 eyes of 51 patients with a mean age of 59.67 ± 13.41 years diagnosed with PUK were included in the study; 58.82% were female. The resolution duration was significantly shorter in patients with autoimmune etiologies (vs. non-autoimmune etiologies, P = 0.028) and female patients (vs. male patients, P = 0.008). The BCVA worsened in patients with non-autoimmune etiologies after treatment (P = 0.17). Despite worse BCVA at presentation in patients with underlying autoimmune etiologies, significantly better final vision outcomes were observed (P = 0.04). Linear regression analysis showed that longer treatment duration (P = 0.001; R2 = 0.1704) and worse vision (P = 0.002; R2 = 0.1502) at presentation were the primary risk factors of poor vision outcomes. Similarly, the treatment duration was significantly longer in male compared with female patients (P < 0.001; R2 = 0.2027). CONCLUSIONS: The clinical outcomes in PUK with underlying autoimmune disorders were observed to be better than non-autoimmune etiologies, which may be attributed to the early detection of the PUK-related changes and aggressive medical management. A delayed diagnosis of PUK leads to poor vision outcomes.

Effect of a Patient Portal Reminder Message After No-Show on Appointment Reattendance in Ophthalmology: A Randomized Clinical Trial.

PURPOSE: To assess the efficacy of electronic health record (EHR) messaging for re-engaging patients with ophthalmology care after a missed appointment. DESIGN: Prospective, randomized clinical trial. METHODS: The study setting was an academic ophthalmology department. The patient population comprised of return patients age 18 years or older with an appointment "no show," or missed appointment. Over 2 phases of recruitment, 362 patients with an active patient portal in the EHR were selected consecutively each business day. Patients were randomized using a web-based tool to receive a reminder to reschedule via a standard mailed letter only (control) or the mailed letter plus an electronic message through the EHR within 1 business day of the missed appointment (intervention). Reengagement with eye care was defined as attendance of a rescheduled appointment within 30 days of the no-show visit. Patient charts were reviewed for demographic and clinical data. RESULTS: The average age of recruited patients was 59.9 years, just under half of the sample was male (42.5%, 154/362), and most patients were White (56.9%, 206/362) or Black (36.2%, 131/362). Patients were most commonly recruited from the retina service (39.2%, 142/362) followed by the glaucoma service (29.3%, 106/362). Many patients in this study had previous no-show appointments, with an average no-show rate of 18.8% out of all scheduled visits across our health system. In total, 22.2% (42/189) of patients in the intervention group attended a follow-up appointment within 30 days of their no-show visit compared to 11.6% (20/173) of the control group (OR, 2.186; 95% CI, 1.225-3.898; P = .008). When including only the 74 patients in the intervention group who read the intervention message in the patient portal, 28.4% (21/74) attended a follow-up compared to 11.6% (20/173) of the control group (P = .001). CONCLUSIONS: EHR-based reminder messages sent within a business day of a missed appointment may promote re-engagement in ophthalmology care after appointment no-show.

A rise in the frequency of lasR mutant Pseudomonas aeruginosa among keratitis isolates between 1993 and 2021.

Introduction: Pseudomonas aeruginosa causes vision threatening keratitis. The LasR transcription factor regulates virulence factors in response to the quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone. P. aeruginosa isolates with lasR mutations are characterized by an iridescent high sheen phenotype caused by a build-up of 2-heptyl-4-quinolone. A previous study demonstrated 22% (n=101) of P. aeruginosa keratitis isolates from India between 2010 and 2016 were sheen positive lasR mutants, and the sheen phenotype correlated with worse clinical outcomes for patients. In this study, a longitudinal collection of P. aeruginosa keratitis isolates from Eastern North America were screened for lasR mutations by the sheen phenotype and sequencing of the lasR gene. Methods: Keratitis isolates (n=399) were classified by sheen phenotype. The lasR gene was cloned from a subset of isolates, sequenced, and tested for loss of function or dominant-negative status based on an azocasein protease assay. A retrospective chart review compared outcomes of keratitis patients infected by sheen positive and negative isolates. Results: A significant increase in sheen positive isolates was observed between 1993 and 2021. Extracellular protease activity was reduced among the sheen positive isolates and a defined lasR mutant. Cloned lasR alleles from the sheen positive isolates were loss of function or dominant negative and differed in sequence from previously reported ocular lasR mutant alleles. Retrospective analysis of patient information suggested significantly better visual outcomes for patients infected by sheen positive isolates. Discussion: These results indicate an increase in lasR mutations among keratitis isolates in the United States and suggest that endemic lasR mutants can cause keratitis.

Rise in frequency of lasR mutant Pseudomonas aeruginosa among keratitis isolates between 1993 and 2021.

Pseudomonas aeruginosa causes severe vision threatening keratitis. LasR is a transcription factor that regulates virulence associated genes in response to the quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone. P. aeruginosa isolates with lasR mutations are characterized by an iridescent high sheen phenotype caused by a build-up of 2-heptyl-4-quinolone. A previous study indicated a high proportion (22 out of 101) of P. aeruginosa keratitis isolates from India between 2010 and 2016 were sheen positive and had mutations in the lasR gene, and the sheen phenotype correlated with worse clinical outcomes for patients. In this study, a longitudinal collection of P. aeruginosa keratitis isolates from Eastern North America were screened for lasR mutations by the sheen phenotype and sequencing of the lasR gene. A significant increase in the frequency of isolates with the sheen positive phenotype was observed in isolates between 1993 and 2021. Extracellular protease activity was lower among the sheen positive isolates and a defined lasR mutant. Cloned lasR alleles from the sheen positive isolates were loss of function or dominant negative and differed in sequence from previously reported ocular lasR mutant alleles. Insertion elements were present in a subset of independent isolates and may represent an endemic source from some of the isolates. Retrospective analysis of patient information suggested significantly better visual outcomes for patients with infected by sheen positive isolates. Together, these results indicate an increasing trend towards lasR mutations among keratitis isolates at a tertiary eye care hospital in the United States.

Clinical Characterization and Outcomes of Culture- and Polymerase Chain Reaction-Negative Cases of Infectious Keratitis.

PURPOSE: To examine the clinical presentation, management, and outcomes of culture and polymerase chain reaction (PCR) negative cases of infectious keratitis. METHODS: In this retrospective case series, we evaluated the laboratory and medical records of culture- and PCR-negative cases (2016-2020) reported to a tertiary care center, which were presumed to be infectious keratitis on the basis of clinical history and presentation. RESULTS: A total of 121 cases with culture-negative keratitis were included in this study. The mean age of the patients was 48.42 ± 1.89 years, and 53.72% were female. At presentation, the presumed etiology was viral in 38.01%, bacterial in 27.27%, fungal in 8.26%, Acanthamoeba in 6.61%, and unlisted in 28.92% of cases. The most common risk factors were a previous history of ocular surface diseases (96.69%) and contact lens use (37.19%). In total, 61.98% of the patients were already on antimicrobial medication at presentation. The initial management was altered in 79 cases (65.29%) during the treatment course. Average presenting and final (post-treatment) visual acuities (VA) were 0.98 ± 0.04 (LogMAR) and 0.42 ± 0.03 (LogMAR), respectively. A significantly higher frequency of patients with a final VA worse than 20/40 (Snellen) had worse VA at initial presentation (p < 0.0001). A history of ocular surface disease, cold sores, and recurrent infection (p < 0.05) were more commonly associated with a presumed diagnosis of viral keratitis. The patients with presumed bacterial etiology were younger and had a history of poor contact lens hygiene (p < 0.05). CONCLUSIONS: We observed a distinct difference in clinical features among patients with culture-negative and PCR-negative keratitis managed for presumed viral and bacterial infections. Although there was significant variability in presentation and management duration in this cohort, the visual outcomes were generally favorable.

OCT Angiography in Noninfectious Uveitis: A Description of Five Cases and Clinical Applications.

BACKGROUND: Optical coherence tomography angiography (OCTA) is a noninvasive imaging modality used to analyze the retinochoroidal vasculature and detect vascular flow. The resulting images can be segmented to view each vascular plexus individually. While fluorescein angiography is still the gold standard for the diagnosis of posterior uveitis, it has limitations, and can be replaced by OCTA in some cases. METHODS: This case series describes five patients with posterior noninfectious uveitis and their description by OCTA. RESULTS: Cases included lupus retinopathy (n = 1) for which OCTA showed ischemic maculopathy as areas of flow deficit at the superficial and deep capillary plexus; choroidal granulomas (n = 1) with a non-detectable flow signal in the choroid; active punctate inner choroiditis and multifocal choroiditis (n = 1) with OCTA that showed active inflammatory chorioretinal lesions as non-detectable flow signals in choriocapillaris and choroid; dense type 2 inflammatory secondary neovascularization (n = 1) associated with active choroiditis; and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1) without flow abnormalities at the superficial and deep retinal plexuses but non-detectable flow at the levels of the choriocapillaris and choroid. CONCLUSIONS: Ophthalmologists can use OCTA to identify inflammatory changes in retinal and choroidal vasculature, aiding in the diagnosis, management, and monitoring of posterior uveitis.

Characteristics associated with barriers to eye care: A cross-sectional survey at a free vision screening event.

INTRODUCTION: Social determinants of health can limit access to regular eye care, but their role in ophthalmology is underexamined. The purpose of this study is to assess the relationship between patient characteristics and self-reported barriers to eye care. METHODS: This anonymous, cross-sectional survey was conducted at a two-day free eye clinic event in Pittsburgh, Pennsylvania. Adult patients presenting for vision screening were eligible to participate. Patient characteristics (demographics, health status) and self-reported barriers to eye care were collected. Predictors of barriers to eye care were analyzed using binary logistic regression. RESULTS: Of 269 eligible, consecutive patients approached for survey completion, 183 comprised the volunteer sample. The 183 participants (105 female patients [59%]) had a mean (standard deviation) age of 53 (15) years, and generally self-identified as Black (74, 46%) or White (67, 41%). While a third reported having no health insurance (60, 34%), the remaining two-thirds of participants had public (84, 48%) or private coverage (34, 19%). Three-quarters of respondents reported at least one barrier to receiving regular eye care (136, 76%), most commonly medical costs (89, 50%) and insurance issues (73, 41%). Not having health insurance or vision insurance was strongly associated with reporting at least one barrier to care (OR 5.00, p=0.002, and OR 7.46, p<0.001, respectively). Those with self-reported eye disease were more likely to report transportation difficulties (OR 4.45, p=0.013), and employed participants reported difficulty getting time off work to attend eye exams (OR 7.73, p=0.002). Finally, compared to Black race, White race was associated with a higher likelihood of reporting any barrier to care (OR 2.79, p=0.013). CONCLUSION: Three-quarters of vision screening attendees reported at least one barrier to regular eye care, most commonly medical costs and insurance.

Fungal Keratitis: Clinical Features, Risk Factors, Treatment, and Outcomes.

Fungal keratitis (FK) can be challenging to diagnose and treat. In this retrospective case series, FK cases presenting at the University of Pittsburgh Medical Center, Pennsylvania, USA, from 2015 to 2021 were reviewed for ocular risk factors, clinical presentation, management, and outcomes. Twenty-eight cases of FK were included. The median presenting age was 58.5 (18.5) years, and the median symptom duration prior to presentation was 10 (35.8) days. Predisposing ocular risk factors included contact lens use (67.9%), recent ocular trauma/abrasion (42.9%), and history of ocular surgery (42.9%). The median presenting visual acuity (VA) was 1.35 (1.72) LogMAR. About half presented with a central ulcer (42.9%), large infiltrate (6.7 (6.3) mm2), corneal thinning (50.0%), and hypopyon (32.1%). The majority of isolated fungal species were filamentous (75.0%). Most common antifungal medications included topical voriconazole (71.4%) and natamycin (53.6%) drops and oral voriconazole (64.3%). Surgical management was necessary in 32.1% of cases and enucleation in one case. Defect resolution occurred in 42.5 (47.0) days, and median final VA was 0.5 (1.84) LogMAR. Features associated with poor final visual outcomes included poor initial VA (p < 0.001) and larger defect size (p = 0.002). In conclusion, unlike prior studies in the northeast region of the USA, FK was commonly caused by filamentous fungi, and antifungal management most often consisted of topical and oral voriconazole.

The Use of Mobile Messaging for Telecommunications with Patients in Ophthalmology: A Systematic Review.

Introduction: Communication and concordance between patients and providers are crucial for improved outcomes and disease prevention. Mobile health strategies have been shown to improve patient accessibility and convenience. Mobile messaging is one strategy that has demonstrated varying degrees of effectiveness in patient care. The aim of this review is to investigate methods, outcomes, and conclusions of studies that have assessed mobile messaging interventions in ophthalmology. Methods: A qualitative systematic review of PubMed, Scopus, Web of Science, and Embase databases was conducted to identify studies that investigated the implementation and efficacy of mobile messaging services in ophthalmology practice. Included articles were categorized based on study content: appointment attendance, patient preference and willingness, education, concordance, and other clinical outcomes. Three tools were used to assess for potential bias. Results: Out of a total of 3,655 unique titles retrieved, 15 articles were included in the final qualitative synthesis after abstract and full-text screening. Included studies were published between 2008 and 2020 from seven different countries and across various contexts. All but one study found that the use of mobile messaging in ophthalmology care led to improved process measures or patient outcomes. Evidence for a positive effect was the strongest for appointment follow-up. Survey and feedback data suggest that patients, more so younger patients, are open to mobile message interventions. Conclusion: Mobile messaging interventions can play a role in improving appointment attendance, patient education, and patient practices for ophthalmology patients. Further study is necessary to determine the effectiveness of this tool across various groups and settings.

Microbiological evaluation of corneal and contact lens cultures in contact lens-associated bacterial keratitis.

PURPOSE: To determine the degree of microbiological agreement between corneal scrapings and contact lens cultures in cases of contact lens-associated keratitis. METHODS: Electronic medical records of all cases of contact lens-associated keratitis at a single institution from April 2006 to May 2019 were reviewed. Cases where both corneal scrapings and contact lens cultures were obtained were included in the study. Group 1 demonstrated agreement between corneal scrapings and contact lens cultures. Group 2 demonstrated growth on both cultures, but disagreement in isolated organism. Group 3 demonstrated negative corneal cultures but growth on contact lens cultures and the diagnostic yield of contact lens microbiological cultures and agreement between corneal and contact lens cultures. RESULTS: A total of 80 eyes of 72 patients were included in the study. 135 total incidences of microbiological results were included for data analysis. Group 1 contained nine incidences (6.7%), group 2 contained 60 incidences (44.4%) and group 3 contained 66 incidences (49%). In group 3, 50% of the cases were treated based on contact lens culture data. There was no statistically significant difference between all three groups in terms of baseline characteristics, presenting vision, vision at last follow-up, number of antibiotics used or complications from keratitis. Pseudomonas was the most common microorganism isolated, and in 89% of these cases, there was disagreement between corneal and contact lens cultures. CONCLUSIONS: Although there was a disagreement in the microbiological yield between contact lens and corneal cultures, contact lens cultures were useful in management of patients while achieving similar outcomes.

An 18-Year Overview of Serratia marcescens Ocular Infection.

PURPOSE: Serratia marcescens is a frequent ocular bacterial pathogen implicated in keratitis, endophthalmitis, and conjunctivitis. We evaluated the risk factors and treatment outcomes of ocular infections due to S. marcescens. METHODS: In this retrospective observational study, all S. marcescens-positive cases between February 2002 and February 2020 were reviewed for ocular risk factors that included log of minimal angle of resolution visual acuity (VA), medical management, and time to epithelial defect closure. RESULTS: Fifty-one patients were identified (72.5% females, 46.8±23.3 years). Forty-six patients had complete medical records, and 5 had microbiology data available. The most prevalent ocular risk factors were, contact lens (CL) use (68.6%), corneal disease (52.9%), and history of ocular surgery (41.2%). Mean presenting VA was 1.3±1.0. About half of the patients presented with a central ulcer (49%, 25), large infiltrate (20.4±31.8 mm2 mean), and hypopyon (43.1%, 22). All cases were reported to be susceptible to ciprofloxacin. Defect closure occurred in 52.3±117.1 days and final VA was 0.86±0.88. Adjunctive treatments were required in 14 cases (27.5%). One patient underwent surgical intervention. Features associated with poor VA outcomes included, history of glaucoma (P=0.038), older age at presentation (P<0.001), presence of hypopyon (0.045), poor VA at presentation (0.0086), time to epithelial defect closure (0.0196), and large infiltrate size (P=0.0345). CONCLUSIONS: S. marcescens keratitis and conjunctivitis is associated with CL use and history of ocular surface disease. Worse outcomes were associated with older age, infiltrate size, presence of hypopyon, worse initial VA, longer time to epithelial defect closure, and history of glaucoma.

3D-Reconstruction of the human conventional outflow system by ribbon scanning confocal microscopy.

PURPOSE: The risk for glaucoma is driven by the microanatomy and function of the anterior segment. We performed a computation-intense, high-resolution, full-thickness ribbon-scanning confocal microscopy (RSCM) of the outflow tract of two human eyes. We hypothesized this would reveal important species differences when compared to existing data of porcine eyes, an animal that does not spontaneously develop glaucoma. METHODS: After perfusing two human octogenarian eyes with lectin-fluorophore conjugate and optical clearance with benzyl alcohol benzyl benzoate (BABB), anterior segments were scanned by RSCM and reconstructed in 3D for whole-specimen rendering. Morphometric analyses of the outflow tract were performed for the trabecular meshwork (TM), limbal, and perilimbal outflow structures and compared to existing porcine data. RESULTS: RSCM provided high-resolution data for IMARIS-based surface reconstruction of outflow tract structures in 3D. Different from porcine eyes with an abundance of highly interconnected, narrow, and short collector channels (CCs), human eyes demonstrated fewer CCs which had a 1.5x greater cross-sectional area (CSA) and 2.6x greater length. Proximal CC openings at the level of Schlemm's canal (SC) had a 1.3x larger CSA than distal openings into the scleral vascular plexus (SVP). CCs were 10.2x smaller in volume than the receiving SVP vessels. Axenfeld loops, projections of the long ciliary nerve, were also visualized. CONCLUSION: In this high-resolution, volumetric RSCM analysis, human eyes had far fewer outflow tract vessels than porcine eyes. Human CCs spanned several clock-hours and were larger than in porcine eyes. These species differences may point to factors downstream of the TM that increase our vulnerability to glaucoma.

Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract.

PURPOSE: To characterize the effects of netarsudil on the aqueous humor outflow tract distal to the trabecular meshwork (TM). We hypothesized that netarsudil increases outflow facility in eyes with and without circumferential ab interno trabeculectomy (AIT) that removes the TM. METHODS: Sixty-four porcine anterior segment cultures were randomly assigned to groups with (n = 32) and without circumferential AIT (n = 32). Cultures were exposed to 0.1, 1, and 10 µM netarsudil (N = 8 eyes per concentration). For each concentration, IOP and vessel diameters were compared with their respective pretreatment baselines. Outflow tract vessel diameters were assessed by spectral-domain optical coherence tomography (SDOCT) and rendered in 4D (XYZ time series). RESULTS: Netarsudil at 1 µM reduced IOP both in eyes with TM (- 0.60 ± 0.24 mmHg, p = 0.01) and in eyes without TM (- 1.79 ± 0.42 mmHg, p < 0.01). At this concentration, vessels of the distal outflow tract dilated by 72%. However, at 0.1 µM netarsudil elevated IOP in eyes with TM (1.59 ± 0.36 mmHg, p < 0.001) as well as in eyes without TM (0.23 ± 0.32 mmHg, p < 0.001). Vessels of the distal outflow tract constricted by 31%. Similarly, netarsudil at a concentration of 10 µM elevated IOP both in eyes with TM (1.91 ± 0.193, p < 0.001) and in eyes without TM (3.65 ± 0.86 mmHg, p < 0.001). At this concentration, outflow tract vessels constricted by 27%. CONCLUSION: In the porcine anterior segment culture, the dose-dependent IOP changes caused by netarsudil matched the diameter changes of distal outflow tract vessels. Hyper- and hypotensive properties of netarsudil persisted after TM removal.

Intraocular pressure reduction in a pigmentary glaucoma model by Goniotome Ab interno trabeculectomy.

PURPOSE: To investigate whether microsurgical excision of trabecular meshwork (TM) in an ex vivo pigmentary glaucoma model can normalize the hypertensive phenotype. METHODS: Eight eyes of a porcine pigmentary glaucoma model underwent 90° of microsurgical TM excision with an aspirating dual-blade (Goniotome (G)). 24 hours later, additional 90° of TM were removed. Anterior segments with sham surgeries served as the control (C). Outflow facility and intraocular pressure (IOP) were analyzed. Histology with hematoxylin and eosin (H&E) was obtained. RESULTS: After the first 90° TM excision, IOP was significantly lower in G (10.2±2.4 mmHg, n = 7) than C (20.0±2.0mmHg, n = 8, P<0.01). Outflow facility in G (0.38±0.07 µl/min/mmHg) was higher than C (0.16±0.02 µl/min/mmHg, P<0.01). After the second 90° TM excision, IOP in G (6.46±0.81 mmHg, n = 7) was significantly lower than C (20.3±1.7 mmHg, n = 8, P<0.001), while the outflow facility in G (0.50±0.05 µl/min/mmHg, n = 7) was higher than C (0.16±0.01 µl/min/mmHg, n = 8, P<0.001). Compared to the first excision, excision of an additional 90° did not change of IOP (P = 0.20) or outflow facility (P = 0.17) further. CONCLUSIONS: Excision of 90° of TM in a pigmentary glaucoma model using an aspirating dual-blade decreased IOP and increased outflow facility.

Methicillin-Resistant Staphylococcus aureus Keratitis: Initial Treatment, Risk Factors, Clinical Features, and Treatment Outcomes.

PURPOSE: To analyze the clinical characteristics, management choices, and outcomes of cases of methicillin-resistant Staphylococcus aureus (MRSA) keratitis. DESIGN: Retrospective interventional case series. METHODS: Fifty-two culture-proven (52 eyes) cases of MRSA keratitis diagnosed and treated at the University of Pittsburgh Medical Center were identified and reviewed. RESULTS: The mean age was 66.6 ± 19.2 years with a median follow-up time of 147 days. The most prevalent risk factors included a history of ocular surgery (62.5%), topical corticosteroid use (35.4%), and dry eye syndrome (37.5%). There was a high burden of systemic disease (95.8%). The average presenting logarithm of minimal angle of resolution visual acuity was 1.7 ± 0.8 and the average final logarithm of minimal angle of resolution visual acuity was 1.2 + 1.0. Initial antibiotic treatment varied, with 20.8% receiving moxifloxacin alone, 20.8% receiving fortified cefazolin and fortified tobramycin together, and 12.5% receiving fortified vancomycin and fortified tobramycin, although other antibiotics were used during treatment if warranted. Surgical management was often required as 17.3% of eyes perforated: 13.5% required tarsorrhaphy, 5.8% required penetrating keratoplasty, and 1 eye was enucleated. When patients treated with fourth-generation fluoroquinolones were compared with those treated with fortified vancomycin, no difference in final visual acuity, treatment duration, or need for surgery was found. CONCLUSION: MRSA causes fulminant keratitis often requiring surgical management with poor visual acuity outcomes. Poor ocular surface, topical corticosteroid use, previous ocular surgery, and/or a high burden of systemic disease were identified as common risk factors. Patients treated with fluoroquinolones in our study had comparable outcomes to those treated with fortified vancomycin; however, those treated with fortified vancomycin tended to have more severe ulcers at presentation.