Secondary bacterial corneal infection caused by Myroides species in primary fungal keratitis.

A middle-aged male patient presented with a central corneal perforation in a deep stromal infiltrate in his left eye. An emergency therapeutic penetrating keratoplasty was performed. Microbiological evaluation of the corneal scraping specimen revealed septate fungal filaments on stains. However, culture reports after 24 hours from the scraping sample and the excised half corneal button showed growth of gram-negative bacilli. This pathogen was identified as an aerobic, non-fermentative, gram-negative, bacillus by conventional microbiology and confirmed as Myroides species by the VITEK 2 Compact system (bioMérieux, Marcy l'Etoile, France). Susceptibility to chloramphenicol was noted based on which the patient was treated with topical chloramphenicol 0.5%. No recurrence of the infection was noted. This is the first reported case of corneal infection with the Myroides species of bacteria which, heretofore, have been known to cause endocarditis and urinary tract infections.

Multiple conjunctival autografts from the contralateral eye for management of recurrent symblepharon in eyes with unilateral chemical burn.

We present two cases which underwent complex ocular surface reconstruction to achieve a stable ocular surface. Conjunctival autograft (CAG) procedure was required more than once, in addition to simple limbal epithelial transplantation to address extensive symblepharon in the eyes with total unilateral limbal stem cell deficiency secondary to acid ocular burns. These cases demonstrate that multiple CAGs may be harvested from the contralateral unaffected eye to correct recurrent symblepharon without any donor site complications if the correct surgical technique is adopted.

Neutrophil-driven and interleukin-36γ-associated ocular surface inflammation in chronic Stevens-Johnson syndrome.

PURPOSE: This study aims to elucidate the tear proteome and understand the underlying molecular mechanisms involved in the ocular complications following Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: Mass spectrometry (MS) was performed to quantify the tear fluid proteins from chronic SJS/TEN patients (n = 22 eyes) and age- and gender-matched controls (n = 22 eyes). The candidate proteins were validated using ELISA (n = 80 eyes) in tear samples and immunohistochemistry (IHC; n = 12) in eyelid margin specimens. These proteins were compared for significant differences based on age, gender, disease duration, and ocular severity. RESULTS: A total of 1692 tear fluid proteins were identified, of which 470 were significantly differentially regulated in chronic SJS/TEN. The top 10 significantly upregulated proteins were neutrophil secretions including neutrophil elastase (p < .0001), defensin (p < .0001), and matrix metalloproteinase 8 (p < .0001). The presence of neutrophils was confirmed by the upregulation of IL-8 (p < .001) in tears, a key cytokine known for recruiting neutrophils. Additionally, positive expression of myeloperoxidase was observed in the keratinized eyelid margins of SJS/TEN to validate the presence of neutrophils. Among 41 unique proteins identified by MS, IL-36γ (p < .01) was expressed in three SJS/TEN patients and was confirmed in SJS/TEN tears and eyelid margins by ELISA and IHC, respectively. IL-36γ was specifically expressed in the superficial layers of eyelid margin keratinized conjunctiva. The majority of the significantly downregulated proteins were lacrimal gland secretions such as lacritin (p < .0001) and opiorphin (p < .002). Neutrophil elastase (p < .02) was significantly elevated in patients with severe eyelid margin keratinization. CONCLUSION: Our observations indicate a clear correlation between eyelid margin keratinization and the expression of IL-36γ, potentially mediated by neutrophils recruited via IL-8. Future experimental studies are needed to test the role of therapies targeting IL-8 and/or IL-36γ in reducing eyelid margin keratinization and its associated ocular complications in SJS/TEN.

Amplification of Mutant NRAS in Melanocytic Tumors With Features of Spitz Tumors.

NRAS activating mutations are prevalent in melanocytic neoplasia, occurring in a subset of common acquired melanocytic nevi and ∼30% of cutaneous melanomas. In this study, we described a cohort of 7 distinctive melanocytic tumors characterized by activating point mutations in codon 61 of NRAS with amplification of the mutant NRAS allele and shared clinicopathologic features. These tumors occurred predominantly in younger patients, with a median age of 20 years (range, 6-56 years). They presented as papules on the helix of the ear (4 cases) or extremities (3 cases). Microscopically, the tumors were cellular, relatively well-circumscribed, compound, or intradermal proliferations. The tumor cells often extended into the deep reticular dermis and involved the superficial subcutaneous fat in some cases. The melanocytes were epithelioid to spindled with moderate amounts of cytoplasm and conspicuous nucleoli. They were arranged in short plexiform fascicles, nests, and cords. Some cases had occasional pleomorphic and multinucleated melanocytes. Rare dermal mitotic figures were present in all cases. The dermis contained thick collagen bundles and minimal solar elastosis. Follow-up data were available for 5 patients, with a median period of 4.2 years (range, 1-9 years), during which no recurrences or metastases were reported. Our series highlights a clinicopathologically and molecularly distinctive subset of NRAS-mutated tumors with amplification of the mutant NRAS allele.

Long-term outcomes of glued (sutureless) amniotic membrane transplantation in acute Stevens-Johnson syndrome/toxic epidermal necrolysis: a comparative study.

PURPOSE: To compare the effectiveness and efficiency of a glued (sutureless) technique for amniotic membrane transplantation (AMT) with a traditional sutured one in the setting of acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: This retrospective cohort study evaluated all patients diagnosed with SJS/TEN between 2008 and 2020 within our hospital network who received AMT in the acute phase according to our protocol and had at least one ophthalmic follow-up in the chronic phase. Primary outcomes included best-corrected visual acuity (BCVA) at the most recent visit, presence of a severe ocular complication (SOC) via predefined criteria, time to procedure and duration of procedure. Random effects model analysis was used to evaluate the impact of potential covariates on outcome measures. RESULTS: A total of 23 patients (45 eyes) were included: 14 patients (27 eyes) in the AMT suture group and 9 patients (18 eyes) in the AMT glue group. There was no difference between the two groups in BCVA at the most recent visit (p=0.5112) or development of a SOC (p=1.000). The glue method was shorter in duration than the suture method (p<0.001). Random effects model additionally indicated that there was no difference in BCVA at most recent follow-up between patients who had received glued versus sutured AMT (p=0.1460). CONCLUSIONS: Our glued technique for AMT is as effective as our sutured technique in stabilising the ocular surface and mitigating chronic ocular complications in SJS/TEN. The glued technique is also shorter in duration and performed more expediently than the sutured technique.

Clinical profile and management of ocular superglue injuries: Case series and review of literature.

PURPOSE: To describe the clinical profile and management of patients with ocular superglue injury (OSI). METHODS: This retrospective study included all patients with OSI who presented at a tertiary eye care institute between 2016 and 2020. Data regarding demographics, clinical profile, and management were collected. RESULTS: A total of 66 eyes of 58 patients (24 children, 34 adults) with a median age of 22.5 years [interquartile range (IQR): 11.3-31] were included. All cases sustained accidental injuries, with domestic injury at home being the most common location of injury among children (79%) and adults (53%) ( P = 0.39). The median visual acuity at presentation was worse in children [0.3 logMAR (IQR: 0.2-0.4)] as compared to adults [0.1 logMAR (IQR: 0.1-0.3)] ( P = 0.03)]. The most common clinical sign at presentation was conjunctival congestion in 77% of eyes (51/66) followed by polymerized glue stuck to the eyelashes and eyelids in 52% of eyes (34/66). The median duration from the time of injury to presentation was 2 hours in both groups. All eyes resolved with medical management. Examination under anesthesia was required in three children (13%) to evaluate the extent of OSI. None of the patients had long-term ocular complications. CONCLUSION: Improper and careless handling of superglue in the domestic setting may cause accidental ocular injuries that require immediate medical attention. OSI represents less severe ocular injuries that respond to medical therapy alone and is not associated with long-term visual morbidity. Modifications in the packaging of superglue containers and awareness about their deleterious effects could prevent these injuries.

Pseudopithomyces Maydicus and Phialophora Chinensis Rare Fungal Keratitis: Case Series, DNA Sequencing, Antifungal Susceptibility Patterns.

PURPOSE: We report two cases of fungal keratitis due to rare melanized fungal pathogens in ocular infection, one is the first case report of keratitis due to Pseudopithomyces maydicus and the second is keratitis due to rare fungal pathogen in ocular infections Phialophora chinensis. METHOD: Conventional mycology during routine diagnostics helped in identifying these rare fungal isolates, following which we proceeded for the confirmation of identification by DNA sequencing and did in-vitro antifungal susceptibility test to understand their susceptibility pattern. The clinical information for these two patients were collected from hospital electronic medical records. RESULTS: We discuss the clinical presentation, treatment given, and clinical outcome in these patients and correlate these with the conventional microbiology and sequencing techniques, which helped in identifying the pathogen and the in-vitro antifungal susceptibility of these rare isolates. We also do a brief literature review for these two rare fungal pathogens. CONCLUSIONS: Pseudopithomyces maydicus and Phialophora chinensis are rare causes of fungal keratitis due to melanized fungi. Both of this fungal keratitis respond well to medical therapy alone if diagnosed and treated early.

Direct Immunofluorescence Findings and Factors Affecting Conjunctival Biopsy Positivity in Ocular Mucous Membrane Pemphigoid.

PURPOSE: The aim of this study was to describe the direct immunofluorescence (DIF) findings and factors affecting conjunctival biopsy positivity in patients clinically diagnosed with ocular mucous membrane pemphigoid (OMMP). METHODS: This retrospective observational case series included patients with clinical OMMP who underwent conjunctival biopsy for DIF in at least 1 eye between 2018 and 2021 in an institutional setting. The primary outcome measures were association of age and chronic ocular complications with biopsy positivity. RESULTS: Of 61 patients, DIF positivity was seen in 33 (54.1%) clinically suspected cases of OMMP. Of 39 patients who underwent bilateral biopsy, 23 (59%) were positive, of which 12 (52%) were positive in both eyes while 11 (48%) were positive in 1 eye. Of 22 patients who underwent unilateral biopsy, 10 (45%) were positive. Of the 100 biopsied eyes, 45 (45%) were DIF positive. Among the immunoreactants studied, linear deposition of C3 was seen in all 45 positive eyes (100%). Increasing age was significantly associated with higher likelihood of biopsy negativity ( P = 0.032), whereas a greater Sotozono chronic ocular complication score, indicative of disease severity, was associated with low likelihood of biopsy positivity ( P = 0.0042) and lower overall expression of immunoreactants on DIF ( P = 0.0007). CONCLUSIONS: Older patients and patients with more severe ocular surface disease sequelae are likely to have negative DIF results. To optimize the chances of confirming the diagnosis of OMMP by DIF, both eyes should be biopsied early in the disease course. If 1 eye is being biopsied, the less affected eye must be chosen.

Lead-Free Piezoelectric Energy Harvester Based on 2D Bismuth Titanate.

The use of two-dimensional (2D) layered materials with a noncentrosymmetric structure dramatically increases the potential of nanoscale electromechanical systems and electronic devices. In this work, liquid-phase exfoliation of bulk bismuth titanate was employed to synthesize atomically thin 2D sheets and fabricate a high-performance piezoelectric energy harvester. The structural and morphological properties of the 2D sheets were analyzed, confirming their phase purity and layer formation. Piezoelectric properties of the 2D sheets were evaluated using Piezoresponse Force Microscopy (PFM), demonstrating a high d33 piezoelectric coefficient of 40 pm/V in a few-layer bismuth titanate nanosheet. A prototype energy harvesting device was fabricated with 2D bismuth titanate as the active material. The piezoelectric response of the fabricated device was recorded at different frequencies and forces, which yielded a maximum d33 of 57.8 pC/N at 1 Hz. Such a solid electromechanical performance at a relatively infinitesimal input response indicates that 2D bismuth titanate can be useful for piezoelectric energy harvesting applications.

Impact of Symblepharon Management With Ocular Surface Reconstruction on Scleral Lens Fitting in Eyes With Chronic Cicatrizing Conjunctivitis and Keratopathy.

PURPOSE: The aim of this study was to describe the importance of symblepharon release with ocular surface reconstruction (OSR) for optimal fitting of scleral contact lenses (SCLs) in eyes with chronic cicatrizing conjunctivitis (CCC) and keratopathy. METHODS: This retrospective study included 32 eyes with CCC and keratopathy with symblepharon which underwent symblepharon release with OSR and were fitted with SCLs. The primary outcome measure was the improvement in best-corrected visual acuity with SCL wear. RESULTS: A total of 32 eyes of 29 patients (66% men) with a median age of 30.5 years were included. The common causes of CCC were Stevens-Johnson syndrome (66%) and ocular burns (16%). The most common location of symblepharon was superior (59%) with limbal involvement in most eyes (94%). Symblepharon release was combined with mucous membrane grafting (63%), amniotic membrane grafting (31%), or conjunctival autografting (6%). The median interval between symblepharon release with OSR and SCL trial was 15 weeks [interquartile range (IQR): 6-24]. The median best-corrected visual acuity improved from logMAR 1.5 (IQR: 1.2-1.8) to logMAR 1.2 (IQR: 0.6-1.4) with SCLs after symblepharon release with OSR (P < 0.001). The median diameter of the SCL used was 15 mm (IQR: 15-16), with a median base curve of 7.9 mm (IQR: 7.9-8). Symblepharon recurrence was noted in 70% of eyes that underwent amniotic membrane grafting; no recurrence was seen with mucous membrane grafting or conjunctival autografting. CONCLUSIONS: In eyes with CCC with keratopathy and symblepharon, visual rehabilitation is possible with SCLs after symblepharon release with OSR without having to resort to a penetrating corneal procedure.

Disease burden among patients with atopic dermatitis treated with systemic therapy for 4-12 months: results from the CorEvitas Atopic Dermatitis Registry.

BACKGROUND: Real-world data on the effectiveness of systemic therapy in atopic dermatitis (AD) are limited. METHODS: Adult patients with AD in the CorEvitas AD registry (2020-2021) who received systemic therapies for 4-12 months prior to enrollment were included based on disease severity: body surface area (BSA) 0%-9% and BSA ≥10%. Demographics, clinical characteristics, and outcomes were assessed using descriptive statistics. Pairwise effect sizes (ES) were used to compare BSA groups. RESULTS: The study included 308 patients (BSA 0%-9%: 246 [80%]; BSA ≥10%: 62 [20%]). Despite systemic therapy, both BSA groups reported the use of additional topical therapy and the presence of lesions at difficult locations. Moderate-to-severe AD (vIGA-AD®) was reported by 11% (BSA 0%-9%) and 66% (BSA ≥10%; ES = 0.56) of patients. Mean disease severity scores: total BSA (2% and 22%; ES = 3.59), EASI (1.1 and 11.1; ES = 2.60), and SCORAD (12.1 and 38.0; ES = 1.99). Mean scores for PROs: DLQI (3.7 and 7.5; ES = 0.75), and peak pruritus (2.2 and 4.5; ES = 0.81). Inadequate control of AD was seen in 27% and 53% of patients (ES = 0.23). CONCLUSIONS: Patients with AD experience a high disease burden despite systemic treatment for 4-12 months. This study provides potential evidence of suboptimal treatment and the need for additional effective treatment options for AD.

This real-world study assessed clinical characteristics and overall disease burden in adult patients with atopic dermatitis (AD) who were receiving systemic therapy for 4­12 months.Patients reported greater involvement of back and anterior trunk, and lesions at difficult locations. Irrespective of body surface area involvement, patients continued to experience inadequate control of AD, varied disease severity, and impact on quality of life.The study provides potential evidence of suboptimal treatment and the need for effective treatment options for the management of AD. Besides clinical outcomes, treating dermatologists and dermatology practitioners should include patient-reported outcomes in routine clinical care to determine the best treatment options for their patients.

Sequelae of carbide-related thermo-chemical injury: A retrospective analysis.

Purpose: To describe the outcomes of eyes with calcium carbide (CaC2)-related thermo-chemical injury. Methods: This study included 28 eyes of 23 patients who presented with calcium carbide-related ocular burns. Only patients with more than three months of follow-up were included. Group A included 16 eyes with Dua's Grade I-III burns, while Group B included 12 eyes with Grade IV-VI burns. Electronic medical records were reviewed to provide data on the etiology of burn, presenting clinical signs and visual acuity, sequelae, and surgical interventions performed, both in the acute and chronic phases. Results: The overall mean age was 28.48 ± 11.8 years. Fifteen patients were injured while using carbide to create an explosion to scare away animals on farms. The median presenting BCVA (best-corrected visual acuity) in Group A (20/160) was significantly better than in Group B [(20/2000) (P = 0.002)]. Five eyes in Group A and one eye in Group B underwent medical management. There was no difference in the duration of follow-up for both groups (P = 0.24). The median final BCVA in Group A (20/32) was significantly better than in Group B [(20/200) (P = 0.02)]. Two eyes in Group A and nine eyes in Group B developed LSCD. Two eyes in Group B were phthisical at the last visit. Conclusion: Calcium carbide-related ocular injuries can result in significant visual morbidity in young adults. Early presentation and management may improve outcomes. Prevention of these injuries by increasing awareness and increasing advocacy efforts is necessary.

Case Report: Simultaneous penetrating keratoplasty with autologous simple limbal epithelial transplantation as an alternative to keratoprosthesis.

Introduction and importance: This case report highlights the multidisciplinary approach required to achieve successful anatomical and functional outcomes, in an eye with total limbal stem cell deficiency (LSCD) associated with underlying corneal scarring and thinning. Presentation of case: A 59-year-old gentleman had poor visual recovery in the right eye (RE) following accidental carbide blast, 1-year before presenting to us. The visual acuity was counting fingers and clinical examination revealed cicatricial entropion involving the upper eyelid, total LSCD, corneal scarring with a central descemetocele and cataract in the RE. Prior to ocular surface reconstruction, entropion correction was performed. Three months later, penetrating keratoplasty combined with cataract surgery and intraocular lens implantation (penetrating keratoplasty (PK) triple), with autologous simple limbal epithelial transplantation (SLET) was performed. The visual acuity was 20/100, 18 months after the surgery, with a clear well-epithelized corneal graft and stable ocular surface. Discussion: LSCD is caused by a decrease in the population and /or function of the limbal epithelial stem cells. Limbal stem cell transplantation (LSCT) is warranted in eyes with total LSCD. In eyes with coexisting corneal scarring, LSCT alone may be inadequate to restore the vision. These eyes require simultaneous or sequential lamellar or full-thickness corneal transplantation for visual rehabilitation. Though, the existing literature favors a sequential approach, where LSCT is performed first followed by corneal transplantation, under certain circumstances such as a thin underlying cornea like in our case, corneal transplantation may have to be combined with LSCT to achieve optimal outcomes. Conclusion: Combining autologous SLET with PK can be performed for visual rehabilitation in eyes with unilateral total LSCD and underlying corneal thinning. Corneal and limbal graft survival is prolonged if existing adnexal comorbidities are addressed before any surgical intervention is planned and adequate time interval is allowed for the surface inflammation to subside.

Demographic profile and clinical characteristics of patients presenting with acute ocular burns.

Purpose: To study and compare the demographic and clinical profile of acute ocular burns (AOB) in children and adults. Methods: This retrospective case series included 271 children (338 eyes) and 1300 adults (1809 eyes) who presented to two tertiary eye care centers within one month of sustaining AOB. Data regarding demographics, causative agents, severity of injury, visual acuity (VA), and treatment were collected and analyzed. Results: Males were more commonly affected particularly among adults (81% versus 64%, P < 0.00001). Among children, 79% sustained domestic injuries, whereas 59% of adults had work-place injuries (P < 0.0001). Most cases were due to alkali (38%) and acids (22%). Edible lime (chuna, 32%), superglue (14%), and firecrackers (12%) in children, and chuna (7%), insecticides, lye, superglue (6% each), toilet cleaner (4%) and battery acid (3%) in adults, were the main causative agents. The percentage of cases with Dua grade IV-VI was greater in children (16% versus 9%; P = 0.0001). Amniotic membrane grafting and/or tarsorrhaphy were needed in 36% and 14% of affected eyes in children and adults, respectively (P < 0.00001). The median presenting VA was logMAR 0.5 in children and logMAR 0.3 in adults (P = 0.0001), which improved significantly with treatment in both groups (P < 0.0001), but the final VA in eyes with Dua grade IV-VI burns was poorer in children (logMAR 1.3 versus logMAR 0.8, P = 0.04). Conclusion: The findings clearly delineate the at-risk groups, causative agents, clinical severity, and treatment outcomes of AOB. Increased awareness and data-driven targeted preventive strategies are needed to reduce the avoidable ocular morbidity in AOB.

Vortex Keratopathy as a Presenting Feature of Ocular Mucous Membrane Pemphigoid.

PURPOSE: The aim of this study was to describe the presenting feature of vortex keratopathy in 3 patients with biopsy-proven ocular mucous membrane pemphigoid (OMMP). METHODS: The first patient was a 52-year-old woman with chronic redness and foreign body sensation for 3 years who presented with unilateral vortex keratopathy. Seven months later, in the same eye, she developed conjunctival signs suggestive of OMMP. The second patient was a 33-year-old woman with similar chronic symptoms that were exacerbated by pterygium surgery. Clinical examination revealed vortex keratopathy in the right eye with subtle conjunctival signs suggestive of OMMP. The third patient was a 70-year-old woman with complaints of repeated episodes of redness and foreign body sensation for 18 months who presented with vortex keratopathy in the right eye and conjunctival signs suggestive of OMMP in the same eye. To confirm the clinical diagnosis, bilateral conjunctival biopsy was performed in all patients. RESULTS: OMMP was diagnosed based on conjunctival signs and confirmed on direct immunofluorescence positivity, demonstrating antibodies characteristic and diagnostic of OMMP in the basement membrane zone. A unique feature that preceded or coexisted with the conjunctival signs was unilateral vortex keratopathy seen in all 3 patients, independent of the stage of the disease at which they presented. CONCLUSIONS: Vortex keratopathy can be a presenting feature in patients with OMMP. A complete ocular surface examination, especially checking the medial canthus for keratin and the inferior fornix for foreshortening, is necessary. Conjunctival biopsy should be performed in all cases to confirm the clinical diagnosis wherever required.

Development of PEGylated Cu nanoclusters: A nontoxic, multifunctional colloidal system for bioimaging and peroxide sensing.

This study introduces the development of blue-emitting colloidal Cu NCs through a novel and easy PEGylation method using different functional groups, including -SH and -COOH. The surface functionalization controls the size, cellular toxicity, and emission properties of Cu NCs. The combination of PEG, thiol, and carboxylic groups protects the particle surface from aggregation and oxidation. Among the samples, CAGP (Surface modified Cu NCs with -SH-COOH-PEG combination) emerges as an amazing candidate with the lowest toxicity and enhanced blue emission properties. The bright blue fluorescence emission from Hela cells after treatment with CAGP demonstrated this property. It also has excellent peroxide sensing potential, with a detection limit of 1.4 µM. Because of their excellent bioimaging and peroxide sensing properties, these Cu NCs could be a promising candidate for cellular oxidative stress sensing applications with high clinical relevance.

Using participatory action research to develop a new self-management program: Results from the design stage of Managing My MS My Way.

BACKGROUND: Self-management programs have been used with success in several clinical populations, and there is a growing body of evidence to support their use among persons with multiple sclerosis (MS). This group aimed to develop a novel self-management program, Managing My MS My Way (M4W), which is based in social cognitive theory and contains evidence-based strategies that have been shown to be effective for persons with MS. Furthermore, persons with MS would serve as stakeholders throughout the development process to ensure that the program would be useful and encourage adoption. This paper outlines the initial development stages of M4W, including determining 1) stakeholders' interest in a self-management program, 2) the general focus of the program, 3) the delivery method of the program, 4) the content of the program, and 5) potential barriers and adaptations. METHODS: A three-stage study consisting of an anonymous survey (n = 187) to determine interest, topic, and delivery format; semi-structured interviews (n = 6) to follow-up on the survey results; and semi-structured interviews (n = 10) to refine the content and identify barriers. RESULTS: Over 80% of survey participants were somewhat or very interested in a self-management program. Fatigue was the topic with the greatest amount of interest (64.7%). An internet-based program (e.g., mobile health or mHealth) was the most preferred delivery method (37.4%), with the first group of stakeholders proposing a module-based system with an initial in-person orientation session. The second group of stakeholders were overall enthusiastic about the program, giving moderate to high confidence scores for each of the proposed interventional strategies. Suggestions included skipping sections that were not applicable to them, setting reminders, and seeing their progress (e.g., visualizing their fatigue scores as they move through the program). In addition, stakeholders recommended larger font sizes and speech-to-text entry. CONCLUSIONS: Input from the stakeholders has been incorporated into the prototype of M4W. The next steps will be to test this prototype with another group of stakeholders to assess its initial usability and identify issues before developing the functional prototype.

Comparative effectiveness of TNF inhibitor vs IL-6 receptor inhibitor as monotherapy or combination therapy with methotrexate in biologic-experienced patients with rheumatoid arthritis: An analysis from the CorEvitas RA Registry.

OBJECTIVE: Randomized controlled trials (RCTs) in biologic-naïve rheumatoid arthritis (RA) patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 (IL-6) receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy. This observational study aimed to compare the effectiveness of TNFi vs IL-6Ri as mono- or combination therapy in biologic/targeted synthetic (b/ts) -experienced RA patients with moderate/high disease activity. METHODS: Eligible b/ts-experienced patients from the CorEvitas RA registry were categorized as TNFi and IL-6Ri initiators, with subgroups initiating as mono- or combination therapy. Mixed-effects regression models evaluated the impact of treatment on Clinical Disease Activity Index (CDAI), patient-reported outcomes, and disproportionate pain (DP). Unadjusted and covariate-adjusted effects were reported. RESULTS: Patients initiating IL-6Ri (n = 286) vs TNFi monotherapy (n = 737) were older, had a longer RA history and higher baseline CDAI, and were more likely to initiate as third-line therapy; IL-6Ri (n = 401) vs TNFi (n = 1315) combination therapy initiators had higher baseline CDAI and were more likely to initiate as third-line therapy. No significant differences were noted in the outcomes between TNFi and IL-6Ri initiators (as mono- or combination therapy). CONCLUSION: This observational study showed no significant differences in outcomes among b/ts-experienced TNFi vs IL-6Ri initiators, as either mono- or combination therapy. These findings were in contrast with the previous RCTs in biologic-naïve patients and could be explained by the differences in the patient characteristics included in this study. Further studies are needed to help understand the reasons for this discrepancy in the real-world b/ts-experienced population.