Objective To investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment.Methods Established patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response. ResultsAlthough healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases.Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination. ConclusionsIn two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.

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The fluid-ventilated, gas-permeable scleral lens is an important front-line tool for managing many corneal disorders refractory to other treatment measures or otherwise requiring keratoplasty.

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As the biological alarm of impending or actual tissue damage, pain is essential for our survival. However, when it is initiated and/or sustained by dysfunctional elements in the nociceptive system, it is itself a disease known as neuropathic pain. While the critical nociceptive system provides a number of protective functions, it is unique in its central role of monitoring, preserving and restoring the optical tear film in the face of evaporative attrition without which our vision would be non-functional. Meeting this existential need resulted in the evolution of the highly complex, powerful and sensitive dry eye alarm system integrated in the peripheral and central trigeminal sensory network. The clinical consequences of corneal damage to these nociceptive pathways are determined by the type and location of its pathological elements and can range from the spectrum known as dry eye disease to the centalised oculofacial neuropathic pain syndrome characterised by a striking disparity between the high intensity of symptoms and paucity of external signs. These changes parallel those observed in somatic neuropathic pain. When seen through the neuroscience lens, diseases responsible for inadequately explained chronic eye pain (including those described as dry eye) can take on new meanings that may clarify long-standing enigmas and point to new approaches for developing preventive, symptomatic and disease-modifying interventions for these currently refractory disorders.

Objective To evaluate the relationships of quantitative and semi-quantitative (SQ) assessments of synovium with knee OA severity by radiographic and 3T MRI findings. Methods 58 knee OA patients underwent non-fluoroscopic fixed-flexion knee radiographs. Dynamic contrast-enhanced (CE) 3T MRI was performed pre-/post-gadolinium administration to quantify synovial volume (qSV). SQ synovial outcomes were assessed on CE and unenhanced images. Two radiologists scored X-rays using the OARSI atlas; inter-reader agreement was assessed using Kappas and concordance correlation coefficients. Multiple linear and logistic regression analysis was used to assess associations among variables while controlling the effects of age, BMI, gender and meniscal extrusion. Results KL grade, diseased compartment joint space width (dcJSW) and diseased compartment joint space narrowing (dcJSN) were significantly associated with synovial proliferation, measured as CE qSV (β = 0.78, p = 0.0001; β = -0.22, p = 0.0003; β = 0.53, p = 0.0001, respectively). Furthermore, qSV strongly correlated with total subchondral BML volume (β = 0.22, p = 0.0003). KL grade, dcJSW, and dcJSN were significantly associated with BLOKS SQ infrapatellar synovitis (OR [95%CI]: 9.05, [1.94,42.3]; 0.75 [0.54,1.03]; 2.22 [1.15,4.31], respectively) and effusion (OR [95%CI]: 5.75, [1.23,26.8]; 0.70, [0.50,0.98]; 1.96, [1.02,3.74], respectively). CE SQ synovitis also significantly associated with KL and dcJSN (β = 0.036, p = 0.0040; β = 0.015, p=0.0266, respectively), and BLOKS synovitis. Conclusion Synovitis is a characteristic feature of advancing knee OA stages, and is significantly associated with KL, JSW, JSN, and BMLs. BLOKS synovitis scoring on unenhanced MRI is associated with CE synovitis measures.

Purpose To investigate the feasibility of correcting ocular higher order aberrations (HOA) in keratoconus (KC) using wavefront-guided optics in a scleral lens prosthetic device (SLPD). Methods Six advanced keratoconus patients (11 eyes) were fitted with a SLPD with conventional spherical optics. A custom-made Shack-Hartmann wavefront sensor was used to measure aberrations through a dilated pupil wearing the SLPD. The position of SLPD, i.e. horizontal and vertical decentration relative to the pupil and rotation were measured and incorporated into the design of the wavefront-guided optics for the customized SLPD. A submicron-precision lathe created the designed irregular profile on the front surface of the device. The residual aberrations of the same eyes wearing the SLPD with wavefront-guided optics were subsequently measured. Visual performance with natural mesopic pupil was compared between SLPDs having conventional spherical and wavefront-guided optics by measuring best-corrected high-contrast visual acuity and contrast sensitivity. Results Root-mean-square of HOA(RMS) in the 11 eyes wearing conventional SLPD with spherical optics was 1.17±0.57μm for a 6 mm pupil. HOA were effectively corrected by the customized SLPD with wavefront-guided optics and RMS was reduced 3.1 times on average to 0.37±0.19μm for the same pupil. This correction resulted in significant improvement of 1.9 lines in mean visual acuity (p<0.05). Contrast sensitivity was also significantly improved by a factor of 2.4, 1.8 and 1.4 on average for 4, 8 and 12 cycles/degree, respectively (p<0.05 for all frequencies). Although the residual aberration was comparable to that of normal eyes, the average visual acuity in logMAR with the customized SLPD was 0.21, substantially worse than normal acuity. Conclusions The customized SLPD with wavefront-guided optics corrected the HOA of advanced KC patients to normal levels and improved their vision significantly.