A rare case of acantholytic squamous cell carcinoma presenting on non-sun exposed palpebral conjunctiva.

Purpose: This report describes the clinical and histological characteristics and management of a keratinized lesion of the palpebral conjunctiva in a 59-year-old male. The lesion was identified as a rare acantholytic variant of squamous cell carcinoma that atypically arose from a non-sun exposed region of palpebral conjunctiva. Management was complete excision via Mohs surgery. Observations: A 59-year-old male presented with ocular irritation and chronic foreign body sensation in the right eye. Exam revealed a keratinized lesion in the right lower tarsal conjunctiva, and an initial shave biopsy was non-diagnostic. 12 months later, the patient presented with similar symptoms and a larger, more irregular lesion for which histopathology of a tarsal-involving excisional biopsy was consistent with acantholytic squamous cell carcinoma with involved margins. The patient subsequently underwent complete excision via Mohs surgery and a secondary reconstruction. Conclusions and importance: Acantholytic variants of squamous cell carcinoma are rare and are described as arising from areas with routine sun exposure. This case reports such a lesion arising from non-sun exposed tarsal conjunctiva, as identified by histopathology of a full-thickness excisional biopsy. The lesion was successfully managed with complete excision via Mohs surgery and secondary reconstruction. Given that this histologic variant may be more aggressive and have higher rates of recurrence than other forms of squamous cell carcinoma, this case highlights the importance of complete excisional biopsy and accurate histopathology of concerning periocular lesions and offers a template for management of similar lesions. The unique presenting location should bring awareness to consideration of this type of malignancy developing on palpebral conjunctiva.

Reversible Chemical Modification of Antibody Effector Function Mitigates Unwanted Systemic Immune Activation.

Antibody effector functions including antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) are mediated through the interaction of the antibody Fc region with Fcγ receptors present on immune cells. Several approaches have been used to modulate antibody Fc-Fcγ interactions with the goal of driving an effective antitumor immune response, including Fc point mutations and glycan modifications. However, robust antibody-Fcγ engagement and immune cell binding of Fc-enhanced antibodies in the periphery can lead to the unwanted induction of systemic cytokine release and other dose-limiting infusion-related reactions. Creating a balance between effective engagement of Fcγ receptors that can induce antitumor activity without incurring systemic immune activation is an ongoing challenge in the field of antibody and immuno-oncology therapeutics. Herein, we describe a method for the reversible chemical modulation of antibody-Fcγ interactions using simple poly(ethylene glycol) (PEG) linkers conjugated to antibody interchain disulfides with maleimide attachments. This method enables dosing of a therapeutic with muted Fcγ engagement that is restored in vivo in a time-dependent manner. The technology was applied to an effector function enhanced agonist CD40 antibody, SEA-CD40, and experiments demonstrate significant reductions in Fc-induced immune activation in vitro and in mice and nonhuman primates despite showing retained efficacy and improved pharmacokinetics compared to the parent antibody. We foresee that this simple, modular system can be rapidly applied to antibodies that suffer from systemic immune activation due to peripheral FcγR binding immediately upon infusion.

Comparison of Standard 7-Field, Clarus, and Optos Ultrawidefield Imaging Systems for Diabetic Retinopathy (COCO Study).

Purpose: The purpose of this study was to compare diabetic retinopathy (DR) severity levels assessed from 7 standard-field stereoscopic color photographs on a 35° fundus camera to both Clarus and Optos ultrawidefield color images. Design: Cross-sectional, comparative imaging study. Participants: Participants with DR imaged at a single-center retina practice. Methods: Participants were imaged on 3 cameras at a single visit with the Topcon 35° fundus camera, Clarus, and Optos. The DR Severity Scale (DRSS) level was determined within the 7-field (7F) area of each image set using the ETDRS scale. An additional global DRSS was assigned for both Clarus and Optos images using the entire visible retina. Weighted kappa (wκ) measured the agreement between cameras. Main Outcome Measures: The primary outcome was a 3-way comparison of DRSS level within the 7F area imaged on the 3 cameras. Secondary outcomes included a comparison of the DRSS obtained with standard 7F imaging to the global DRSS of Clarus and Optos and a comparison of the global DRSS between Clarus and Optos only. Results: Ninety-seven eyes (50 participants) were evaluated. Agreement within 1-step of ETDRS levels between standard 7F imaging and Clarus 7F was 90.1% (wκ = 0.65), and with Optos 7F in 85.9%, (wκ = 0.58). Agreement within 1-step between standard 7F imaging and Clarus global was 88.9% of eyes (wκ = 0.63), and Optos global was 85.7%, (wκ = 0.54). Agreement between Clarus and Optos global DR level within 1-step was 89.1% (wκ = 0.68). Intergrader agreement for the 7F ETDRS level was 96% for standard 7F imaging, 98% for Clarus, and 95.5% for Optos. Conclusions: These findings suggest that when evaluating the 7F area on Clarus and Optos, DR severity grades are comparable to standard 7F imaging. However, it is important to understand the unique attributes and differences of each fundus camera when changing the type of system used in a clinical setting due to upgrading equipment. Additionally, if the facility has access to > 1 device, there should not be an exchange between cameras for the same patient. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Biometric Indicators for Maximizing Intermediate Vision with a Monofocal IOL.

Purpose: To determine refractive or biometric variables that might be predictive of increased intermediate vision in patients receiving an Eyhance monofocal intraocular lens (IOL). Methods: This prospective, single-center, bilateral, non-randomized, open-label, observational study included a total of 110 subjects (220 eyes). Subjects had been previously bilaterally implanted with an Eyhance monofocal IOL (Johnson & Johnson Vision Care, Inc.) and were later divided into 2 groups based on their postoperative visual acuity. Subjects that had binocular distance corrected intermediate visual acuity (DCIVA) of 0.2 logMAR or better were classified into the Enhanced Group, and the remaining subjects were classified into the Non-Enhanced Group. Refractive outcomes and biometric measurements were compared between groups. Results: The number of subjects in each group was 61 for the Enhanced Group, and 49 for the Non-Enhanced Group. There were significant differences in pupil size between groups, with pupil sizes in the Enhanced Group significantly smaller than in the Non-Enhanced Group (p < 0.01). Subjects also reported significantly more dysphotopsias in the Non-Enhanced Group compared to the Enhanced Group (p = 0.03). Multiple regression analysis identified pupil size and axial length as significant predictors of increased monocular intermediate vision. Conclusion: The results of this study suggest that pupil size could be a predictor of increased intermediate vision in a patient receiving an Eyhance monofocal IOL.

Head-to-Head Comparison of Intermediate Vision of Two Monofocal Intraocular Lenses.

Purpose: To compare intermediate visual outcomes in patients previously implanted with bilateral Clareon monofocal IOLs versus bilateral Eyhance IOLs. Methods: This was a non-interventional, single-center, examiner-masked, comparative study. Participants were cataract patients presenting at least 3 months after uncomplicated, bilateral implantation of either Clareon or Eyhance non-toric and toric IOLs. Outcomes measures included binocular distance-corrected intermediate visual acuity (DCIVA), binocular corrected distance visual acuity (CDVA), binocular best-corrected defocus curve, postoperative mean residual spherical equivalent (MRSE), and residual astigmatism. Results: A total of 620 eyes of 310 subjects (155 subjects per group) were evaluated. The mean difference in DCIVA was 0.05 logMAR between the Eyhance and Clareon IOLs which was significant (p < 0.01), but within the 0.1 logMAR non-inferiority margin. Mean CDVA of the Clareon group was 0.01 ± 0.03 logMAR compared to 0.02 ± 0.03 logMAR of the Eyhance Group (p > 0.05). Defocus curves from +1.0 D to -3.0 D were not clinically nor statistically different between the Clareon and Eyhance groups (p > 0.05). Conclusion: The results of this study show that bilateral implantation of Clareon monofocal IOLs and Eyhance monofocal IOLs lead to similar distance and intermediate visual outcomes.

Modified adaptation of the twist-and-out technique for intraocular lens exchange.

Many methods can be used to explant an intraocular lens (IOL) after prior cataract surgery. Here, we describe a modified approach to the twist-and-out technique for IOL removal. The IOL is dissected and brought into the anterior chamber (AC), where 1 haptic is externalized. The adaptation in this technique occurs next; an additional paracentesis is made 180 degrees away from an adjacent side port, and the shaft of a 25-gauge cannula is threaded across the AC to connect these incisions. This maneuver frees both hands to use forceps within the incision, grasp the IOL, and rotate it around the forceps. The use of both hands allows for a smaller, more controlled movement than the original 1-handed pronation. The cannula shaft aids in twisting the IOL tightly around the forceps while protecting the corneal endothelium. The forceps-lens complex is then withdrawn, extracting the IOL whole with 1 efficient movement.

Resident physicians using modern practices for excellent documentation and care in heart failure (PUMPED CHF).

The most common indication for readmission among Medicare patients is congestive heart failure (CHF). Prior studies underscore the use of residents to bolster hospital-wide programs and reduce CHF readmissions. The authors assessed the effectiveness of a novel online training program designed to improve resident documentation and knowledge related to CHF. The findings suggest that despite a significant increase in knowledge scores following the online educational course, there was only a slight increase in documentation scores. Additional teaching modalities need to be identified to foster resident education and create sustained behavior change.

Effects of nonlinear frequency compression on speech identification in children with hearing loss.

OBJECTIVES: This study evaluated effects of nonlinear frequency compression (NLFC) processing in children with hearing loss for consonant identification in quiet and for spondee identification in competing noise or speech. It was predicted that participants would benefit from NLFC for consonant identification in quiet when access to high-frequency information was critical, but that NLFC would be less beneficial, or even detrimental, when identification relied on mid-frequency cues. Further, it was hypothesized that NLFC could result in greater susceptibility to masking in the spondee task. The rationale for these predictions is that improved access to high-frequency information comes at the cost of decreased spectral resolution. DESIGN: A repeated-measures design compared speech-perception outcomes in 17 pediatric hearing aid users (9 to 17 years of age) wearing Naida V SP "laboratory" hearing aids with NLFC on and off. Data were also collected in an initial baseline session in which children wore their personal hearing aids. Children with a wide range of audiometric configurations were included, but all participants were full-time users of hearing aids with active NLFC. For each hearing aid condition, speech perception was assessed in the sound field by using a closed-set 12-alternative consonant-vowel identification measure in quiet, and a closed-set four-alternative spondee-identification measure in a speech-shaped noise or in a two-talker speech masker. RESULTS: No significant differences in performance were observed between laboratory hearing aid conditions with NLFC activated or deactivated for either speech-perception measure. An unexpected finding was that the majority of participants had no difficulty identifying the high-frequency consonant /s/ even when NLFC was deactivated. Investigation into individual differences revealed that subjects with a greater difference in audible bandwidth with NLFC on versus NLFC off were less likely to demonstrate improvements in high-frequency consonant identification in quiet, but were more likely to demonstrate improvements in spondee identification in speech-shaped noise. Group results observed in the initial baseline assessment using personal aids fitted with more aggressive NLFC settings than used in laboratory aids indicated better consonant identification accuracy in quiet. However, spondee identification in the two-talker masker was poorer with personal compared with laboratory hearing aids. Comparisons across personal and laboratory hearing aids are tempered, however, by the potential of an order effect. CONCLUSIONS: The observation of comparable performance with NLFC on and NLFC off in the laboratory aids provides evidence that NLFC is neither detrimental nor advantageous when modest in strength. Results with personal hearing aids fitted with stronger compression settings than laboratory aids (NLFC on) highlight the critical need for further research to determine the impact of NLFC processing on speech perception for a wider range of speech-perception measures and compression settings.

Influence of hearing loss on children's identification of spondee words in a speech-shaped noise or a two-talker masker.

OBJECTIVE: This study evaluated the influence of hearing loss on children's speech-perception abilities in a speech-shaped noise or a two-talker masker. For both masker conditions, it was predicted that children with hearing loss would require a more advantageous signal to noise ratio (SNR) than children with normal hearing to achieve the same criterion level of performance. However, it was hypothesized that the performance gap between children with hearing loss and children with normal hearing would be larger in the two-talker than in the speech-shaped noise masker. DESIGN: A repeated-measures design compared the spondee identification performance of two age groups of children with hearing loss (9-11 and 13-17 years of age) and a group of children with normal hearing (9-11 years of age) in continuous speech-shaped noise or a two-talker masker. Estimates of the SNR required for 70.7% correct spondee identification were obtained using an adaptive, four-alternative, forced-choice procedure. Children were tested in the sound field. Children with hearing loss wore their personal hearing aids at their regular settings during testing. RESULTS: Both groups of children with hearing loss performed more poorly than children with normal hearing in the speech-shaped noise masker. Younger children required an additional 2.7 dB SNR and older children required an additional 4.7 dB SNR to achieve the same level of performance as children with normal hearing. This disadvantage decreased to 8.1 dB for both age groups of children with hearing loss in the two-talker masker. For children with hearing loss, degree of hearing loss was significantly correlated with performance in the speech-shaped noise masker, but not in the two-talker masker. CONCLUSIONS: A larger performance gap was observed between children with hearing loss and children with normal hearing in competing speech than in steady state noise. These results are consistent with the hypothesis that hearing loss influenced children's perceptual processing abilities.