Faculty Bibliography

INTRODUCTION/BACKGROUND:Lifitegrast ophthalmic solution 5% is indicated to treat signs and symptoms of dry eye disease (DED). This study assessed eyecare professionals' (ECPs) real-world experiences with lifitegrast in DED. METHODS:A total of 12 ECPs (6 ophthalmologists and 6 optometrists) with experience prescribing lifitegrast completed a cross-sectional survey on practice characteristics, lifitegrast utilization, satisfaction, and adverse events (AEs). ECPs rated satisfaction with lifitegrast overall and for specific clinical outcomes versus other prescription eye drops on a 1 (very dissatisfied) to 10 (very satisfied) Likert scale. RESULTS:ECPs reported a mean of 1288 (range, 35-6000) patients with DED treated annually, with 20.9% receiving lifitegrast. Overall, 66.7% of ECPs reported near/complete symptom resolution in patients after 1-3 months of lifitegrast treatment. Mean (range) satisfaction ratings for onset/effectiveness were 6.8 (3-9)/6.6 (3-9). Satisfaction with reduction of DED signs was generally high: increased tear film breakup time, 5.8 (3-9); reduced conjunctival/corneal staining, 6.9 (3-9); increased Schirmer test score, 6.0 (3-9); increased tear meniscus height, 6.0 (3-9); and reduced Ocular Surface Disease Index severity, 7.0 (3-10). Symptom reduction satisfaction ratings were: itching, 5.3 (1-9); dryness, 6.9 (3-9); burning/stinging, 6.3 (1-9); redness, 6.2 (4-9); pain, 6.3 (3-9); light sensitivity, 6.5 (3-9); and blurred/poor vision, 6.8 (4-9). Overall satisfaction (ECPs/patients) was rated 7.1 (3-10)/6.8 (2-9). Predominant uses of lifitegrast included contact lens-induced DED (91.7%) and DED before/after refractive or cataract surgery (83.3% each). AEs reported were consistent with the known AE profile of lifitegrast and included burning/stinging, blurred vision, and dysgeusia. CONCLUSIONS:This real-world survey showed that ECPs use lifitegrast to treat one fifth of their patients with DED and reported moderate-to-high personal and patient satisfaction with lifitegrast treatment.

Allergic contact dermatitis (ACD) is a delayed-type IV hypersensitivity response driven by innate and adaptive immune cells. While specific immune regulations of these cell types are amply elucidated, their regulations by extracellular matrix (ECM) components and T cell mediated adaptive immunity in ACD remains unclear. Lumican and biglycan are ECM proteoglycans abundant in the dermis and lymph node, known to regulate innate immune myeloid cells, but have not been investigated in lymphoid cell regulations in ACD. By immunohistology we localized lumican and biglycan in skin biopsies of psoriatic patients. Using wild type (WT), lumican and biglycan knockout mice, we investigated CD4⁺T cell infiltration, activation and proliferation in the skin and draining lymph node (dLN) of CHS-challenged mice by immunohistochemistry and flow cytometry. We used the OT-II adoptive transfer model to test antigen specific CD4⁺T cell activation. We assessed interactions of the proteoglycans with LFA-1 on T cells by confocal microscopy. Compared to WTs, the knockouts showed severe ear inflammation, with increased CD4⁺T cells infiltration in the dermis. CHS-challenged knockout mice dLN showed increased T-bet, STAT1 and -STAT4 signaling, indicating enhanced Th1 commitment and proliferation. We found that WT lymph node fibroblastic reticular cells (FRCs) secrete lumican, biglycan and decorin, a related proteoglycan, while none are expressed by naive or activated T cells. Lumican and biglycan interact with LFA-1 on T cell surfaces, and in vitro all three proteoglycans suppress CD4⁺T cell activation. Secreted by dLN FRCs, lumican, biglycan, and possibly decorin interact with LFA-1 on CD4⁺T cells to restrict its activation and reduce dermatitis severity.

Fundus autofluorescence (FAF) imaging is a well-established retinal imaging technique that is widely used in the diagnostics of age-related macular degeneration (AMD). It facilitates the classification of distinct autofluorescence patterns, which may be predictive of AMD progression, the quantification of atrophic zones and their development over time and serves as a clinical endpoint in various studies. However, beyond autofluorescence intensity, emission spectra and fluorescence lifetime can be utilized to further investigate specific fluorophores, their changes in association with AMD, and their potential prognostic value in disease progression and therapy monitoring. In this review, we present the current state of spectrally and temporally resolved retinal FAF imaging in AMD. We explain the underlying principles, review the applied techniques, propose possible fluorophores contributing to FAF, summarize results from clinical studies as well as from histology and investigations in both in vivo and in vitro AMD models, and discuss the limitations of current techniques along with perspectives for technical development and clinical application.

BACKGROUND:Diversity, Equity, and Inclusion (DEI) initiatives aim to address systemic inequalities related to race, gender, socioeconomic status, and other identities in workplaces and society. Rooted in the civil rights struggles of the United States, DEI has evolved from affirmative action policies of the 1960s to broader efforts promoting inclusive environments and equitable opportunities. OBJECTIVES/OBJECTIVE:This paper explores the core principles of DEI, its historical context in American legal discrimination, the evolution and expansion of DEI initiatives, evidence-based responses to common criticisms, and the ongoing challenges and societal benefits of advancing DEI efforts. METHODS:A comprehensive literature review of historical documents, legislative milestones, social movements, contemporary literature was conducted to synthesize the evolution and practical implications of DEI. This approach facilitates a nuanced understanding of DEI's necessity and impact within health equity. RESULTS:DEI encompasses diversity (valuing differences), equity (fair treatment and access), and inclusion (empowering participation). Historical legal discrimination against African Americans, including slavery, Black Codes, Jim Crow laws, and voter suppression, created deep-seated systemic inequities within American society, workplaces, and healthcare. Affirmative action, initiated in the 1960s, laid the foundation for modern DEI efforts, which have expanded to include multiple marginalized groups. DEI initiatives have benefits to individuals and organizations that improve collaborate and innovation to overall enhance U.S. population health and wellbeing. CONCLUSIONS:DEI remains a vital framework for addressing historical and systemic inequalities in American society and workplaces, particularly within healthcare. Effective DEI programs require sustained commitment, expert facilitation, and broad-based support to overcome resistance. Continued advocacy and research are essential to realize the full benefits of DEI for all individuals and organizations.

PURPOSE/OBJECTIVE:To investigate the presence of hypertransmission (HT) in normal aging, early (e)AMD, and intermediate (i)AMD, changes over 3 years, and the impact of HTs ≥ 250 µm (LHyperTD) on seven tests of scotopic, mesopic, and photopic vision. DESIGN/METHODS:Prospective cohort study. SUBJECTS/METHODS:Participants of the Alabama Study on Early Age-Related Macular Degeneration 2. METHODS:ALSTAR2 participants underwent spectral domain optical coherence tomography angiography (OCTA), color fundus photography, and vision testing at baseline and 3-year follow-up. HT presence and stepped diameters in choroidal en face slabs were assessed with custom review software. Only LHyperTD were analyzed at follow-up. AMD was staged via AREDS 9-step. Vision at baseline and follow-up between eyes with and without LHyperTD was analyzed with linear regression. MAIN OUTCOME MEASURES/METHODS:Presence, size, and illustrative examples of HT, association with tests of photopic, mesopic and scotopic vision. RESULTS:Baseline data was available on 460 eyes of 460 patients (mean age 71.5 ± 5.7 years, 277 female; 236 normal, 134 eAMD, 90 iAMD). HT of any size were found in iAMD (86.7%), eAMD (35.1%), and normal (3.8%) eyes, with proportional LHyperTD (13.3% vs 4.2% vs 0.4%, p < 0.01). For 339 eyes (mean age 71.2 ± 5.8 years, 206 female, 181 normal, 92 eAMD, 66 iAMD), LHyperTD presence significantly increased in normal (p = 0.01) and iAMD (p < 0.01) but not in eAMD eyes. At baseline, photopic contrast sensitivity (CS), mesopic CS, and rod intercept time (for rod mediated dark adaptation, RMDA) were worse in eyes with LHyperTD compared to eyes without (all p < 0.01). At follow-up, the same were worse in LHyperTD (all p < 0.01), as well as low luminance visual acuity (p < 0.01) and scotopic light sensitivity (p = 0.05). CONCLUSION/CONCLUSIONS:LHyperTD are rare in normal and eAMD eyes and associate with mesopic and scotopic visual functions in addition to risk-indicating RMDA. Delayed RMDA reflects other factors other than LHyperTD including differences in disease stage. Our analysis of HT < 250 µm may inform other studies of early disease. LHyperTD are best utilized as imaging biomarkers for later stages of iAMD than ALSTAR2.

What makes human brains distinctive? The answer is hidden at least partially in the myriad synaptic connections made between neurons - the connectome. The foveal retina is a primate specialization which presents a feasible site for deriving a complete connectome of a human CNS structure. In the fovea, cells and circuits are miniaturized and compressed to densely sample the visual image at highest resolution and initiate form, color and motion perception. Here we provide a draft connectome of all neurons in a human fovea. We found synaptic connections, distinct to humans, linking short-wavelength sensitive cones to color vision pathways. Moreover, by reconstructing excitatory synaptic pathways arising from cone photoreceptors we found that over 95% of foveal ganglion cells contribute to only three major pathways to the brain. Our study reveals unique features of a human neural system and opens a door to a complete foveal connectome.

PURPOSE/OBJECTIVE:To describe the multimodal imaging findings of the angular sign of Henle fiber layer (HFL) hyperreflectivity (ASHH) at baseline and follow-up in patients with contusion maculopathy. METHODS:Eleven eyes of ten patients were captured with multimodal imaging after non-penetrating ocular blunt trauma from a soccer ball, fist, or airsoft pellet. Baseline clinical and imaging characteristics and follow-up outcomes are presented. RESULTS:Hyper-reflective lesions extending along the HFL from the ellipsoid zone (EZ) to the outer plexiform layer consistent with ASHH were identified with optical coherence tomography (OCT). Mean presenting visual acuity (VA) was logMAR 0.59 ± 0.64 (Snellen VA 20/77, range 20/25 to counting fingers) and follow-up visual acuity was logMAR 0.43 ± 0.35 (Snellen VA 20/53, range 20/20 to 20/200). Additional OCT findings included external limiting membrane attenuation and retinal pigment epithelium (RPE) disruption. On follow-up, resolution of ASHH was accompanied by outer nuclear layer thinning with varying degrees of EZ attenuation and RPE loss. A macular hole was detected in one patient on follow-up. CONCLUSION/CONCLUSIONS:ASHH is a distinctive acute OCT feature of contusion maculopathy secondary to blunt injury, causing disruption of the photoreceptors and presumably anterograde alterations in the HFL. Associated RPE alterations may ensue, either acutely or delayed, and are a biomarker of persistent structural abnormalities and variable visual outcomes.

PURPOSE/OBJECTIVE:To identify areas of consensus among global experts for the management of Fuchs endothelial corneal dystrophy (FECD) in clinical practice, including its diagnosis, evaluation, decision-making principles with respect to intervention, and recommendations for performing cataract surgery in patients with FECD, including when to combine with keratoplasty. DESIGN/METHODS:Modified Delphi-based global consensus. PARTICIPANTS/METHODS:Thirty-seven ophthalmologists from around the world with significant expertise in the management and mechanisms of FECD. METHODS:A series of consensus statements about FECD were developed from three iterative rounds of structured questions and statements posed to the panel of experts. Two rounds were asynchronous electronic questionnaires, and the third round was a live virtual meeting. Experts responded anonymously to statements assessing consensus and to open-ended questions that invited diverse input. MAIN OUTCOME MEASURES/METHODS:Consensus was defined as ³70% agreement among experts. RESULTS:Consensus was reached for 90 of 91 statements after three rounds. Experts agreed that FECD is defined by the presence of central or paracentral scattered or confluent guttae with or without edema. There was strong consensus that a chronic state of subclinical edema precedes the onset of clinically detectable edema that may or may not cause symptoms. With near-unanimous consensus, disease evaluation recommendations included assessing for findings that implicate the cornea as a source of decreased vision to separate it from the effect of comorbid conditions, as this would inform whether corneal intervention is appropriate. These findings include diurnal variation in vision, clinical or subclinical (tomographic) edema, and changes or differences in central corneal thickness. Based on current evidence, experts agreed that there are no effective medical therapies for FECD, and that Descemet membrane endothelial keratoplasty is the surgical treatment of choice when indicated. CONCLUSIONS:The consensus statements provide current globally endorsed recommendations for the diagnosis and management of FECD. The guidelines are important and relevant for general ophthalmologists, who typically first diagnose and evaluate FECD, and for cornea specialists, by allowing them to benchmark their current practice patterns against expert recommendations. This could help improve patient outcomes and establish a framework adaptable to future advances and evolving technologies in the management of FECD.

What makes human brains distinctive? The answer is hidden at least partially in the myriad synaptic connections made between neurons - the connectome. The foveal retina is a primate specialization which presents a feasible site for deriving a complete connectome of a human CNS structure. In the fovea, cells and circuits are miniaturized and compressed to densely sample the visual image at highest resolution and initiate form, color and motion perception. Here we provide a draft connectome of all neurons in a human fovea. We found synaptic connections, distinct to humans, linking short-wavelength sensitive cones to color vision pathways. Moreover, by reconstructing excitatory synaptic pathways arising from cone photoreceptors we found that over 95% of foveal ganglion cells contribute to only three major pathways to the brain. Our study reveals unique features of a human neural system and opens a door to a complete foveal connectome.

PURPOSE/UNASSIGNED:To allow exploration of xanthophyll carotenoids in vision and age-related macular degeneration progression using two-wavelength autofluorescence imaging for macular pigment optical density (MPOD), we developed tools for automatically centering and classifying the MPOD distribution pattern. METHODS/UNASSIGNED:A subset of the ALSTAR2 baseline cohort (NCT04112667) and 44 eyes of adults aged 20 to 30 years with healthy maculas were imaged with optical coherence tomography and two-wavelength autofluorescence (MPOD module, Heidelberg Engineering). Images underwent a quality review. Two custom FIJI plugins centered the MPOD distribution by five algorithms (FOVEA, HILLCLIMB, CENTROID, MAX, CONTOUR). Others automatically classified spatial distributions into four patterns from Obana et al: Peak, Ring, Mixed, and Dip. RESULTS/UNASSIGNED:Of 651 qualifying aged eyes and 44 young eyes, the HILLCLIMB and CONTOUR methods best agreed with a manually determined foveal center. Regarding spatial distribution pattern, 445 aged eyes (68.4%) showed peaks, 118 (18.1%) rings, 41 (6.3%) mixed, and 47 (7.2%) dips. In young eyes, 40 (90%) showed peaks, 1 (2.3%) rings, 3 (6.8%) mixed, and none showed dips. Notably, peaks were significantly (P < 0.001) more prominent in men (74.1%) than women (65.0%) and pseudophakic (72.7%) than phakic (62.9%) eyes. CONCLUSIONS/UNASSIGNED:Automatic tools for MPOD centration are reliable and robust. Future studies will use the HILLCLIMB and CONTOUR algorithms. TRANSLATIONAL RELEVANCE/UNASSIGNED:Automated MPOD pattern assignment suggests that the spatial distribution of MPOD varies with gender, lens status, and possibly age. Our analytic software can be applied to large samples for studies of xanthophyll carotenoid impact on vision and age-related macular degeneration progression.