Unveiling the gut-eye axis: how microbial metabolites influence ocular health and disease.

The intricate interplay between the gut microbiota and ocular health has surpassed conventional medical beliefs, fundamentally reshaping our understanding of organ interconnectivity. This review investigates into the intricate relationship between gut microbiota-derived metabolites and their consequential impact on ocular health and disease pathogenesis. By examining the role of specific metabolites, such as short-chain fatty acids (SCFAs) like butyrate and bile acids (BAs), herein we elucidate their significant contributions to ocular pathologies, thought-provoking the traditional belief of organ sterility, particularly in the field of ophthalmology. Highlighting the dynamic nature of the gut microbiota and its profound influence on ocular health, this review underlines the necessity of comprehending the complex workings of the gut-eye axis, an emerging field of science ready for further exploration and scrutiny. While acknowledging the therapeutic promise in manipulating the gut microbiome and its metabolites, the available literature advocates for a targeted, precise approach. Instead of broad interventions, it emphasizes the potential of exploiting specific microbiome-related metabolites as a focused strategy. This targeted approach compared to a precision tool rather than a broad-spectrum solution, aims to explore the therapeutic applications of microbiome-related metabolites in the context of various retinal diseases. By proposing a nuanced strategy targeted at specific microbial metabolites, this review suggests that addressing specific deficiencies or imbalances through microbiome-related metabolites might yield expedited and pronounced outcomes in systemic health, extending to the eye. This focused strategy holds the potential in bypassing the irregularity associated with manipulating microbes themselves, paving a more efficient pathway toward desired outcomes in optimizing gut health and its implications for retinal diseases.

Evaluating the Artificial Intelligence Performance Growth in Ophthalmic Knowledge.

OBJECTIVE: We aim to compare the capabilities of Chat Generative Pre-Trained Transformer (ChatGPT)-3.5 and ChatGPT-4.0 (OpenAI, San Francisco, CA, USA) in addressing multiple-choice ophthalmic case challenges. METHODS AND ANALYSIS: Both models' accuracy was compared across different ophthalmology subspecialties using multiple-choice ophthalmic clinical cases provided by the American Academy of Ophthalmology (AAO) "Diagnosis This" questions. Additional analysis was based on image content, question difficulty, character length of models' responses, and model's alignment with responses from human respondents. χ2 test, Fisher's exact test, Student's t-test, and one-way analysis of variance (ANOVA) were conducted where appropriate, with p<0.05 considered significant. RESULTS: GPT-4.0 significantly outperformed GPT-3.5 (75% versus 46%, p<0.01), with the most noticeable improvement in neuro-ophthalmology (100% versus 38%, p=0.03). While both models struggled with uveitis and refractive questions, GPT-4.0 excelled in other areas, such as pediatric questions (82%). In image-related questions, GPT-4.0 also displayed superior accuracy that trended toward significance (73% versus 46%, p=0.07). GPT-4.0 performed better with easier questions (93.8% (least difficult) versus 76.2% (middle) versus 53.3% (most), p=0.03) and generated more concise answers than GPT-3.5 (651.7±342.9 versus 1,112.9±328.8 characters, p<0.01). Moreover, GPT-4.0's answers were more in line with those of AAO respondents (57.3% versus 41.4%, p<0.01), showing a strong correlation between its accuracy and the proportion of AAO respondents who selected GPT-4.0's answer (ρ=0.713, p<0.01). CONCLUSION AND RELEVANCE: Our study demonstrated that GPT-4.0 significantly outperforms GPT-3.5 in addressing ophthalmic case challenges, especially in neuro-ophthalmology, with improved accuracy even in image-related questions. These findings underscore the potential of advancing artificial intelligence (AI) models in enhancing ophthalmic diagnostics and medical education.

Ophthalmology Faculty Diversity Trends in the US.

Importance: Enhancing the diversity of ophthalmologists can potentially contribute to diminishing disparities in eye care. Objectives: To investigate longitudinal trends in the representation of individuals underrepresented in medicine (URiM) and women among ophthalmology faculty compared with other specialties and to assess disparities between ophthalmology faculty demographic characteristics and the US population. Design, Setting, and Participants: In this cross-sectional study, a comprehensive analysis of Association of American Medical Colleges Faculty Roster data between 2000 and 2021 was conducted, using data from the US Medical School Faculty report on 56 438 ophthalmology faculty members. Main Outcomes and Measures: The data set was used to differentiate ophthalmology faculty members by gender, rank, and designation as a URiM individual. Outcome measures included changes in URiM and non-URiM faculty proportions, faculty rank, gender, department chair positions, and the US population between 2000 and 2021. Results: A total of 56 438 ophthalmology faculty members (37 511 men [66.5%]) were included in the study. The number of ophthalmology faculty increased from 1820 in 2000 to 3151 in 2021. Across all years, URiM female faculty represented 3.1% of ophthalmologists (1733 of 56 438), while URiM men accounted for 3.5% (1983 of 56 438). Overall, non-URiM men constituted 63.0% of ophthalmologists (35 528 of 56 438), and non-URiM women accounted for 30.5% (17 194 of 56 438). The proportion of URiM male faculty remained stable from 2000 to 2021 (63 of 1820 [3.5%] vs 104 of 3151 [3.3%]), with a small increase in URiM women faculty at junior faculty positions (2000, 40 of 1820 [2.2%]; 2021, 129 of 3151 [4.1%]; difference, 1.9% [95% CI, 0.9%-2.9%]). Proportions of non-URiM men decreased from 71.2% (1295 of 1820) in 2000 to 55.3% (1743 of 3151) in 2021 (difference, 15.8% [95% CI, 13.1%-18.6%]) and proportions of non-URiM women increased from 23.2% (422 of 1820) in 2000 to 37.3% (1175 of 3151) in 2021 (difference, 14.1% [95% CI, 11.5%-16.7%]). In terms of faculty rank, there were increases in representation of women from 2000 to 2021 at assistant professor (from 11.2% [203 of 1819] to 19.7% [622 of 3165]; difference, 8.5% [95% CI, 6.5%-10.5%]), associate professor (from 4.6% [83 of 1819] to 8.6% [271 of 3165]; difference, 4.0% [95% CI, 2.6%-5.4%]), and professor levels (from 2.8% [51 of 1819] to 7.1% [223 of 3165]; difference, 4.3% [95% CI, 3.9%-6.1%]). URiM representation remained stable at most ranks. Compared with other specialties, ophthalmology had among the lowest percentage change in URiM faculty. The expansion of ophthalmology's URiM faculty representation was less than one-third that of the diverse US population. Conclusion and Relevance: These findings highlight substantial growth in ophthalmology faculty and an increase in women's representation across several faculty ranks. However, URiM representation has remained largely unchanged, despite an increase at the associate professor level. This finding emphasizes the need for continued efforts to enhance diversity in academic ophthalmology.

Examining the Role of Telemedicine in Diabetic Retinopathy.

With the increasing prevalence of diabetic retinopathy (DR), screening is of the utmost importance to prevent vision loss for patients and reduce financial costs for the healthcare system. Unfortunately, it appears that the capacity of optometrists and ophthalmologists to adequately perform in-person screenings of DR will be insufficient within the coming years. Telemedicine offers the opportunity to expand access to screening while reducing the economic and temporal burden associated with current in-person protocols. The present literature review summarizes the latest developments in telemedicine for DR screening, considerations for stakeholders, barriers to implementation, and future directions in this area. As the role of telemedicine in DR screening continues to expand, further work will be necessary to continually optimize practices and improve long-term patient outcomes.

A Descriptive Analysis of Pediatric Ophthalmology Fellowship Program Directors.

There is limited literature on the characteristics of pediatric ophthalmology leadership. The authors examined the demographics, academic backgrounds, and scholarly output of pediatric ophthalmology fellowship program directors. Despite a positive trend in gender equity in this position, efforts remain to resolve the "leaky pipeline" of women into ophthalmology leadership. [J Pediatr Ophthalmol Strabismus. 2022;59(6):e69-e72.].

Highly enantioselective organocatalytic α-amination reactions of aryl oxindoles: developing designer multifunctional alkaloid catalysts.

An enantioselective α-amination of aryl oxindoles catalyzed by a dimeric quinidine has been developed. The reaction is general, broad in substrate scope, and affords the desired products in good yields with good to excellent enantioselectivities. This study provides the first examples of a general organocatalytic method for the creation of nitrogen-containing, tetrasubstituted chiral centers at C(3) of various aryl oxindoles. Furthermore, new catalysts and insights into structural elements of the catalysts that significantly influence enantioselectivities are disclosed.

Dimeric quinidine-catalyzed enantioselective aminooxygenation of oxindoles: an organocatalytic approach to 3-hydroxyoxindole derivatives.

3-Hydroxyoxindoles are common structural motifs found in a vast array of natural and biologically active molecules. Most catalytic methods for the asymmetric syntheses of these compounds require the use of transition-metal catalysts. In contrast, alternative catalytic procedures involving organocatalysis are scarce. Herein we disclose a novel aminooxygenation of oxindoles with nitrosobenzene catalyzed by a newly designed quinidine dimer to afford the desired products in good yields with enantioselectivities up to 96%. These reactions allow one to construct a C-O bond at the C(3) position of oxindoles with the creation of an oxygen-containing tetrasubstituted chiral center and provide a new, general organocatalytic approach to the synthesis of 3-hydroxyoxindole derivatives.

Expanding the scope of cinchona alkaloid-catalyzed enantioselective alpha-aminations of oxindoles: a versatile approach to optically active 3-amino-2-oxindole derivatives.

A cinchona alkaloid-catalyzed, highly enantioselective, alpha-amination of oxindoles has been developed. The reaction is general, operationally simple, and affords the desired products in high yields with good to excellent enantioselectivity. Significantly, this study provides a general catalytic method for the construction of a C-N bond at the C3 position of oxindoles as well as for the creation of a nitrogen-containing, tetrasubstituted chiral center.

Thiourea-catalyzed highly enantio- and diastereoselective additions of oxindoles to nitroolefins: application to the formal synthesis of (+)-physostigmine.

Oxindoles and their indoline derivatives are common structural motifs found in a wide array of natural and biologically active molecules. Most catalytic methods for the asymmetric syntheses of these compounds rely heavily on the use of transition-metal catalysts. In contrast, alternative catalytic procedures involving organocatalysis are scarce. Herein we disclose a conceptually novel organocatalytic approach to the syntheses of these materials using thiourea-catalyzed asymmetric 1,4-additions of oxindole derivatives to nitroolefins as a key step. These addition reactions create up to two stereogenic centers, one of which is a quaternary center. These reactions are broad in scope with respect to both the oxindole and nitroolefin substrates and provide the desired products in good yields with enantioselectivities of up to 99% and diastereoselectivities of up to >20:1. To demonstrate the utility of this approach, (+)-esermethole was synthesized in good overall yield over 3 steps starting from the 1,4-addition product, thereby providing a formal synthesis of (+)-physostigmine.

Mechanistic insights into the chiral phosphoramide-catalyzed, enantioselective crossed-aldol reactions of aldehydes.

[reaction: see text] The mechanism of the phosphoramide-catalyzed enantioselective aldol additions of trichlorosilyl enolate 1 to aldehydes has been studied. Natural abundance 12C/13C kinetic isotope analysis showed that the rate-determining step of the reaction is the aldolization. Arrhenius activation parameters for the aldol addition reaction were determined. The entropy of activation is large and highly negative, whereas the enthalpy of activation is relatively small. Despite the different trends in selectivity observed for electron-rich and electron-poor aldehydes, similar entropic and enthalpic contributions to the free energies of activation are found for both classes of substrates. The experimental results from the Arrhenius and the kinetic isotope effect studies allowed the formulation of an interpretation for the divergent selectivity trends in the aldol reaction.

Lewis base catalyzed enantioselective aldol addition of acetaldehyde-derived silyl enol ether to aldehydes.

[reaction: see text] Chiral phosphoramide catalyzed-enantioselective aldol addition of an acetaldehyde-derived trialkylsilyl enol ether to aromatic aldehydes provides protected aldol products in good yields with good to excellent enantioselectivities. Preliminary studies show that the aldolization intermediate (a chlorohydrin adduct) can be trapped with tert-butyl isocyanide to form an alpha-hydroxy lactone with good selectivity in a single-pot operation.

Chiral phosphoramide-catalyzed, enantioselective, directed cross-aldol reactions of aldehydes.

Catalytic, enantioselective, directed cross-aldol reactions of aldehydes are described. The addition of isobutyraldehyde trichlorosilyl enolate 2 to various aldehydes in the presence of 10 mol % bisphosphoramide 4 provides aldol products in high yields with moderate to good enantioselectivities. The reaction works well with a wide range of aromatic, olefinic, and aliphatic aldehydes. Enantioselectivities are highly dependent on the electronic nature of the aldehyde substituent. Hammett studies reveal that enantioselectivity increases as aldehydes become either more electron rich or more electron poor.