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Andrzej Grzybowski,1,2 Ronald A Schachar,3 Magdalena Gaca-Wysocka,2 Ira H Schachar,4 Barbara K Pierscionek5 1Institute for Research in Ophthalmology, Foundation for Ophthalmology Development, Poznan, 2Department of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland; 3Department of Physics, University of Texas, Arlington, TX, 4Byers Eye Institute of Stanford University, Palo Alto, CA, USA; 5School of Science and Technology, Nottingham Trent University, Nottingham, UK Purpose: To measure the maximum, objectively measured, accommodative amplitude, produced by pharmacologic stimulation.Methods: Thirty-seven healthy subjects were enrolled, with a mean age of 20.2±1.1 years, corrected visual acuity of 20/20, and mean spherical equivalent refraction (SER) =–0.83±1.60 diopters. For each subject, the right pupil was dilated with phenylephrine 10%. After 30 minutes, the pupil was measured, the left eye was patched, and the right eye was autorefracted. Pilocarpine 4% was then instilled in the right eye, followed by phenylephrine. At 45 minutes after the pilocarpine, autorefraction and pupil size were again measured.Results: Mean pupil size pre- and postpilocarpine was 8.0±0.8 mm and 4.4±1.9 mm, respectively. Pre- and postpilocarpine, the mean SER was –0.83±1.60 and –10.55±4.26 diopters, respectively. The mean pilocarpine-induced accommodative amplitude was 9.73±3.64 diopters. Five subjects had accommodative amplitudes ≥14.00 diopters. Accommodative amplitude was not significantly related to baseline SER (p-value =0.24), pre- or postpilocarpine pupil size (p-values =0.13 and 0.74), or change in pupil size (p-value =0.37). Iris color did not statistically significantly affect accommodative amplitude (p-value =0.83).Conclusion: Following topically applied pilocarpine, the induced objectively measured accommodation in the young eye is greater than or equal to the reported subjectively measured voluntary maximum accommodative amplitude. Keywords: maximum, accommodative amplitude, objective, pilocarpine

Abstract Background This study aimed to identify DNA methylation biomarkers associated with myopia using summary-data-based Mendelian randomization (SMR). Methods A systematic search of the PubMed, Web of Science, Cochrane Library, and Embase databases was conducted up to March 27, 2024. SMR analyses were performed to integrate genome-wide association study (GWAS) with methylation quantitative trait loci (mQTL) and expression quantitative trait loci (eQTL) studies. The heterogeneity in the dependent instrument (HEIDI) test was utilized to distinguish pleiotropic associations from linkage disequilibrium. Results The systematic review identified 26 DNA methylation biomarkers in five studies, with no overlap observed among those identified by different studies. After integrating GWAS with multi-omics data of mQTL and eQTL, six genes were significantly associated with myopia: PRMT6 (cg00944433 and cg15468180), SH3YL1 (cg03299269, cg11361895, and cg13354988), ZKSCAN4 (cg01192291), GATS (cg17830204), NPAT (cg04826772), and UBE2I (cg03545757 and cg08025960). Conclusions We identified six methylation biomarkers associated with the risk of myopia that may be helpful to elucidate the etiology mechanisms of myopia. Further experimental validation studies are required to corroborate these findings.

Background: Presbyopia, a common age-related condition affecting near vision, impacts over a billion people worldwide. The aim of this paper is to review the main reports and results of clinical trials, comparing the newest pharmacological treatment options for presbyopia, their mechanisms of action, and possible side effects. Main text: Pharmacological approaches, involving eye drops that target the underlying mechanisms of presbyopia, have gained growing interest. Two key pharmacological agents in this field are miotics and lens softeners. Miotics enhance near vision temporarily by creating a pinhole effect, though they may cause side effects and are under further investigation for long-term use with ongoing research also exploring the potential benefits of combining them with other drugs to improve outcomes and reduce adverse reactions. Lens softeners, on the other hand, aim to restore the flexibility of the lens, addressing one of the primary causes of presbyopia. Despite early trials, further development of lens softeners has been suspended. A notable advancement in this field is the recent FDA approval of 1.25% and 0.4% pilocarpine, a miotic agent, for presbyopia treatment. This milestone highlights the growing interest in pharmacological solutions for presbyopia, with several new drugs and their combinations currently being investigated for potential FDA approval. Conclusions: pharmacological treatments, particularly miotics like pilocarpine, represent a promising alternative to conventional methods for managing presbyopia. Continued research into these treatments, especially combinations of drugs, may offer more effective and convenient options for presbyopia patients in the future.

Andrzej Grzybowski,1,2 Bartosz L Sikorski,3 Francisco J Ascaso,4,5 Valentín Huerva6,7 1Department of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland; 2Department of Ophthalmology, Poznan City Hospital, Poznan, Poland; 3Department of Ophthalmology, Nicolaus Copernicus University, Bydgoszcz, Poland; 4Department of Ophthalmology, Hospital Clínico Universitario “Lozano Blesa”, Zaragoza, Spain; 5Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain; 6Department of Ophthalmology, Universitary Hospital Arnau de Vilanova, Lleida, Spain; 7IRB Lleida, Lleida, Spain Abstract: Pseudophakic cystoid macular edema (PCME) is the most common complication of cataract surgery, leading in some cases to a decrease in vision. Although the pathogenesis of PCME is not completely understood, the contribution of postsurgical inflammation is generally accepted. Consequently, anti-inflammatory medicines, including steroids and nonsteroidal anti-inflammatory drugs, have been postulated as having a role in both the prophylaxis and treatment of PCME. However, the lack of a uniformly accepted PCME definition, conflicting data on some risk factors, and the scarcity of studies comparing the role of nonsteroidal anti-inflammatory drugs to steroids in PCME prevention make the problem of PCME one of the puzzles of ophthalmology. This paper presents an updated review on the pathogenesis, risk factors, and use of anti-inflammatory drugs in PCME that reflect current research and practice. Keywords: Pseudophakic cystoid macular edema, cataract surgery, cataract surgery complications, retina, post-operative complications

Stephen G Schwartz,1 Andrzej Grzybowski,2 Harry W Flynn Jr1 1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Ophthalmology, Poznan City Hospital, Poznan, Poland Abstract: Endophthalmitis remains a rare but important cause of visual loss. Prophylaxis strategies are important to reduce rates of endophthalmitis after cataract surgery, intravitreal injection, and other procedures. There is substantial variability between the US and the rest of the world. During cataract surgery, intracameral antibiotics are commonly used in many nations, especially in Europe, but are less commonly used in the US. A randomized clinical trial from the European Society of Cataract and Refractive Surgeons reported an approximately fivefold reduction in endophthalmitis rates associated with intracameral cefuroxime but these results are controversial. There are no randomized clinical trials regarding endophthalmitis associated with intravitreal injection. Topical antibiotics are commonly used in many nations, but are less commonly used in the US. At this time, there is no global consensus and it appears unlikely that additional major clinical trials will conclusively define the optimal endophthalmitis prophylaxis techniques. Keywords: cataract surgery, endophthalmitis, intracameral antibiotic, intravitreal injection, prophylaxis

Abstract A large language model (LLM) is an artificial intelligence (AI) model that uses natural language processing (NLP) to understand, interpret, and generate human-like language responses from unstructured text input. Its real-time response capabilities and eloquent dialogue enhance the interactive user experience in human–AI communication like never before. By gathering several sources on the internet, LLM chatbots can interact and respond to a wide range of queries, including problem solving, text summarization, and creating informative notes. Since ophthalmology is one of the medical fields integrating image analysis, telemedicine, AI, and other technologies, LLMs are likely to play an important role in eye care in the near future. This review summarizes the performance and potential applicability of LLMs in ophthalmology according to currently available publications.

Background: The convergence of smartphone technology and artificial intelligence (AI) has revolutionized the landscape of ophthalmic care, offering unprecedented opportunities for diagnosis, monitoring, and management of ocular conditions. Nevertheless, there is a lack of systematic studies on discussing the integration of smartphone and AI in this field. Main text: This review includes 52 studies, and explores the integration of smartphones and AI in ophthalmology, delineating its collective impact on screening methodologies, disease detection, telemedicine initiatives, and patient management. The collective findings from the curated studies indicate promising performance of the smartphone-based AI screening for various ocular diseases which encompass major retinal diseases, glaucoma, cataract, visual impairment in children and ocular surface diseases. Moreover, the utilization of smartphone-based imaging modalities, coupled with AI algorithms, is able to provide timely, efficient and cost-effective screening for ocular pathologies. This modality can also facilitate patient self-monitoring, remote patient monitoring and enhancing accessibility to eye care services, particularly in underserved regions. Challenges involving data privacy, algorithm validation, regulatory frameworks and issues of trust are still need to be addressed. Furthermore, evaluation on real-world implementation is imperative as well, and real-world prospective studies are currently lacking. Conclusions: Smartphone ocular imaging merged with AI enables earlier, precise diagnoses, personalized treatments, and enhanced service accessibility in eye care. Collaboration is crucial to navigate ethical and data security challenges while responsibly leveraging these innovations, promising a potential revolution in care access and global eye health equity.

Abstract We conducted a systematic review of research in artificial intelligence (AI) for retinal fundus photographic images. We highlighted the use of various AI algorithms, including deep learning (DL) models, for application in ophthalmic and non-ophthalmic (i.e., systemic) disorders. We found that the use of AI algorithms for the interpretation of retinal images, compared to clinical data and physician experts, represents an innovative solution with demonstrated superior accuracy in identifying many ophthalmic (e.g., diabetic retinopathy (DR), age-related macular degeneration (AMD), optic nerve disorders), and non-ophthalmic disorders (e.g., dementia, cardiovascular disease). There has been a significant amount of clinical and imaging data for this research, leading to the potential incorporation of AI and DL for automated analysis. AI has the potential to transform healthcare by improving accuracy, speed, and workflow, lowering cost, increasing access, reducing mistakes, and transforming healthcare worker education and training.

George HH Beiko,1,2 Andrzej Grzybowski3,41Department of Surgery, McMaster University, Hamilton, ON, Canada; 2Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada; 3Department of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland, 4Department of Ophthalmology, Poznan City Hospital, Poznan, Poland We recently read the paper "Evaluation of in vitro glistening formation in hydrophobic acrylic intraocular lenses" by Thomes and Callaghan.1 The paper is extremely interesting in that the authors, employees of Alcon Research Ltd (Forth Worth, TX, USA), report not only that Alcon lenses have glistenings, but also that "continuous improvements on glistening formation"1 have been made by Alcon over the years from 2003 to 2012. We congratulate the authors and Alcon on their efforts, and on making this admission.The paper raises a number of concerns and questions. Firstly, the statement in the introduction, "Glistenings are typically observed within a few months of surgery and plateau approximately 1 year after surgical implantation of the [intraocular lens] IOL"1 is not referenced. The reported literature is in contradiction to this statement, in that the glistenings formation, as well as the severity of glistenings, has been reported to increase with longer follow-up times.2–8 Very few studies that evaluate the progression beyond one year find glistening formation to be stable.9–10 In addition, this statement is contradicted by the authors themselves in the introduction section of this paper where they state that a study by Colin et al4 found that 73.8% of the IOLs had glistenings when follow-up was less than 2 years, and 94.2% of the IOLs had glistenings when the follow-up was longer than 2 years. Even after10 years of follow-up, no plateau was seen.2View original paper by Thomes and Callaghan.

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Despite recent breakthroughs in understanding how protein sequence relates to structure and function, considerably less attention has been paid to the general features of protein surfaces beyond those regions involved in binding and catalysis. This article provides a systematic survey of the universe of protein surfaces and quantifies the sizes, shapes, and curvatures of the positively/negatively charged and hydrophobic/hydrophilic surface patches as well as correlations between such patches. It then compares these statistics with the metrics characterizing nanoparticles functionalized with ligands terminated with positively and negatively charged ligands. These particles are of particular interest because they are also surface patchy and have been shown to exhibit both antibiotic and anticancer activities—via selective interactions against various cellular structures—prompting loose analogies to proteins. The analyses support such analogies in several respects (e.g., patterns of charged protrusions and hydrophobic niches similar to those observed in proteins), although there are also significant differences. Looking forward, this work provides a blueprint for the rational design of synthetic nano‐objects with further enhanced mimicry of proteins’ surface properties.

We study how the Monte Carlo simulations of the critical dynamics of two-dimensional Ising lattices are affected by the quality (as compared to true randomness) of the pseudo-randomness used in them by computing an observable known to be sensitive to it: the dynamic critical exponent z. To this end, we first present a review of the literature and then perform the same simulations with different pseudo-randomness sources. We control the quality of the random streams by physically reseeding the generators and observe that while the mean value of the measured observable is slightly affected by the correlations within them, its variance does get a severe impact. By studying this affectation and how such pseudo-random streams perform under standard randomness tests based on statistical analysis, we conclude that the new protocol is able to detect other types of correlations and can thus be used as an additional test. On the other hand, we present the first (to the best of our knowledge) computation of the dynamic critical exponent with a perfectly random quantum random number generator (QRNG) and hypothesize that the presented strategy may point toward a route to establish quantum advantage based on the quality of results as complementary to those strategies based on the speed of the computational task.

Delays in autism spectrum disorder identification/services could impact developmental outcomes. Although trends are encouraging, children from historically underrepresented minority backgrounds are often identified later and have reduced engagement in care. It is unclear if disparities exist throughout the screen-evaluate-treat chain, or if early detection programs such as "Get SET Early" that standardize these steps are effective countermeasures. Pediatricians/primary care providers administered Communication and Symbolic Behavior Scales IT Checklist screens at 12-, 18-, and 24-month well-baby examinations, and parents designated race, ethnicity, and developmental concerns. Toddlers who scored in the range of concern, or whose pediatricians/primary care providers had concerns, were referred for evaluations. Rates of screening and evaluation engagement within ethnic/racial groups were compared to U.S. Census proportions. Age at screen, evaluation, and treatment and quantity was compared across groups. Regressions examined whether key factors were associated with ethnicity or race. No differences were found for mean age of screen, evaluation, initiation of behavioral therapy, or quantity received between racial and ethnic groups. Historically underrepresented minority children were more likely to fall into the range of concern, referred for evaluations, and have their parents express developmental concerns. Although there remain gaps within the pipeline, implementation of systemized programs can be effective in ensuring equitable access to resources across communities.