A 3D-Printed and Freely Available Device to Measure the Zebrafish Optokinetic Response Before and After Injury.

Zebrafish eyes are anatomically similar to humans and have a higher percentage of cone photoreceptors more akin to humans than most rodent models, making them a beneficial model organism for studying vision. However, zebrafish are different in that they can regenerate their optic nerve after injury, which most other animals cannot. Vision in zebrafish and many other vertebrate animals, including humans, can be accessed using the optokinetic response (OKR), which is an innate eye movement that occurs when tracking an object. Because fish cannot use an eye chart, we utilize the OKR that is present in virtually all vertebrates to determine if a zebrafish has vision. To this end, we have developed an inexpensive OKR setup that uses 3D-printed and off-the-shelf parts. This setup has been designed and used by undergraduate researchers and is also scalable to a classroom laboratory setup. We demonstrate that this setup is fully functional for assessing the OKR, and we use it to illustrate the return of the OKR following optic nerve injury in adult zebrafish.

Differential Impact of 0.01% and 0.05% Atropine Eyedrops on Ocular Surface in Young Adults.

Purpose: To evaluate the effect of low-concentration (0.01% and 0.05%) atropine eyedrops on ocular surface characteristics in young adults. Methods: Twenty-six myopic students aged 18 to 30 years were randomly assigned to receive either 0.01% or 0.05% atropine once nightly for 14 days, followed by cessation, with a ≥14-day interval between each administration. Assessments were conducted one, two, seven, and 14 days after using atropine with corresponding timepoints after atropine cessation. Tear meniscus height and first and average noninvasive keratograph tear film breakup time (NIKBUT-first, NIKBUT-average) were measured using Keratograph 5M, whereas the objective scatter index (OSI) was measured by OQAS II devices; the ocular surface disease index (OSDI) score was also obtained. Results: The mean OSI peaked after two days of administration of 0.05% atropine (ß = 0.51, P = 0.001), accompanied by significant decreases in NIKBUT-first (ß = -7.73, P < 0.001) and NIKBUT-average (ß = -8.10, P < 0.001); the OSDI peaked after 14 days (ß = 15.41, P < 0.001). The above parameters returned to baseline one week after atropine discontinuation (all P > 0.05). NIKBUT-first and NIKBUT-average reached their lowest points after 14 days of 0.01% atropine administration (NIKBUT-first: ß = -4.46, P = 0.005; NIKBUT-average: ß = -4.42, P = 0.001), but those significant changes were diminished once atropine treatment stopped. Conclusions: Young adult myopes experienced a significant but temporary impact on the ocular surface with 0.05% atropine administration, whereas 0.01% atropine had a minimal effect. Translational Relevance: The investigation of the ocular surface effects of different concentrations of atropine may inform evidence-based clinical decisions regarding myopia control in young adults.

Does the introduction of streamlight decrease refractive surgery operating time?

PURPOSE: The aim of the study was to analyze the time-savings associated with introduction of Streamlight™ (Alcon Laboratories, Fort Worth, TX, USA) transepithelial photorefractive keratectomy (PRK) in surface corneal ablations. METHODS: All refractive surgeries were performed using the Alcon WaveLight® EX500 at the ArtLife Clinic, Gdansk, Poland. The study included patients treated for refractive errors with transepithelial PRK between April 2019 and October 2021, who were matched with patients treated with alcohol-assisted PRK during the same period. Only results for the left eye were analyzed. RESULTS: One-hundred-five patients underwent transepithelial PRK (age 33.42 ± 8.67 years) and were matched with 105 patients that underwent alcohol-assisted PRK (age 33.05 ± 10.16 years; p = 0.11). The mean preoperative spherical equivalent refraction was - 2.04 ± 2.28 D, and - 1.9 ± 1.71 D for the transepithelial and alcohol-assisted PRK group, respectively (p = 0.20). The total surgery time was non-significantly shorter in transepithelial PRK (349.46 ± 47.83 s) than in alcohol-assisted PRK (354.93 ± 137.63 s; p = 0.7); however, the variance of surgical time was significantly lower in transepithelial PRK (p < 0.001). The laser treatment duration was greater in transepithelial PRK (41.78 ± 17.2 s) than in alcohol-assisted PRK (8.48 ± 6.12 s; p < 0.001), and so was the number of breaks during the laser treatment (0.95 ± 0.63 vs. 0.53 ± 0.88, respectively; p < 0.001). CONCLUSION: The introduction of transepithelial PRK did not bring significant time-associated savings into the refractive surgery suite.

Janus kinase-signal transducer and activator of transcription signaling pathway in the ocular cells of rat fetuses exposed to maternal saturated fat ingestion.

OBJECTIVE: The aim of this study was to analyze possible alterations (morphological and inflammatory) in the ocular cells of fetuses from mothers with insulin resistance exposed to saturated fatty acids through the period of pregnancy. METHODS: Wistar female rats were induced to develop insulin resistance before pregnancy. Fetuses' skulls were collected on the 20th day of intrauterine life. The rats were separated on the first day of management into two groups according to the diet applied: control group (C): diet containing soybean oil as a source of fat; and saturated fatty acid group (S): diet containing butter as a source of fat. RESULTS: Histological and immunohistochemical analyses have been conducted. The immunohistochemical analyses of interleukin 6, suppressor of cytokine signaling, 3 and signal transducer and activator of transcription 3 did not demonstrate alterations in the expression of proteins in the fetuses of mothers fed with a saturated fatty diet. Moreover, no histopathological changes were noticed between groups. CONCLUSION: The saturated fatty diet does not induce tissue changes or activate the Janus kinase/signal transducer and activator of transcription signaling pathway during eye development in the fetuses of mothers with insulin resistance.

The protective effect of vitamin A palmitate eye gel on the ocular surface during general anaesthesia surgery: a randomized controlled trial.

PURPOSE: To investigate the change in tear production associated with general anesthesia and the protective effect of vitamin A palmitate eye gel on the ocular surface during general anesthesia. METHODS: This double-blind, randomized clinical trial included patients undergoing non-ophthalmic surgery under general anesthesia who randomly received vitamin A palmitate eye gel and taping for one eye (Group A, n = 60) or taping alone for the other eye (Group B, n = 60). Symptom assessment in dry eye (SANDE) score, tear film break-up time (TBUT), corneal fluorescein staining (CFS) score, and Schirmer tear test I (STT-1) were analyzed under a hand-held slit lamp before anesthesia (T0), 0.5 h postoperatively (T1), and 24 h postoperatively (T2). RESULTS: At 0.5 h postoperatively, an increase in CFS score was observed in both groups (P < 0.05 in Group A and P < 0.01 in Group B), and the participants in Group A had less corneal abrasions than those in Group B. STT-1 significantly increased in Group A (P < 0.05), while it significantly decreased in Group B (P < 0.001). The changes between the two groups were statistically significant (P < 0.001). At 24 h postoperatively, both CFS score and STT-1 almost returned to baseline levels in the two groups. In both groups, the SANDE score and TBUT showed little change at 0.5 h and 24 h postoperatively (all P > 0.05). CONCLUSION: Vitamin A palmitate eye gel effectively protected the ocular surface and aqueous supplementation during general anesthesia. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100052140) on 20/10/2021.

Short-term results of surgical treatment in large idiopathic macular hole cases.

PURPOSE: To evaluate results of the surgical treatment for large stage (Stage 3 and 4) idiopathic macular hole cases with and without ILM flap technique. METHODS: Sixty eyes of 60 patients diagnosed with idiopathic macular hole (MH) were included in the study. Complete ophthalmologic examination and SD-OCT examination were performed in all eyes. MH stages, MH base diameter, height and closest distance were measured quantitatively. Postoperative and 3 months visits were evaluated. RESULTS: The mean age of the cases was 65.0 ± 8.0 (range 30-84) years, there were 31 (51.7%) female and 29 (48.3%) male patients with a mean follow-up period of 18.1 ± 16.7 (range 3-63) months. The mean best corrected visual acuity recorded at preoperative and third month control visits were 0.89 ± 0.40(preoperative) logMAR, 0.82 ± 0.60(3 month) logMAR (p < 0.05). The mean MH index was 0.48 ± 0.16, the closest hole distance was 517.86 ± 210.89 µm and mean basal diameter of holes was 947.78 ± 361.90 µm and the average height was 448.93 ± 79.80 microns. There was no statistically significant difference between anatomic results of macular hole surgery with (n = 22) and without (n = 38) flap in terms of hole closure (86.4% vs. 92.1% p > 0.05). In 90% (54 cases) of the cases, closure was observed after the first surgery. Two eyes that failed macular hole surgery were reoperated. In one of these eyes, anatomical success was obtained with macular hole massage and mechanical cytumulation. However, anatomical success could not be achieved in the other eye. CONCLUSiON: In the treatment of large macular holes, pars plana vitrectomy, internal limiting membrane peeling with/without flap and gas tamponade demonstrated high anatomical and functional success.

Can (Natural) deep eutectic systems increase the efficacy of ocular therapeutics?

The eye is one of the most complex organs in the human body, with a unique anatomy and physiology, being divided into anterior and posterior segments. Ocular diseases can occur in both segments, but different diseases affect different segments. Glaucoma and cataracts affect the anterior segment, while macular degeneration and diabetic retinopathy occur in the posterior segment. The easiest approach to treat ocular diseases, especially in the anterior segment, is through the administration of topical eye drops, but this route presents many constraints, namely precorneal dynamic and static ocular barriers. On the other hand, the delivery of drugs to the posterior segment of the eye is far more challenging and is mainly performed by the intravitreal route. However, it can lead to severe complications such as retinal detachment, endophthalmitis, increased intraocular pressure and haemorrhage. The design of new drug delivery systems for the anterior segment is very challenging, but targeting the posterior one is even more difficult and little progress has been made. In this review we will discuss various strategies including the incorporation of additives in the formulations, such as viscosity, permeability, and solubility enhancers, namely based on Deep eutectic systems (DES). Natural deep eutectic systems (NADES) have emerged to solve several problems encountered in pharmaceutical industry, regarding the pharmacokinetic and pharmacodynamic properties of drugs. NADES can contribute to the design of advanced technologies for ocular therapeutics, including hydrogels and nanomaterials. Here in, we revise some applications of (NA)DES in the development of new drug delivery systems that can be translated into the ophthalmology field.

External Disruption of Ocular Development in Utero.

The intricate steps of human ocular embryology are impacted by cellular and genetic signaling pathways and a myriad of external elements that can affect pregnancy, such as environmental, metabolic, hormonal factors, medications, and intrauterine infections. This review focuses on presenting some of these factors to recognize the multifactorial nature of ocular development and highlight their clinical significance. This review is based on English-language articles sourced from PubMed, Web of Science, and Google Scholar; keywords searched included "ocular development in pregnancy," "ocular embryology," "maternal nutrition," "ophthalmic change," and "visual system development." While some animal models show the disruption of ocular embryology from these external factors, there are limited post-birth assessments in human studies. Much remains unknown about the precise mechanisms of how these external factors can disrupt normal ocular development in utero, and more significant research is needed to understand the pathophysiology of these disruptive effects further. Findings in this review emphasize the importance of additional research in understanding the dynamic association between factors impacting gestation and neonatal ocular development, particularly in the setting of limited resources.

Influence of corneal astigmatism on near and far vision in eyes with bifocal intraocular lenses.

Here, we present a full wave propagation model that quantitatively assesses the effect of astigmatism on visual functions in eyes with diffractive bifocal IOLs. The proposed model with bifocal IOLs evaluated the image quality of each focus at varying degrees of corneal astigmatism with the metrics of modulation transfer function and light-in-the-bucket. The results show that corneal astigmatism alters the distance-near image quality balance. Positive (negative) astigmatism has more detrimental effects on far (near) vision. Additionally, bifocal IOLs are more vulnerable to corneal astigmatism, highlighting the need to consider multifocal toric IOLs with astigmatism greater than 1.0 D. The numerical results closely agreed with previous relevant clinical findings, suggesting the clinical usability of the presented method in predicting the postoperative visual function of patients.

Closed head injury combined with orbital blowout fracture and displacement of the eyeball into the maxillary sinus in a 14-year-old boy: a case report.

BACKGROUND: Trauma-induced orbital blowout fracture (OBF) with eyeball displacement into the maxillary sinus is rare. CASE PRESENTATION: We present the case of a 14-year-old with a closed head injury, OBF, and displacement of the eyeball into the maxillary sinus following a car accident. A prompt transconjunctival access surgery was performed for eyeball repositioning and orbital reconstruction in a single session, mitigating anaesthesia-related risks associated with multiple surgeries. At the 12-month follow-up, his visual acuity was 20/200. Despite limited eye movement and optic nerve atrophy, overall satisfaction with the ocular appearance was achieved. CONCLUSIONS: This report offers novel insights into the mechanisms of OBF occurrence and the development of postoperative complications.

Ocular dominance-dependent binocular combination of monocular neuronal responses in macaque V1.

Primates rely on two eyes to perceive depth, while maintaining stable vision when either one eye or both eyes are open. Although psychophysical and modeling studies have investigated how monocular signals are combined to form binocular vision, the underlying neuronal mechanisms, particularly in V1 where most neurons exhibit binocularity with varying eye preferences, remain poorly understood. Here, we used two-photon calcium imaging to compare the monocular and binocular responses of thousands of simultaneously recorded V1 superficial-layer neurons in three awake macaques. During monocular stimulation, neurons preferring the stimulated eye exhibited significantly stronger responses compared to those preferring both eyes. However, during binocular stimulation, the responses of neurons preferring either eye were suppressed on the average, while those preferring both eyes were enhanced, resulting in similar neuronal responses irrespective of their eye preferences, and an overall response level similar to that with monocular viewing. A neuronally realistic model of binocular combination, which incorporates ocular dominance-dependent divisive interocular inhibition and binocular summation, is proposed to account for these findings.

Code-Free Machine Learning Approach for EVO-ICL Vault Prediction: A Retrospective Two-Center Study.

Purpose: Establishing a development environment for machine learning is difficult for medical researchers because learning to code is a major barrier. This study aimed to improve the accuracy of a postoperative vault value prediction model for implantable collamer lens (ICL) sizing using machine learning without coding experience. Methods: We used Orange data mining, a recently developed open-source, code-free machine learning tool. This study included eye-pair data from 294 patients from the B&VIIT Eye Center and 26 patients from Kim's Eye Hospital. The model was developed using OCULUS Pentacam data from the B&VIIT Eye Center and was internally evaluated through 10-fold cross-validation. External validation was performed using data from Kim's Eye Hospital. Results: The machine learning model was successfully trained using the data collected without coding. The random forest showed mean absolute errors of 124.8 µm and 152.4 µm for the internal 10-fold cross-validation and the external validation, respectively. For high vault prediction (>750 µm), the random forest showed areas under the curve of 0.725 and 0.760 for the internal and external validation datasets, respectively. The developed model performed better than the classic statistical regression models and the Google no-code platform. Conclusions: Applying a no-code machine learning tool to our ICL implantation datasets showed a more accurate prediction of the postoperative vault than the classic regression and Google no-code models. Translational Relevance: Because of significant bias in measurements and surgery between clinics, the no-code development of a customized machine learning nomogram will improve the accuracy of ICL implantation.

Peripheral Refraction Using Ancillary Retinoscope Component (P-ARC).

Purpose: To assess the agreement of retinoscope-based peripheral refraction techniques with the criterion standard open-field autorefractor. Methods: Fifty young adults (mean age, 24 ± 3 years) participated in this study. Two masked, experienced senior examiners carried out central refraction and peripheral refraction at the temporal 22° (T22°) and nasal 22° (N22°) eccentricities. Peripheral refraction techniques were (a) peripheral refraction using ancillary retinoscope component (P-ARC), (b) retinoscopy with eye rotation, and (c) open-field autorefractor. Peripheral refraction with retinoscopy values was compared with an open-field autorefractor (Shinn Nippon NVision-K) to assess the agreement. All measurements were taken from the right eye under noncycloplegic conditions. Results: The mean difference ±95% limits of agreement of peripheral refraction values obtained using P-ARC from T22° (+0.11 diopters [D] ± 1.20 D; P = 0.20) or N22° (+0.13 D ± 1.16 D; P = 0.13) were comparable with open-field autorefractor. The eye rotation technique compared to autorefractor showed a significant difference for T22° (+0.30 D ± 1.26 D; P = 0.002); however, there was an agreement for N22° (+0.14 D ± 1.16 D; P = 0.10). With respect to the identification of peripheral refraction patterns, examiners were able to identify relative peripheral hyperopia in most of the participants (77%). Conclusions: Peripheral refraction with P-ARC was comparable with open-field autorefractor at T22° and N22° eccentricities. Peripheral retinoscopy techniques can be another approache for estimating and identifying peripheral refraction and its patterns in a regular clinical setting. Translational Relevance: Retinoscope with P-ARC has high potential to guide and enable eye care practitioners to perform peripheral refraction and identify peripheral refraction patterns for effective myopia management.

Motion-Defined Form Perception in Deprivation Amblyopia.

Purpose: The purpose of this study was to assess motion-defined form perception, including the association with clinical and sensory factors that may drive performance, in each eye of children with deprivation amblyopia due to unilateral cataract. Methods: Coherence thresholds for orientation discrimination of motion-defined form were measured using a staircase procedure in 30 children with deprivation amblyopia and 59 age-matched controls. Visual acuity, stereoacuity, fusion, and interocular suppression were also measured. Fixation stability and fellow-eye global motion thresholds were measured in a subset of children. Results: Motion-defined form coherence thresholds were elevated in 90% of children with deprivation amblyopia when viewing with the amblyopic eye and in 40% when viewing with the fellow eye. The deficit was similar in children with a cataract that had been visually significant at birth (congenital) and in children for whom the cataract appeared later in infancy or childhood (developmental). Poorer motion-defined form perception in amblyopic eyes was associated with poorer visual acuity, poorer binocular function, greater interocular suppression, and the presence of nystagmus. Fellow-eye deficits were not associated with any of these factors, but a temporo-nasal asymmetry for global motion perception in favor of nasalward motion suggested a general disruption in motion perception. Conclusions: Deficits in motion-defined form perception are common in children with deprivation amblyopia and may reflect a problem in motion processing that relies on binocular mechanisms.

Disease-Causing TIMP3 Variants and Deep Phenotyping of Two Czech Families with Sorsby Fundus Dystrophy Associated with Novel p.(Tyr152Cys) Mutation.

We aim to report the ocular phenotype and molecular genetic findings in two Czech families with Sorsby fundus dystrophy and to review all the reported TIMP3 pathogenic variants. Two probands with Sorsby fundus dystrophy and three first-degree relatives underwent ocular examination and retinal imaging, including optical coherence tomography angiography. The DNA of the first proband was screened using a targeted ocular gene panel, while, in the second proband, direct sequencing of the TIMP3 coding region was performed. Sanger sequencing was also used for segregation analysis within the families. All the previously reported TIMP3 variants were reviewed using the American College of Medical Genetics and the Association for Molecular Pathology interpretation framework. A novel heterozygous variant, c.455A>G p.(Tyr152Cys), in TIMP3 was identified in both families and potentially de novo in one. Optical coherence tomography angiography documented in one patient the development of a choroidal neovascular membrane at 54 years. Including this study, 23 heterozygous variants in TIMP3 have been reported as disease-causing. Application of gene-specific criteria denoted eleven variants as pathogenic, eleven as likely pathogenic, and one as a variant of unknown significance. Our study expands the spectrum of TIMP3 pathogenic variants and highlights the importance of optical coherence tomography angiography for early detection of choroidal neovascular membranes.

A Clinical, Pharmacological, and Formulation Evaluation of Melatonin in the Treatment of Ocular Disorders-A Systematic Review.

Melatonin's cytoprotective properties may have therapeutic implications in treating ocular diseases like glaucoma and age-related macular degeneration. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. This study aims to summarize the screened articles on melatonin's clinical, pharmacological, and formulation evaluation in treating ocular disorders. The identification of relevant studies on the topic in focus was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. The studies were searched in the following databases and web search engines: Pubmed, Scopus, Science Direct, Web of Science, Reaxys, Google Scholar, Google Patents, Espacenet, and Patentscope. The search time interval was 2013-2023, with the following keywords: melatonin AND ocular OR ophthalmic AND formulation OR insert AND disease. Our key conclusion was that using melatonin-loaded nano-delivery systems enabled the improved permeation of the molecule into intraocular tissues and assured controlled release profiles. Although preclinical studies have demonstrated the efficacy of developed formulations, a considerable gap has been observed in the clinical translation of the results. To overcome this failure, revising the preclinical experimental phase might be useful by selecting endpoints close to clinical ones.

Fuchs' uveitis syndrome: a 20-year experience in 466 patients.

Fuchs Uveitis Syndrome (FUS), also known as Fuchs Heterochromic Iridocyclitis, is a chronic form of uveitis characterized by mild inflammation primarily affecting one eye. This study aimed to investigate the clinical and epidemiological features of FUS in an Iranian population. A retrospective analysis was conducted on 466 patients diagnosed with FUS at an ophthalmology center affiliated with Isfahan University of Medical Sciences between 2003 and 2021. The Kimura et al. criteria were used for FUS diagnosis. Demographic data, clinical characteristics, misdiagnosed cases, concurrent diseases, and associated ocular findings were analyzed. The study included 507 eyes of 466 FUS patients, with a mean age of 34.01 ± 11.25 years. Iris atrophy, keratic precipitates, and vitritis were common clinical findings. Heterochromia was an infrequent feature. Initial misdiagnosis occurred in 13 patients, with pars planitis being the most common incorrect diagnosis. Toxoplasmosis and multiple sclerosis were common concurrent diseases. Pediatric FUS cases were noted, possibly attributed to early-onset manifestations. Differences in clinical characteristics were observed when compared to other populations. This study provides insights into the clinical and epidemiological aspects of FUS in an Iranian population. Variations in clinical features, misdiagnosis patterns, and concurrent diseases were noted. Attention to specific clinical parameters can aid in accurate FUS diagnosis. Understanding these differences contributes to a better understanding of FUS presentation and its relationship with other diseases.

Visualization of Cataract Surgery Steps With 4D Microscope-Integrated Swept-Source Optical Coherence Tomography in Ex Vivo Porcine Eyes.

Purpose: To investigate the visualization capabilities of high-speed swept-source optical coherence tomography (SS-OCT) in cataract surgery. Methods: Cataract surgery was simulated in wet labs with ex vivo porcine eyes. Each phase of the surgery was visualized with a novel surgical microscope-integrated SS-OCT with a variable imaging speed of over 1 million A-scans per second. It was designed to provide four-dimensional (4D) live-volumetric videos, live B-scans, and volume capture scans. Results: Four-dimensional videos, B-scans, and volume capture scans of corneal incision, ophthalmic viscosurgical device injection, capsulorrhexis, phacoemulsification, intraocular lens (IOL) injection, and position of unfolded IOL in the capsular bag were recorded. The flexibility of the SS-OCT system allowed us to tailor the scanning parameters to meet the specific demands of dynamic surgical steps and static pauses. The entire length of the eye was recorded in a single scan, and unfolding of the IOL was visualized dynamically. Conclusions: The presented novel visualization method for fast ophthalmic surgical microscope-integrated intraoperative OCT imaging in cataract surgery allowed the visualization of all major steps of the procedure by achieving large imaging depths covering the entire eye and high acquisition speeds enabling live volumetric 4D-OCT imaging. This promising technology may become an integral part of routine and advanced robotic-assisted cataract surgery in the future. Translational Relevance: We demonstrate the visualization capabilities of a cutting edge swept-source OCT system integrated into an ophthalmic surgical microscope during cataract surgery.