Ophthalmic Engineering (2nd Edition)

Infusion-related iatrogenic retinal breaks (IRBs) are a significant complication in vitrectomies, particularly when smaller-gauge cannulas are used during fluid infusion. Using two-dimensional finite element analysis (FEA), we analyzed forces exerted on the retina from different cannulas: traditional 25-gauge, 20-gauge, 23-gauge, and 27-gauge, then investigated four alternative new cannula designs: (A) oblique orifices, (B) external obstruction, (C) side ports, and (D) perpendicular orifices. The analysis revealed that the standard 25-gauge cannula had a force of 0.546 milli-Newtons (mN). Optimized cannulas demonstrated decreased forces: 0.072 mN (A), 0.266 mN (B), 0.417 mN (C), and 0.117 mN (D). While all the designs decrease fluid jet force, each has unique challenges: Design A may complicate manufacturing, B requires unique attachment techniques, C could misdirect fluid toward the lens and peripheral retina, and D requires a sealed trocar/cannula design to prevent unwanted fluid ejection. These four innovative cannula designs, identified with detailed engineering simulations, provide promising strategies to reduce the risk of IRBs during vitrectomy, bridging the gap between engineering insights and clinical application. Full article

Purpose: Previous studies have indicated an association between education and myopia, suggesting that numerous stress events during the educational process may influence eye health. This study aimed to investigate the impact of mental stress induced by mental arithmetic (MA) on choroidal thickness (CT). Methods: This study included 33 participants aged between 19 and 29 years. Swept-source optical coherence tomography (SS-OCT) was used to capture images of the posterior segment of the left eye during baseline and MA to assess changes in the CT. After denoising and compensation, the baseline images and MA images that had been rigidly registered and resampled to the baseline images were segmented using a deep learning-based method. Based on the segmentation results, the CT within the regions of 1 mm and 3 mm diameter centered at the lowest point of the fovea was calculated. Results: Significant increases were observed in both CT_1mm and CT_3mm during MA, with mean changes of 2.742 ± 7.098 μm (p = 0.034) and 3.326 ± 6.143 μm (p < 0.001), respectively. Conclusions: Thickening of the choroid has been observed during acute mental stress. We speculate that long-term or chronic mental stress could have a potential adverse impact on myopia progression. Full article

(1) Background: A rise in intraocular pressure (IOP) and decreased retinal ganglion cells are frequent indicators of effective modeling of chronic ocular hypertension in mice. In this study, the sensitivity of the mouse model to pharmaceutical therapy to reduce intraocular tension was assessed, the model’s safety was confirmed using a cytotoxicity test, and the success rate of the mouse model of ocular hypertension was assessed by assessing alterations in IOP and neurons in the ganglion cell layer. (2) Methods: A mouse model of chronic ocular hypertension was produced in this study by employing photocrosslinkable sericin hydrogel injection and LED lamp irradiation. The eyes of 25 C57BL/6 male mice were subjected to 405 nm UV light from the front for 2 min after being injected with 5 μL of sericin hydrogel in the anterior chamber of the left eye. IOP in the mice was measured daily, and IOP rises greater than 5 mmHg were considered intraocular hypertension. When the IOP was lowered, the intervention was repeated once, but the interval between treatments was at least 2 weeks. The right eyes were not treated with anything as a normal control group. Mice eyeballs were stained with HE, Ni-type, and immunofluorescence to assess the model’s efficacy. Two common drugs (tafluprost eye drops and timolol eye drops) were provided for one week after four weeks of stable IOP, and IOP changes were assessed to determine the drug sensitivity of the mouse model of chronic ocular hypertension. Furthermore, CellTiter 96^® AQueous One Solution Cell Proliferation Assay (MTS) was utilized to investigate the safety of the ocular hypertension model by evaluating the deleterious effects of photocrosslinkable sericin hydrogel on cells. (3) Results: Before injection, the basal IOP was (9.42 ± 1.28) mmHg (1 kPa = 7.5 mmHg) in the experimental group and (9.08 ± 1.21) in the control group. After injection, cataract occurred in one eye, corneal edema in one eye, endophthalmitis in one eye, iris incarceration in one eye, and eyeball atrophy in one eye. Five mice with complications were excluded from the experiment, and twenty mice were left. Four weeks after injection, the IOP of the experimental group was maintained at (19.7 ± 4.52) mmHg, and that of the control group was maintained at (9.92 ± 1.55) mmHg, and the difference between the two groups was statistically significant (p < 0.05). Before the intervention, the IOP in the experimental group was (21.7 ± 3.31) mmHg in the high IOP control group, (20.33 ± 2.00) mmHg in the tafluprost eye drops group, and (20.67 ± 3.12) mmHg in the timolol maleate eye drops group. The IOP after the intervention was (23.2 ± 1.03) mmHg, (12.7 ± 2.11) mmHg, and (10.4 ± 1.43) mmHg, respectively. Before and after the intervention, there were no significant differences in the high-IOP control group (p > 0.05), there were statistically significant differences in the timolol eye drops group (p < 0.05), and there were statistically significant differences in the tafluprost eye drops group (p < 0.05). One week after drug withdrawal, there was no significant difference in IOP among the three groups (p > 0.05). In the high-IOP group, the protein (sericin hydrogel) showed a short strips or fragmented structure in the anterior chamber, accompanied by a large number of macrophages and a small number of plasma cells. The shape of the chamber angle was normal in the blank control group. The number of retinal ganglion cells decreased significantly 8 weeks after injection of sericin hydrogel into the anterior chamber, and the difference was statistically significant compared with the blank control group (p < 0.05). After the cells were treated with photocrosslinkable sericin hydrogel, there was no significant difference in the data of the CellTiter 96^® assay kit of MTS compared with the blank control group (p > 0.05). (4) Conclusions: A mouse model of chronic intraocular hypertension can be established successfully by injecting sericin in the anterior chamber and irradiating with ultraviolet light. The model can simulate the structural and functional changes of glaucoma and can effectively reduce IOP after the action of most antihypertensive drugs, and it is highly sensitive to drugs. Sericin has no obvious toxic effect on cells and has high safety. Full article

Purpose: This study aimed to employ the incremental digital image correlation (DIC) method to obtain displacement and strain field data of the cornea from Corvis ST (CVS) sequences and access the performance of embedding these biomechanical data with machine learning models to distinguish forme fruste keratoconus (FFKC) from normal corneas. Methods: 100 subjects were categorized into normal (N = 50) and FFKC (N = 50) groups. Image sequences depicting the horizontal cross-section of the human cornea under air puff were captured using the Corvis ST tonometer. The high-speed evolution of full-field corneal displacement, strain, velocity, and strain rate was reconstructed utilizing the incremental DIC approach. Maximum (max-) and average (ave-) values of full-field displacement V, shear strain γxy, velocity VR, and shear strain rate γxyR were determined over time, generating eight evolution curves denoting max-V, max-γxy, max-VR, max-γxyR, ave-V, ave-γxy, ave-VR, and ave-γxyR, respectively. These evolution data were inputted into two machine learning (ML) models, specifically Naïve Bayes (NB) and Random Forest (RF) models, which were subsequently employed to construct a voting classifier. The performance of the models in diagnosing FFKC from normal corneas was compared to existing CVS parameters. Results: The Normal group and the FFKC group each included 50 eyes. The FFKC group did not differ from healthy controls for age (p = 0.26) and gender (p = 0.36) at baseline, but they had significantly lower bIOP (p < 0.001) and thinner central cornea thickness (CCT) (p < 0.001). The results demonstrated that the proposed voting ensemble model yielded the highest performance with an AUC of 1.00, followed by the RF model with an AUC of 0.99. Radius and A2 Time emerged as the best-performing CVS parameters with AUC values of 0.948 and 0.938, respectively. Nonetheless, no existing Corvis ST parameters outperformed the ML models. A progressive enhancement in performance of the ML models was observed with incremental time points during the corneal deformation. Conclusion: This study represents the first instance where displacement and strain data following incremental DIC analysis of Corvis ST images were integrated with machine learning models to effectively differentiate FFKC corneas from normal ones, achieving superior accuracy compared to existing CVS parameters. Considering biomechanical responses of the inner cornea and their temporal pattern changes may significantly improve the early detection of keratoconus. Full article

Background: To evaluate the corneal biomechanics of stable keratoconus suspects (Stable-KCS) at 1-year follow-up and compare them with those of subclinical keratoconus (SKC). Methods: This prospective case-control study included the eyes of 144 patients. Biomechanical and tomographic parameters were recorded (Corvis ST and Pentacam). Patients without clinical signs of keratoconus in both eyes but suspicious tomography findings were included in the Stable-KCS group (n = 72). Longitudinal follow-up was used to evaluate Stable-KCS changes. Unilateral keratoconus contralateral eyes with suspicious tomography were included in the SKC group (n = 72). T-tests and non-parametric tests were used for comparison. Multivariate general linear models were used to adjust for confounding factors for further analysis. Receiver operating characteristic (ROC) curves were used to analyze the distinguishability. Results: The biomechanical and tomographic parameters of Stable-KCS showed no progression during the follow-up time (13.19 ± 2.41 months, p > 0.05). Fifteen biomechanical parameters and the Stress–Strain Index (SSI) differed between the two groups (p < 0.016). The A1 dArc length showed the strongest distinguishing ability (area under the ROC = 0.888) between Stable-KCS and SKC, with 90.28% sensitivity and 77.78% specificity at the cut-off value of −0.0175. Conclusions: The A1 dArc length could distinguish between Stable-KCS and SKC, indicating the need to focus on changes in the A1 dArc length for keratoconus suspects during the follow-up period. Although both have abnormalities on tomography, the corneal biomechanics and SSI of Stable-KCS were stronger than those of SKC, which may explain the lack of progression of Stable-KCS. Full article

Keratoconus (KC), a leading cause of vision impairment, has an unclear aetiology. This study used Mendelian randomization (MR) to explore the causal links between various factors (smoking, asthma, Down syndrome, inflammatory bowel disease, atopic dermatitis, and serum 25-hydroxyvitamin D levels) and KC. A two-sample MR design, grounded in genome-wide association study (GWAS) summary statistics, was adopted using data from FinnGen, UK Biobank, and other GWAS-related articles. The inverse-variance weighted (IVW) method was employed, complemented by the Wald ratio method for factors with only one single-nucleotide polymorphism (SNP). Sensitivity and stability were assessed through Cochrane’s Q test, the MR-Egger intercept test, MR-PRESSO outlier test, and the leave-one-out analysis. The IVW results for the ORA (Ocular Response Analyzer) biomechanical parameters indicated significant associations between tobacco smoking (CH: p < 0.001; CRF: p = 0.009) and inflammatory bowel disease (CH: p = 0.032; CRF: p = 0.001) and corneal biomechanics. The Wald ratio method showed tobacco smoking was associated with a lower risk of KC (p = 0.024). Conversely, asthma (p = 0.009), atopic dermatitis (p = 0.012), inflammatory bowel disease (p = 0.017), and serum 25-hydroxyvitamin D levels (p = 0.039) were associated with a higher risk of KC by IVW, and the same applied to Down syndrome (p = 0.004) using the Wald ratio. These results underscore the role of corneal biomechanics as potential mediators in KC risk, warranting further investigation using Corvis ST and Brillouin microscopy. The findings emphasise the importance of timely screening for specific populations in KC prevention and management. Full article