1.Modeling and finite element analysis of human trabecular meshwork outflow pathways.
Shiya BAO ; Qing SUN ; Si CHEN ; Xinyu CHEN ; Xiang PENG ; Jing ZHANG
Journal of Biomedical Engineering 2025;42(3):585-591
Glaucoma is the leading cause of irreversible blindness worldwide, with its primary risk factor arising from elevated intraocular pressure (IOP) due to an imbalance between aqueous humor production and outflow. This study aims to establish quantitative correlations among IOP, iris mechanical properties, channel microstructures, and aqueous humor dynamics through three-dimensional modeling and finite element analysis, overcoming the limitations of conventional experimental techniques in studying aqueous flow within the trabecular meshwork (TM) outflow pathway. A three-dimensional fluid-structure interaction (FSI) model incorporating the layered TM structure, Schlemm's canal (SC), iris, and other anterior segment tissues was developed based on human ocular anatomy. FSI simulations were performed to quantify the effects of IOP variations and iris Young's modulus on tissue morphology and aqueous humor dynamics parameters. The computational results demonstrated that axial iris deformation showed significant correlations with IOP and iris Young's modulus. Although elevated IOP exhibited minimal effects on hydrodynamic parameters in the anterior and posterior chambers, it markedly suppressed aqueous flow velocity in the TM region. Additionally, wall shear stress in SC and collector channels displayed high sensitivity to IOP variations. These findings reveal that the tissue mechanics-FSI mechanism modulates outflow resistance by regulating aqueous humor dynamics, offering valuable references for developing clinical therapies targeting IOP reduction in glaucoma management.
Humans
;
Trabecular Meshwork/anatomy & histology*
;
Finite Element Analysis
;
Aqueous Humor/metabolism*
;
Intraocular Pressure/physiology*
;
Glaucoma/physiopathology*
;
Iris/anatomy & histology*
;
Computer Simulation
;
Models, Biological
2.Clinical profile of Keratoconus patients at the Philippine General Hospital
Pablito F. Sandoval Jr. Sandoval Jr. ; George Michael N. Sosuan ; Reginald Robert G. Tan ; Ruben Lim Bon Siong
Philippine Journal of Ophthalmology 2024;49(1):33-38
Objectives:
This study described the clinical profile of patients with keratoconus at a single tertiary referral hospital.
Methods:
This was a single-center, retrospective, cross-sectional study that reviewed medical records of
patients diagnosed with keratoconus from January 2015 to August 2022. Data on the clinical profile,
intervention, and clinical outcomes were collected from the chart review.
Results:
Forty (40) patients (79 eyes) were included in the study. Majority (98%) had bilateral disease in which
22 (55.5%) were affected asymmetrically. The mean age was 21 years. Most patients (72.5%) were male. Blurring
of vision was the chief complaint in all patients. Atopy was present in 23 patients (57.5%). History of vigorous
eye rubbing was present in 31 (77.5%). The mean interval from onset of symptoms to consult was 46.4 ± 33.38
months. The mean pinhole corrected distance visual acuity was 0.47 ± 0.41 (Snellen equivalent of 20/59). The
average spherical equivalent was -7.48D ± 6.99D. Corneal protrusion on slit-lamp biomicroscopy was seen in
78 eyes (98.7%). Other findings included Fleischer ring (53.2%), Vogt's striae (19.0%), and apical corneal scar
(24.0%). Only one eye (1.3%) had no corneal findings. Thirty-nine eyes (49.3%) were classified as advancedsevere keratoconus. Rigid contact lens was planned for 60 eyes (75.9%). Sixty-two eyes (78.5%) were for
collagen cross-linking. Deep anterior lamellar keratoplasty was planned in 10 eyes (12.7%) and penetrating
keratoplasty in two eyes (2.5%).
Conclusion
Keratoconus at the Philippine General Hospital was most frequently seen in young males and
asymmetrically affects both eyes. Patients consulted relatively late and presented with a more advanced stage of
the disease. History of ocular allergy and eye rubbing were significant risk factors. Improving awareness of this
condition must be emphasized to detect keratoconus earlier.
Keratoconus
;
Cornea
;
Demography
;
Philippines
3.Preparation of an ophthalmic formulation of TPGS-modified insulin-loaded liposomes and its in vitro corneal permeation and pharmacokinetics in rabbit eyes.
Journal of Southern Medical University 2023;43(5):832-838
OBJECTIVE:
To prepare vitamin E polyethylene glycol 1000 succinate (TPGS)-modified insulin-loaded liposomes (T-LPs/INS) and evaluate its safety, corneal permeability, ocular surface retention and pharmacokinetics in rabbit eyes.
METHODS:
The safety of the preparation was investigated in human corneal endothelial cells (HCECs) using CCK8 assay and live/dead cell staining. In the ocular surface retention study, 6 rabbits were randomized into 2 equal groups for application of fluorescein sodium dilution or T-LPs/INS labeled with fluorescein in both eyes, which were photographed under cobalt blue light at different time points. In the cornea penetration test, another 6 rabbits divided into 2 groups for application of Nile red diluent or T-LPs/INS labeled with Nile red in both eyes, after which the corneas were harvested for microscopic observation. In the pharmacokinetic study, 2 groups of rabbits (n=24) were treated with eye drops of T-LPs/INS or insulin, and the aqueous humor and cornea were collected at different time points for measurement of insulin concentrations using enzyme linked immunosorbent assay. DAS2 software was used to analyze the pharmacokinetic parameters.
RESULTS:
The prepared T-LPs/INS showed good safety in cultured HCECs. Corneal permeability assay and fluorescence tracer ocular surface retention assay demonstrated a significantly higher corneal permeability of T-LPs/INS with a prolonged drug residence in the cornea. In the pharmacokinetic study, insulin concentrations in the cornea at 6, 15, 45, 60, and 120 min (P < 0.01) and in the aqueous humor at 15, 45, 60, and 120 min after dosing were significantly higher in T-LPs/INS group. The changes in insulin concentrations in the cornea and aqueous humor were consistent with a two-compartment model in T-LPs/INS group and with the one-compartment model in the insulin group.
CONCLUSION
The prepared T-LPs/INS shows an improved corneal permeability, ocular surface retention capacity and eye tissue concentration of insulin in rabbits.
Humans
;
Animals
;
Rabbits
;
Insulin
;
Liposomes
;
Endothelial Cells
;
Lipopolysaccharides
;
Vitamin E
;
Cornea
;
Fluorescein
4.Clinical profile and corneal complications of staphylococcal blepharitis at the Philippine General Hospital
Ruben Lim Bon Siong ; Pablito F. Sandoval Jr. ; George Michael N. Sosuan
Acta Medica Philippina 2023;57(2):44-49
Objectives:
Staphylococcal blepharitis is a common ocular condition that can cause significant visual morbidities due to corneal complications. This study described the clinical profile of patients with staphylococcal blepharitis seen in a tertiary referral eye center, and determined the frequency and the type of corneal complications, the possible reasons for the delay in diagnosis, and the management prior to the consult.
Methods:
This study was a single-center, five-year retrospective case series design. The charts of all patients from January 2016 to December 2021 with the diagnosis of staphylococcal blepharitis seen at the External Disease and Cornea Clinic of the Philippine General Hospital that have fulfilled the inclusion and exclusion criteria were included. The data extracted were age, sex, chief complaint, laterality, time of onset of symptoms to consult, previous consults, lid and lid margin findings, conjunctival and corneal findings, pre- and post-treatment uncorrected distance visual acuity, duration of follow-up, and treatments received.
Results:
Fifty-five (55) charts out of 107 charts with a diagnosis of staphylococcal blepharitis were included. Eighty percent (80%) or 44 patients had bilateral disease. Ninety-nine (99) eyes of 55 patients were analyzed. The median age of the study population was 19 years. Sixty-seven percent (67%) were female, and 33% were male. The mean duration of follow-up at the External Disease and Cornea Clinic was 10.8 ± 14.61 months. Corneal opacity, eye redness, and blurring of vision comprised 70% of the reasons for consult. The mean time from the onset of symptoms to consult was 18.36 ± 25.69 months. Sixty-seven percent (67%) had prior consults elsewhere and 45% came in with a different diagnosis. Seventy-eight (78) eyes had fibrin or crust on the lashes. Fifty percent (50%) of the eyes had concomitant conjunctivitis, while 30% had meibomitis. Fifty-eight percent (58%) of patients had corneal complications. Seventy-two percent (72%) of eyes had bilateral involvement. The median age of patients with corneal complications subgroup was 13 years. The most common corneal complications noted were neovascularization, phlyctenulosis, pannus formation, and marginal infiltrates or ulcers. Twenty-two percent (22%) of all study eyes had visually disabling corneal complications like corneal ulcer, descemetocele, corneal perforation, and corneal scar. Ninety percent (90%) of the patients received standard medical treatment and three patients underwent penetrating keratoplasty. The mean uncorrected distance visual acuity at initial consult of eyes with corneal complication was 20/55 (LogMAR 0.43 ± 0.51) and 20/35 (LogMAR 0.25 ± 0.40) after treatment (p = 0.032).
Conclusion
Staphylococcal blepharitis was most prevalent among young female patients, and it affected both eyes. Almost all patients manifested the typical lid margin lesions. Nearly 60% of the patients presented with corneal complications and 22% had corneal lesions that were potentially blinding. Close to 50% had delay in treatment due to misdiagnosis.
blepharitis
;
staphylococcus
;
cornea
;
blindness
5.Mechanism of gigantol in transmembrane transport in human lens epithelial cells.
China Journal of Chinese Materia Medica 2023;48(7):1936-1942
Gigantol is a phenolic component of precious Chinese medicine Dendrobii Caulis, which has many pharmacological activities such as prevent tumor and diabetic cataract. This paper aimed to investigate the molecular mechanism of gigantol in transmembrane transport in human lens epithelial cells(HLECs). Immortalized HLECs were cultured in vitro and inoculated in the laser scanning confocal microscopy(LSCM) medium at 5 000 cells/mL. The fluorescence distribution and intensity of gigantol marked by fluorescence in HLECs were observed by LSCM, and the absorption and distribution of gigantol were expressed as fluorescence intensity. The transmembrane transport process of gigantol in HLECs were monitored. The effects of time, temperature, concentration, transport inhibitors, and different cell lines on the transmembrane absorption and transport of gigantol were compared. HLECs were inoculated on climbing plates of 6-well culture plates, and the ultrastructure of HLECs was detected by atomic force microscopy(AFM) during the transmembrane absorption of non-fluorescent labeled gigantol. The results showed that the transmembrane absorption of gigantol was in time and concentration-dependent manners, which was also able to specifically target HLECs. Energy and carrier transport inhibitors reduced gigantol absorption by HLECs. During transmembrane process of gigantol, the membrane surface of HLECs became rougher and presented different degrees of pits, indicating that the transmembrane transport of gigantol was achieved by active absorption of energy and carrier-mediated endocytosis.
Humans
;
Lens, Crystalline/pathology*
;
Cataract/prevention & control*
;
Bibenzyls/pharmacology*
;
Epithelial Cells
;
Cells, Cultured
;
Apoptosis
6.Advances in interdisciplinary medical and engineering research of intraocular lens surface modifications to prevent posterior capsule opacification.
Journal of Central South University(Medical Sciences) 2022;47(12):1754-1762
Posterior capsule opacification (PCO), a common complication after cataract surgery, impacts a patient's long-term visual quality to various degrees. Although a neodymium:yttrium aluminum garnet (Nd:YAG) laser posterior capsulotomy is a very effective treatment, it may lead to a serial of complications. Accordingly, the search for simple, safe, and effective methods to prevent PCO has received widespread attention. Various researchers are committed to the interdisciplinary collaboration between medicine and engineering fields, such as functionalizing the surface of the intraocular lens (IOL) via supercritical fluid impregnation, coating the surface of the IOL, high-concentration drug immersion, and application of a drug delivery system, to effectively reduce the incidence and severity of PCO.
Humans
;
Capsule Opacification/surgery*
;
Lens Implantation, Intraocular
;
Cataract/etiology*
;
Lens Capsule, Crystalline/surgery*
;
Lenses, Intraocular/adverse effects*
;
Treatment Outcome
;
Postoperative Complications
;
Prosthesis Design
7.Effects of SMILE with different residual stromal thicknesses on corneal biomechanical properties of rabbits in vivo.
Yuan JIA ; Rui HE ; Xiaona LI ; Yaowen SONG ; Junchao WEI ; Hongwei QIN ; Xin YANG ; Weiyi CHEN
Journal of Biomedical Engineering 2022;39(4):679-684
Femtosecond laser small incision lenticule extraction (SMILE) with different residual stromal thicknesses (RST) is set to investigate its effect on corneal biomechanical properties of rabbits in vivo. In this study, 24 healthy adult Japanese rabbits were randomly divided into group A and B. The RST of group A was set 30% of the corneal central thickness (CCT), and the RST of group B was 50% of the CCT. The thickness of the corneal cap in both groups was set one third of CCT. Corneal visualization Scheimpflug technology (Corvis ST) and Pentacam three-dimensional anterior segment analyzer were used to determine corneal biomechanical and morphological parameters before surgery, and 1 week, 1 month and 3 months after surgery. Pearson correlation analysis was used to analyze factors affecting corneal biomechanical parameters after SMILE. The results showed that the corneal stiffness of group A was significantly higher than that of group B at 1 week and 1 month after surgery, and most biomechanical parameters returned to preoperative levels at 3 months postoperatively. The results of correlation analysis showed that postoperative CCT and RST were the main factors affecting corneal biomechanical parameters after SMILE. There was no significant difference in corneal posterior surface height (PE) between 3 months after surgery and before surgery in both two groups. It indicates that although the ability to resist deformation of cornea decreases in SMILE with thicker corneal cap and less RST, there is no tendency to keratoconus, which may be related to the preservation of more anterior stromal layer.
Animals
;
Biomechanical Phenomena
;
Cornea/surgery*
;
Postoperative Period
;
Rabbits
8.Relationship between time in range and corneal nerve fiber loss in asymptomatic patients with type 2 diabetes.
Weijing ZHAO ; Jingyi LU ; Lei ZHANG ; Wei LU ; Wei ZHU ; Yuqian BAO ; Jian ZHOU
Chinese Medical Journal 2022;135(16):1978-1985
BACKGROUND:
Corneal confocal microscopy (CCM) is a noninvasive technique to detect early nerve damage of diabetic sensorimotor polyneuropathy (DSPN). Time in range (TIR) is an emerging metric of glycemic control which was reported to be associated with diabetic complications. We sought to explore the relationship between TIR and corneal nerve parameters in asymptomatic patients with type 2 diabetes (T2DM).
METHODS:
In this cross-sectional study, 206 asymptomatic inpatients with T2DM were recruited. After 7 days of continuous glucose monitoring, the TIR was calculated as the percentage of time in the glucose range of 3.9 to 10.0 mmol/L. CCM was performed to determine corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length (CNFL). Abnormal CNFL was defined as ≤15.30 mm/mm 2 .
RESULTS:
Abnormal CNFL was found in 30.6% (63/206) of asymptomatic subjects. Linear regression analyses revealed that TIR was positively correlated with CCM parameters both in the crude and adjusted models (all P < 0.05). Each 10% increase in TIR was associated with a 28.2% (95% CI: 0.595-0.866, P = 0.001) decreased risk of abnormal CNFL after adjusting for covariates. With the increase of TIR quartiles, corneal nerve fiber parameters increased significantly (all P for trend <0.01). The receiver operating characteristic curve indicated that the optimal cutoff point of TIR was 77.5% for predicting abnormal CNFL in asymptomatic patients.
CONCLUSIONS
There is a significant independent correlation between TIR and corneal nerve fiber loss in asymptomatic T2DM patients. TIR may be a useful surrogate marker for early diagnosis of DSPN.
Humans
;
Diabetes Mellitus, Type 2/complications*
;
Cross-Sectional Studies
;
Blood Glucose Self-Monitoring
;
Blood Glucose
;
Nerve Fibers
;
Diabetic Neuropathies
;
Cornea
;
Microscopy, Confocal/methods*


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