Translational Vision Science & Technology最新文献

Purpose: To investigate the association between aqueous humor (AH) suppressant eye drops and the concentration of aflibercept at 1 month after intravitreal injection.

Methods: This retrospective study included 17 eyes of 17 patients with neovascular age-related macular degeneration (nAMD) who used eye drops for their glaucoma and received their first intravitreal aflibercept (IVA) at two centers between July 2013 and November 2020. As controls, we enrolled 40 age-, sex-, and axial length-matched eyes of 40 patients with nAMD who were not using any medication that would affect AH circulation. AH was collected 1 month after the first IVA. Aflibercept levels were measured by enzyme-linked immunosorbent assay and were compared between controls and cases using the Kruskal-Wallis test and Dunn's test. The drugs were categorized into two groups based on their mechanism of action on the AH: outflow drugs (e.g., prostaglandin analog) and inflow drugs (e.g., carbonic anhydrase inhibitor, beta-blockers, and alpha-2 agonists).

Results: Mean (interquartile range) aflibercept levels in the AH in controls and in cases who used outflow and inflow drugs were 6.83 µg/mL (1.94-10.34), 9.93 µg/mL (2.58-17.44), and 15.95 µg/mL (7.20-22.57), respectively. A Kruskal-Wallis test showed a significant difference among the control, inflow, and outflow drugs (P = 0.0075). Dunn's test showed that aflibercept levels in the aqueous humor were significantly higher in cases using inflow drugs compared to both controls and cases using outflow drugs (P = 0.0085 and P = 0.044, respectively).

Conclusions: Aflibercept levels in the AH 1 month after the first IVA were higher in cases using eye drops that reduce AH secretion than in controls.

Translational relevance: Our results, together with previous studies in animals, suggest that combined use of these eye drops might extend the half-life of intravitreally injected drugs.

Purpose: To evaluate the safety and efficacy of the magnetic levator prosthesis (MLP) relative to active control with KT Tape, an elastic therapeutic tape used clinically to mechanically open the lids, and to a sham MLP worn in-office only.

Methods: This was a double-masked, randomized crossover single-center trial of patients with severe unilateral or bilateral paralytic blepharoptosis defined as occlusion of the visual axis without frontalis recruitment. Patients were allocated to MLP or tape first and then crossed over after 2 weeks of use and a 2-week washout. Primary outcome was maximum eyelid closure on spontaneous blink measured in video frames with ImageJ. Primary patient-reported outcome was the Glasgow Benefit Inventory and, secondarily, comparison of the amount of eye opening and proportions of complete volitional blinks.

Results: Of 16 patients randomized, 15 completed the crossover. MLP and tape equally improved eye opening over sham (MLP, 6.8 mm [95% confidence interval (CI), 5.2-8.4]; tape, 7.0 mm [5.4-8.6]; sham, 3.9 mm [2.3-5.5], all P < 0.001). Spontaneous blinks were significantly better with MLP (2.4 mm [95% CI, 1.5-3.7] compared to tape, 4.1 mm [2.6-6.5], P < 0.001). Incomplete volitional blinks were much more common when wearing tape compared to when wearing the MLP (P < 0.001), which was not different from sham. There was a significant perceived benefit of both MLP and tape (P < 0.001). There were three related nonserious adverse events over 3539 hours of tape use and two related nonserious adverse events over 4632 hours of MLP use.

Conclusions: The MLP was superior to KT tape and sham for the treatment of severe blepharoptosis.

Translational relevance: First randomized controlled clinical trial of the MLP. (https://clinicaltrials.gov/study/NCT04678115?cond=Blepharoptosis&term=kinesiotape&rank=1, NCT04678115).

Purpose: A human model able to simulate the manifestation of corneal endothelium decompensation could be advantageous for wound healing and future cell therapy assessment. The study aimed to establish an ex vivo human cornea endothelium wound model where endothelium function can be evaluated by measuring corneal thickness changes.

Methods: The human cornea was maintained in an artificial anterior chamber, with a continuous culture medium infusion system designed to sustain corneal endothelium and epithelium simultaneously. The corneal thickness was used to assess corneal endothelial cell function. Immunostaining was used to evaluate cell viability and endothelial cell marker expression, ZO-1 and Na/K ATPase.

Results: Human corneas with intact corneal endothelium were maintained in the ex vivo model for 28 days, showing normal corneal thickness with a clear and transparent appearance. Corneal endothelial cells were alive and expressed ZO-1 and Na/K ATPase at the end of the organ culture. The endothelium wounded corneas showed persistent corneal edema with an increase in corneal thickness at 654.6 ± 31.7 µm. Staining results showed that no cells migrated to cover the wound and no expression of ZO-1 and Na/K ATPase on the posterior surface of the cornea was found.

Conclusions: This study provided a novel method to establish an ex vivo human cornea organ culture model, where corneal endothelium function can be evaluated by accessing the corneal thickness.

Translational relevance: The ex vivo model established in this study can provide an alternative to the animal model in studying corneal endothelium decompensation.

Purpose: To characterize frequency-dependent wave speed dispersion in the human cornea using microliter air-pulse optical coherence elastography (OCE), and to evaluate the applicability of Lamb wave theory for determining corneal elastic modulus using high-frequency symmetric (S0) and anti-symmetric (A0) guided waves in cornea.

Methods: Wave speed dispersion analysis for transient (0.5 ms) microliter air-pulse stimulation was performed in four rabbit eyes ex vivo and compared to air-coupled ultrasound excitation. The effects of stimulation angle and sample geometry on the dispersion were evaluated in corneal phantoms. Corneal wave speed dispersion was measured in 36 healthy human eyes in vivo.

Results: Air-pulse-induced dispersion was comparable to ultrasound-induced dispersion between 0.7 and 5 kHz (mean-difference ± 1.96 × SD: 0.006 ± 0.5 m/s) in ex vivo rabbit corneas. Stimulation 0° relative to the surface normal generated A0 Lamb waves in corneal tissue phantoms, while oblique stimulation (35° and 65°) generated S0 waves. Stimulating normal to the human corneal apex in vivo (0°) induced A0 waves, plateauing at 10.87 to 13.63 m/s at 4 kHz, and when obliquely stimulated at the periphery (65°), produced S0 waves, plateauing at 13.10 to 15.98 m/s at 4 kHz.

Conclusions: Air-pulse OCE can be used to measure human corneal Lamb wave dispersion of A0 and S0 propagation modes in vivo. These modes are selectively excited by changing the stimulation angle. Accounting for wave speed dispersion enables reliable estimation of corneal elastic modulus in vivo.

Translational relevance: This work demonstrates the feasibility of air-pulse stimulation for robust OCE measurements of corneal stiffness in vivo for disease detection and therapy evaluation.

Purpose: The purpose of this study was to evaluate the correlation between axial length (AL) and retinal oxygen dynamic parameters in adult patients.

Methods: This was an observational cross-sectional study with 79 Chinese adults with myopia aged 18 to 37 years. All participants underwent AL measurements, cycloplegic refraction, and other ophthalmic examinations. Additionally, the retinal oxygen kinetics imaging and analysis (ROKIA) system was utilized to obtain the retinal oxygen dynamic parameters of all patients. Simple and multiple linear regression tests were used to assess the correlation between various oxygen dynamic parameters and AL.

Results: The mean age, AL, and spherical equivalent (SE) of subjects were 26.32 ± 5.4 years, 25.78 ± 1.06 mm, and -5.13 ± 2.1 diopters (D), respectively. The Pearson correlation coefficients among AL and retinal oxygen delivery (DO2) and retinal oxygen metabolism (MO2) were -0.44 (95% confidence interval = -0.24 to -0.60, P < 0.001), -0.26 (95% confidence interval = -0.04 to -0.46, P = 0.02), respectively. The group with high myopia exhibited lower DO2 and higher oxygen extraction fraction (OEF) compared with the group with moderate myopia, and no significant difference was observed in MO2 between the two groups. In multivariate analyses adjusting for age, sex, intraocular pressure (IOP), and anterior chamber depth (ACD), a longer AL was significantly associated with decreased DO2 (standardized regression coefficient B = -0.47, P < 0.001).

Conclusions: Retinal oxygen dynamic parameters, including DO2 and MO2, were decreased with longer AL in myopic eyes. Patients with high myopia demonstrated an elevated OEF than those with moderate myopia.

Translational relevance: This study demonstrated that the retinal oxygen metabolism changes in myopia, as confirmed using a novel device that quantifies retinal oxygen dynamic parameters and provides a new monitoring approach for other hypoxic retinal diseases.

Purpose: Understanding the impact of vision impairment on dynamic tasks requiring visual processing is crucial for developing effective adaptive strategies that support individuals with vision impairment in optimizing their performance in natural tasks. This study aimed to establish the gaze patterns used by individuals with vision impairment when hitting a moving target.

Methods: Nineteen tennis players with vision impairment were recruited and their eye and head movements were tracked while they returned tennis serves.

Results: Participants used a variety of different strategies to track the ball visually, dictated largely by the nature of their impairment rather than its severity. Cluster analysis showed distinct strategies based on the type of vision impairment: those with peripheral vision loss foveated the ball closely and avoided predictive eye movements; those with poor oculomotor control initially tracked the ball but lagged as it approached; and those with central vision loss used a variety of strategies that did not align with the use of a single preferred retinal locus: some tracked the ball using a single preferred location in their peripheral vision, some switched the area of retina used to track the ball, and another did not move their gaze at all.

Conclusions: Tennis players with vision impairment adopt a variety of impairment-specific adaptations to their gaze-tracking strategies, enabling them to successfully hit an approaching tennis ball despite severe vision impairments.

Translational relevance: This study provides insight into the impairment-specific gaze strategies that well-adapted individuals with vision impairment adopt when hitting a moving target.

The introduction of optical coherence tomography (OCT) in the 1990s revolutionized diagnostic ophthalmic imaging. Initially, OCT's role was primarily in the adult ambulatory ophthalmic clinics. Subsequent advances in handheld form factors, integration into surgical microscopes, and robotic assistance have expanded OCT's utility and impact outside of its initial environment in the adult outpatient ophthalmic clinic. In this review, we cover the use of OCT in the neonatal intensive care unit (NICU) environment with a handheld OCT, recent developments in intraoperative OCT for data visualization and measurements, and recent work and demonstration of robotically aligned OCT systems outside of eye clinics. Of note, advances in these areas are a legacy of our colleague, the late Joseph Izatt. OCT has been an important innovation for ocular diagnostics, and these advances have helped it continue to extend in new directions.

Purpose: Although the lens undoubtedly plays a major role in presbyopia, altered lens function could be in part secondary to age-related changes of the ciliary muscle. Ciliary muscle changes with accommodation have been quantified using optical coherence tomography, but so far these studies have been limited to quantifying changes in ciliary muscle thickness, mostly at static accommodative states. Quantifying ciliary muscle thickness changes does not effectively capture the dynamic anterior-centripetal movement of the ciliary muscle during accommodation. To address this issue, we present a method to quantify the movement of the ciliary muscle during accommodation using trans-scleral optical coherence tomography images obtained dynamically.

Methods: An image processing framework including distortion correction, geometric transformation, and Procrustes analysis, was used to quantify the anterior-centripetal movement of the ciliary muscle apex and centroid during accommodation. The method was applied in a preliminary study to quantify ciliary muscle displacement and its relation to lens thickness change with accommodation on two young adults and two prepresbyopes.

Results: The magnitude and the direction relative to the pupil plane of the apex/centroid displacement in response to a two diopters (2D) stimulus were 0.16/0.20 mm at 11.3°/30.5° and 0.26/0.34 mm at 6.6°/33.2° for the young adults and 0.20/0.20 mm at 29.7°/40.6° and 0.24/0.40 mm at 33.0°/31.7° for the prepresbyopes, respectively.

Conclusions: This study demonstrates the feasibility of quantifying dynamic anterior-centripetal movement of the ciliary muscle during accommodation using optical coherence tomography. The method better captures the functional response of the muscle than the quantification of thickness changes.

Translational relevance: We provide a method that holds potential to better understand the age-related changes of the ciliary muscle on presbyopia.

Purpose: To clarify the clinical and imaging characteristics of Candida keratitis using in vivo confocal microscopy (IVCM) for improved early diagnosis and management.

Methods: A retrospective study of 40 patients with Candida keratitis at Beijing Tongren Hospital from January 2015 to December 2023 was conducted. Data included demographics, risk factors, clinical assessments, lab tests, and IVCM images. Ex vivo confocal microscopy and methylene blue staining of Candida colonies were also analyzed to complement the findings.

Results: Key risk factors identified were topical steroid use, intraocular surgery history, and systemic diseases. Common clinical signs included multifocal infiltration, cream-colored infiltration, and blurred boundary lesions. IVCM on 37 eyes (92.5%) consistently showed round, highly reflective Candida spores, and short rod-shaped spores in some cases. Spores exhibited two patterns: caviar-like clusters (51.4%) and sand-like dispersion (89.2%). Multifocal infiltration was significantly associated with a greater prevalence of clustered spores (75.0% vs. 33.3%; P < 0.05). Candida pseudo-hyphae appeared as beaded (91.7%) or lotus root-shaped (41.7%), highly reflective structures. These IVCM findings closely matched colony ex vivo confocal microscopy and light microscopy observations. After treatment, 45% of patients required surgery owing to minimal improvement in best-corrected visual acuity. Poor outcomes were linked to cream-colored infiltration, blurred lesions boundaries, hypopyon, high inflammatory cell density, and deep Candida infiltration (P < 0.05). Clustered spores suggested better outcomes, but lacked statistical significance (P > 0.05).

Conclusions: IVCM effectively identifies characteristic spores and pseudo-hyphae in Candida keratitis, facilitating early detection and timely management, particularly in cases with multifocal infiltration and blurred boundary lesions.

Translational relevance: IVCM works well for the early diagnosis of Candida keratitis, especially in cases of deep corneal stromal infiltration or corneal interface infection after corneal transplantation.

Purpose: To evaluate the refractive differences among school-aged children with macular or peripapillary fundus tessellation (FT) distribution patterns, using fundus tessellation density (FTD) quantified by deep learning (DL) technology.

Methods: The cross-sectional study included 1942 school children aged six to 15 years, undergoing ocular biometric parameters, cycloplegic refraction, and fundus photography. FTD was quantified for both the macular (6 mm) and peripapillary (4 mm) regions, using DL-based image processing applied to 45° color fundus photographs. Eyes exhibiting tessellation were classified into two groups: the macular distribution group had greater FTD in the macular area, while the peripapillary distribution group had higher FTD in the peripapillary area, allowing for a comparative analysis of axial length (AL), corneal radius, and refraction.

Results: Participants had a median age of 13 years and a median spherical equivalent (SE) of -0.75 D. The macular distribution group exhibited significantly larger AL (24.13 mm vs. 23.93 mm, P < 0.001) and more myopic refraction (-1.13 D vs. -0.75 D, P < 0.001) compared to the peripapillary group. A higher prevalence of macular-distributed FT was noted in the myopic groups (χ2 = 131.675, P < 0.001). SE negatively correlated with macular (r = -0.238) and peripapillary FTD (r = -0.195), while AL positively correlated with FTD in both regions (r = 0.308; r = 0.265) (all P < 0.001).

Conclusions: The macular FT distribution pattern is significantly associated with larger AL and greater myopic refraction in school-aged children, suggesting its potential as a marker for identifying children at risk of progressing myopia.

Translational relevance: DL analysis precisely identifies FT distribution patterns, potentially enhancing early detection of high-risk myopia in populations.