Translational Vision Science & Technology最新文献

Purpose: To evaluate the expression of small extracellular vesicle (sEV)-specific markers in retinoblastoma (RB) tumor tissue and to identify the RB-specific extracellular cargo as biomarker.

Methods: Twenty-five treatment-naïve, unilateral RB were included in the study from ophthalmic pathology achieves during January 2020 to December 2022. Demographics, histomorphology, and immunohistochemical analysis were performed on all the samples. The expression of the immunomarkers was graded as faint (+), moderate (++), or marked (+++) compared with immunohistochemistry controls.

Results: In the 25 enucleated RB eyes, CD63 (n = 11 [44%]) and TSG101 (n = 23 [92%]) were more prominently expressed sEV markers in the tumor. CD81 was the least expressed. Of the sEV cargo, HIF1a (n = 22, 88%) followed by KAT2B (n = 21 [84%]) showed increased expression in tumor cells with no expression in normal retina. Vascular endothelial growth factor A was seen in 48% of cases and was expressed in normal retina. All the markers showed heterogenous expression in the tumor.

Conclusions: Although sEV markers are expressed in tumor microenvironment, their expression is heterogenous in tumors. Of the EV markers, tetraspanin CD63 was predominantly expressed in tumor tissues as compared with CD9 and CD81. Among the previously identified EV cargo, HIF1a and KAT2B were found to be expressed in RB tumors, indicating their potential as biomarkers.

Translational relevance: KAT2B, previously identified as EV cargo, showed expression in tumor tissue, validating its biomarker potential.

Purpose: To identify factors influencing best corrected visual acuity (BCVA) prognosis in patients with AQP4-IgG+ neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON) after treating with high-dose intravenous methylprednisolone.

Methods: A total of 161 intravenous methylprednisolone (IVMP)-treated patients were randomized into training (n = 113) and internal validation (n = 48) sets at a ratio of 7:3. Using Least Absolute Shrinkage and Selection Operator regression, 16 candidate predictors were screened to construct a logistic model to predict follow-up BCVA after six months post-ON attack. Discrimination (area under curve [AUC]), calibration, and clinical net benefit (decision curve analysis [DCA]) were assessed.

Results: The final model included seven predictors: age, AQP4-IgG titer, non-ON attack history, baseline BCVA, mean deviation, macular ganglion cell inner plexiform layer thickness, and treatment window. AUCs were 0.904 (95% confidence interval [CI], 0.850-0.959) and 0.864 (95% CI, 0.761-0.967) in training and validation sets, respectively. Calibration curves indicated high consistency, and DCA demonstrated significant net benefit at 10%-90% risk thresholds.

Conclusions: The validated prediction model effectively stratifies IVMP-treated patients at risk of visual disability, enabling precision management.

Translational relevance: By converting heterogeneous prognostic factors into a practical prediction tool, this work empowers clinicians to deliver precision care for a blinding complication of NMOSD, directly reducing preventable visual disability.

Purpose: To characterize corneoscleral morphology in keratoconus versus normal eyes via anterior segment optical coherence tomography (AS-OCT) and investigate its relationship with Scheimpflug-based corneal tomography and corneal biomechanics.

Methods: This cross-sectional study included 43 keratoconus and 74 control eyes. AS-OCT imaging was conducted across superior, inferior, nasal, and temporal meridians at the corneoscleral limbus. Chord-based scleral and corneal curvature were assessed at 5 mm (SclCurv5, CorCurv5) and at 2.5 mm (SclCurv2.5, CorCurv2.5) from the scleral spur. The corneoscleral junction angle (CSJA) was also analyzed. Group and meridian differences were evaluated, and associations with corneal tomography (Pentacam) and biomechanics (Corvis ST) were explored.

Results: Keratoconic eyes exhibited a distinct corneoscleral architectural pattern compared to controls, characterized by greater vertical asymmetry in SclCurv5 and CorCurv5, as well as flatter inferior SclCurv2.5 and flatter inferior and temporal CorCurv5 (all P < 0.05). Within the keratoconus group, a larger superior CSJA was associated with a more favorable profile of corneal tomographic and biomechanical parameters, including lower maximum keratometry, exp(β) = 0.95, P = 0.002; a lower topographic keratoconus classification grade, exp(β) = 0.54, P = 0.038; and greater thickness-profile-integrated stiffness, as measured by Ambrósio's relational thickness horizontal, exp(β) = 1.10, P = 0.027.

Conclusions: Keratoconus involves significant alterations in corneoscleral architecture beyond the cornea itself. A larger superior CSJA emerged as a significant independent predictor of a milder disease phenotype among keratoconus patients.

Translational relevance: A larger superior CSJA may indicate a slower disease progression, aiding in personalized monitoring and management planning.

Purpose: The purpose of this study was to develop an optimized treatment for pathological myopia: a degradable cell-free suture-free tissue scaffold implant that reverses the excessive axial elongation and induces a therapeutic ridge.

Methods: A form-deprivation (FD) myopia model was established in New Zealand White rabbits. Comprised of gelatin methacryloyl and a poly-L-lactide microfiber film, the tissue scaffold was implanted onto the posterior sclera of FD eyes (model + implant group; n =12), compared with model-only (n = 12) and controls eyes (n = 24). Ocular dimensions were monitored via ultrasound. Safety was assessed by electroretinogram, intraocular pressure, and apoptosis assays. The histology structure of regenerated tissue and sclera was shown.

Results: The axial length in model + implant eyes was significantly shorter than model-only eyes and the control eyes since 2 weeks after the implantation (13.79 ± 0.23 mm, 15.15 ± 0.33 mm, and 14.70 ± 0.18 mm, P < 0.001) and maintained. The scaffold prompted the in situ regeneration of tissue mimicking the pseudo-lamellar arrangement of collagen fibers and major cell types found in native sclera, which formed an inward therapeutic ridge at the posterior sclera. The simulation indicated the ridge relieved outward macular traction significantly with minimum perturbation to stress distribution outside the central macula. Furthermore, collagen synthesis was prompted within the sclera itself.

Conclusions: This innovative strategy, which avoids the long-term complications of foreign body compression, suturing, or tension fixation, effectively reversed myopic eye elongation and induced a therapeutic ridge.

Translational relevance: Demonstration of a degradable scaffold implantation as a treatment for pathological myopia with potential for minimally invasive clinical application was presented.

Purpose: The purpose of this study was to evaluate clinical factors that could differentiate patients with Sjogren's disease-related dry eye (SDDE) from non-SDDE.

Methods: Patients with SDDE (n = 20), non-SDDE (n = 47), and healthy control participants (n = 29) were enrolled. Patients with dry eye were required to have physician-diagnosed dry eye disease for at least 6 months prior to the study. Sjogren's diagnosis was made according to 2016 Sjogren's disease criteria. Control participants had no known dry eye diagnosis or ocular and/or autoimmune disease. Several validated questionnaires regarding overall health and perception of health, mental status, review of systems, and ocular symptom were administered concurrently. Ocular surface and tear film parameters were evaluated using strict methodology.

Results: Each questionnaire, each section within a questionnaire, and each question within a section were evaluated. Of systemic symptom questionnaires, only Profile of Fatigue and Discomfort Questionnaire (PROFAD) differentiated between SDDE and non-SDDE (10.5 vs. 5.8, P = 0.003). Among four Sjogren's Foundation recommended review of systems questions, only dry mouth differentiated patients with SDDE from non-SDDE (90% vs. 53%, P = 0.004). No mental health or ocular symptom questionnaires were different between SDDE versus non-SDDE. Among clinician-measured ocular surface parameters, only corneal fluorescein (2.5 vs. 1.0, P = 0.006) and conjunctival lissamine green (2.0 vs. 1.0, P = 0.001) staining scores were significantly worse in patients with SDDE compared to non-SDDE.

Conclusions: Ocular staining and dry mouth complaints were strongly associated with SDDE.

Translational relevance: Ocular surface vital dye staining and inquiring about dry mouth complaints can be helpful to determine whether Sjogren's laboratory work-up should be considered in patients presenting with dry eye disease.

Purpose: Current treatment strategies for glaucoma, the leading cause of irreversible blindness, only target intraocular pressure (IOP) but not the underlying retinal ganglion cell degeneration. IOP management is not always effective, necessitating neuroprotective strategies. Lysophosphatidic acid (LPA) is an extracellular signaling molecule implicated in modulating inflammation. It exerts its signaling effects through its receptors (LPAR1-6). Here we test the efficacy of PIPE-791, an LPAR1-selective antagonist, in conferring neuroprotection and modulating neuroinflammation in glaucoma.

Methods: A bead-induced rat ocular hypertension (OHT) model of glaucoma was used to test PIPE-791 (administered intraperitoneally at 3 mg/kg dosing). We monitored IOP through tonometry and evaluated PIPE-791's neuroprotective capacity by studying retinal ganglion cell survival using cell counting and its effects on retinal vasculature, immune cell numbers and cytokine profile.

Results: PIPE-791 had no effect on IOP in normotensive (NT) or OHT rat eyes. It also did not have any neuroprotective effect on retinal ganglion cell survival, nor did it normalize the changes in retinal vasculature observed in OHT retinas. Although PIPE-791 treatment increased microglial numbers in NT retinas, there was no effect in OHT retinas. Cytokine array profiling also revealed no significant effects for PIPE-791 on the cytokine changes between the NT and OHT retinas. These lack of changes could potentially be explained by the fact that LPAR1 protein levels are decreased in OHT retinas.

Conclusions: Our data suggests that targeting LPAR1 through pharmacological means does not provide neuroprotection or modulate neuroinflammation favorably in glaucoma.

Translational relevance: Our study provides evidence that pharmacological targeting of LPAR1 as a potential therapeutic avenue in glaucoma may not be beneficial.

Purpose: To evaluate the benefit of using OPTIMEyes, an Interactive Machine Learning (IML) platform for annotation of ophthalmology images, along three axes: efficiency, uniformity, and noninferiority when compared to unassisted segmentation of geographic atrophy (GA) from fundus autofluorescence.

Methods: We enrolled 10 annotators and collected 110 fundus autofluorescence images from patients with GA. We obtained ground truth GA segmentations from an expert retinal specialist and used 100 images to train the OPTIMEyes Artificial Intelligence (AI) segmentation model and 10 images to compare unassisted segmentation with AI-assisted segmentation. During data analysis, we excluded two annotators due to highly inconsistent segmentations. We measured annotation time in seconds and compared segmentations using the DICE score.

Results: We showed that AI assistance shortened average annotation time by 96 seconds when compared to unassisted segmentation and helped produce more similar segmentations across annotators while maintaining similar DICE score between the annotators' segmentations and the expert's (mean DICE difference 0.02). Additionally, challenging images (i.e., unassisted DICE score < 0.3) showed the highest improvements in segmentation quality (mean DICE improvement: 0.38).

Conclusions: We showed how OPTIMEyes can improve segmentation of GA from fundus autofluorescence by shortening annotation time and improving agreement across annotators without sacrificing segmentation quality.

Translational relevance: OPTIMEyes can be integrated in clinician's workflows to provide automated segmentations that can be easily manually improved, increasing the task's effectiveness and efficiency. In addition, it enables the efficient collection of high-quality manually labeled large imaging datasets that can be of great interest to the research community.

Purpose: The purpose of this study was to determine whether neutrophil extracellular trap (NET)-related markers are elevated in the aqueous humor of patients with glaucoma compared with healthy controls.

Methods: We performed a case-control study of patients scheduled to undergo cataract extraction and/or glaucoma surgery from 2020 to 2022.

Results: One hundred seventy-seven eyes were included: 127 were healthy controls, 43 were patients with glaucoma, and 7 were patients with uveitis. Pro-inflammatory markers were elevated in glaucomatous aqueous humor as compared with controls including: interleukin-1β (IL-1β; 1.31 pg/mL, interquartile range [IQR] = 1.87 vs. 1.12 pg/mL, IQR = 0.55, P < 0.0001), interferon gamma-inducible protein 10 (IP-10; 61.4 pg/mL, IQR = 106 vs. 25.9 pg/mL, IQR = 36.4, P = 0.0002), IL-8 (5.46 pg/mL, IQR = 5.10 vs. 2.52 pg/mL, IQR = 2.16, P < 0.0001), neutrophil gelatinase-associated lipocalin (NGAL; 2760 pg/mL, IQR = 4450 vs. 1690 pg/mL, IQR = 1370, P < 0.0001), and eDNA (0.0324 µg/mL, IQR = 0.0400 vs. 0.025 µg/mL, IQR = 0.0120, P < 0.0001). Furthermore, the glaucoma group had higher levels of IgG (3470 ng/mL, IQR = 4130 vs. 2370 ng/mL, IQR = 1800, P < 0.0001), IgA (188 ng/mL, IQR = 315 vs. 84.9 ng/mL, IQR = 198, P = 0.001), and IgM (3.45 ng/mL, IQR = 2.32 vs. 3.00 ng/mL, IQR = 0.880, P = 0.033) within the aqueous humor than the controls.

Conclusions: Multiple levels of the inflammatory pathway are implicated in glaucoma, including inflammatory cytokines (IL-1β), T-cell mediators (IP-10), neutrophil chemoattractant (IL-8), NET-associated molecules (NGAL and eDNA), and the adaptive immune response (immunoglobulins IgM, IgG, and IgA). Findings support further investigation of immunomodulatory approaches to treatment of glaucoma.

Translational relevance: This study looks at the basic inflammatory pathways and biomarkers relevant to glaucoma.

Purpose: To translate and validate a Chinese version of the Low Luminance Questionnaire (LLQ).

Methods: The original LLQ was translated into Chinese by two ophthalmologists and back-translated by a professional translator. Between 2022 and 2023, participants with visual impairment were recruited from Zhongshan Ophthalmic Center. The method of successive dichotomizations (MSD) was used to assess the separation index, reliability, item misfit, and differential item functioning (DIF) of the questionnaire; principal component analysis was also used to assess unidimensionality. Linear regression analyzed the relationship between participant demographics and MSD person measures based on the Chinese LLQ.

Results: A total of 173 participants (67.05% female) with an average age of 65.73 years were included, and all completed the Chinese version of the LLQ. After taking into account item fit, content validity, targeting, and cultural adaptation to the Chinese context, eight items were removed, yielding a final 24-item Chinese LLQ (LLQ-24). This version showed good separation (person, 3.47; item, 7.61) and reliability (person, 0.92; item, 0.98), although person-item targeting was suboptimal, with person measures averaging 1.63 logits higher than item measures. A few items showed DIF across age and gender. Participants with worse visual acuity and those with cataract had lower scores on the LLQ-24.

Conclusions: The 24-item Chinese LLQ provides a useful tool with fair validity and reliability to assess low luminance visual difficulties in the Chinese population.

Translational relevance: The Chinese LLQ enables eyecare professionals to more accurately assess and manage vision-related conditions in low-light environments.

Purpose: To investigate whether iron overload is associated with increased risk of ocular hypertension (OHT), primary open-angle glaucoma (POAG), and normal-tension glaucoma (NTG).

Methods: A retrospective cohort study was conducted using the TriNetX multinational database. Patients ≥ 40 years old without prior glaucoma were classified into iron overload and non-iron overload groups. Propensity score matching (1:1) was applied to balance demographics, comorbidities, and medication use. Cox proportional hazards regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Kaplan-Meier analyses evaluated cumulative incidence over 5 years.

Results: Among 63,577 matched pairs, iron overload was significantly associated with elevated risks of OHT (HR = 1.32; 95% CI, 1.06-1.66) and POAG (HR = 1.65; 95% CI, 1.32-2.06). For NTG, the HR was also above 1 (1.31), but the wide confidence interval (95% CI, 0.74-2.33) likely reflects the small number of outcome events. Stratified and sensitivity analyses, including those with ferritin > 500 ng/mL, showed consistent associations across age, sex, and comorbidity subgroups.

Conclusions: Iron overload is linked to a significantly increased risk of glaucoma and ocular hypertension. These findings highlight systemic iron dysregulation as a modifiable risk factor for glaucomatous disease.

Translational relevance: Our findings suggest that patients with iron overload may benefit from targeted ophthalmologic referral, particularly those with visual symptoms or additional risk factors. The association between iron dysregulation and glaucoma highlights opportunities for interdisciplinary care, risk stratification using ferritin, and mechanistic research into ferroptosis-driven neurodegeneration, with implications for iron-targeted neuroprotective strategies.