PurposeTo develop and validate a self-reconstructed anterior segment optical coherence tomography (AS-OCT) thickness difference map to precisely quantify corneal changes, using lenticule thickness in small-incision lenticule extraction (SMILE) as a model.MethodsThis retrospective study included 22 patients (44 eyes) who underwent SMILE. Using a self-developed R software script, we reconstructed corneal and stromal thickness difference maps from 40,000-point raw AS-OCT data spanning a 10-mm central corneal diameter. The estimated lenticule thickness (ELT) was defined as the maximum thickness change and compared against planned lenticule thickness (PLT) from the VisuMax laser readout. We also compared ELTs derived from Pentacam Scheimpflug tomography at the thinnest and vertex points.ResultsAt 3 months postoperatively, the ELT retrieved form reconstructed corneal thickness difference map (CTDM) and stromal thickness difference map (STDM) from AS-OCT demonstrated smaller discrepancies with PLT (4.80 ± 9.85 µm and 1.53 ± 6.59 µm, respectively) compared to discrepancies between PLT and Pentacam thinnest point lenticule thickness (PTLT) and Pentacam vertex point lenticule thickness (PVLT) (14.21 ± 13.66 µm and 12.8 ± 13.88 µm) (both P < 0.001). STDM showed much stronger correlation with PLT (R2 = 0.88) than CTDM, PTLT, and PVLT (R2 = 0.87, 0.79, and 0.79, respectively) (analysis of variance, P = 0.039).ConclusionsThe self-reconstructed AS-OCT thickness difference map accurately measures ELT after SMILE, outperforming Scheimpflug tomography in precision and reliable monitoring of corneal thickness changes.Translational RelevanceThis technique enables accurate layer-specific corneal thickness monitoring, supporting safer surgical planning and enhanced assessment of postoperative or pathological corneal changes in clinical ophthalmology.

To quantify determinants of intergrader agreement for key retinal photography and optical coherence tomography (OCT) biomarkers in early to intermediate age-related macular degeneration (AMD) and to inform future consensus definitions and grading protocol. Single eyes from 269 participants with early to intermediate AMD were consecutively sampled. Retinal photographs were evaluated for the presence of large drusen and pigmentary abnormalities. OCT B-scans were graded for reticular pseudodrusen (RPD), outer retinal band abnormality (external limiting membrane [ELM], ellipsoid zone [EZ], and retinal pigment epithelium [RPE]), nascent geographic atrophy (nGA), intraretinal hyperreflective foci (IHRFs), hyporeflective drusen cores (hDCs), shallow irregular RPE elevations (SIREs), and drusenoid pigment epithelial detachment (DPED). Biomarkers were classified using a trinary certainty system: "definitely present" (≥90%), "questionably present" (50%-90%), or "absent" (<50%). The main outcome was odds of intergrader agreement from generalized estimating equations adjusting for intraparticipant correlations, biomarker type, and eye- and participant-level factors. Odds of agreement were comparable for large drusen, nGA, RPE abnormality, IHRF, and ELM abnormality; higher for RPD (odds ratio [95% confidence interval], 3.17 [1.56-6.45], P < 0.01); and lower for SIRE, EZ abnormality, pigmentary abnormalities, hDC, and DPED (up to 0.5 [0.32-0.78], P < 0.01). Agreement improved with higher grading certainty (1.4 [1.22-1.6], P < 0.0001) but declined with age (per decade, 0.8 [0.7-0.93], P < 0.01). Biomarker type, grading certainty, and participant age influence OCT agreement. Consensus definitions and grading protocols, including the use of high certainty thresholds (≥90%), may improve consistency. Implementing consensus definitions and protocols can improve agreement and strengthen the clinical utility of OCT biomarkers in AMD.

To evaluate the associations of hypertension history, blood pressure (BP) levels, and parameters with retinal vascular occlusion (RVAO) risk, and to identify potential mediating plasma proteins. The cohort study used data from 439,057 UK Biobank participants. Multivariable Cox regression was used to evaluate associations between incident RVAO and exposures: hypertension history (with stratification of control status and disease duration), hypertension stages (per 2017 guidelines), systolic BP (SBP), diastolic BP (DBP), mean arterial BP (MABP), and pulse pressure (PP). Mendelian randomization (MR) was subsequently used to assess causality and identify mediating plasma proteins. In observational analysis, hypertension history (uncontrolled and long/unknow duration), stage 1 hypertension, stage 2 hypertension, higher BP parameters (SBP, MABP, and PP) were associated with an increased risk of RVAO, whereas DBP showed no significant association. The MR analysis supported the causal relationships for hypertension history and SBP but not for DBP. Six plasma proteins were identified as potential mediators for the hypertension history, with secretory leukocyte peptidase inhibitor (SLPI) explaining the largest proportion of the effect (13.3%). Ankyrin Repeat and SOCS Box Containing 9 (ASB9) was found to mediate the effects for both hypertension history (3.56%) and SBP (4.31%) to RVAO. Hypertension history and elevated SBP were significant risk factors for RVAO. Specific plasma proteins, notably SLPI and ASB9, may serve as mediators and represent potential targets for therapeutic intervention. The identification of mediating plasma proteins, such as SLPI and ASB9, provides novel therapeutic targets and biomarkers for preventing RVAO among individuals with hypertension.

PurposeTo propose a novel deep learning–based methodology for drusen detection and quantification in early age-related macular degeneration (AMD) using retinal multispectral images. The retinal multispectral images highlight features in several nonoverlapping spectral bands that the deep learning models leverage for automatic drusen detection and quantification in dry AMD.MethodsThe proposed novel methodology comprises quality assessment of retinal images, region of interest extraction, drusen segmentation, and drusen quantification stages. Different deep learning models (such as UNet++ convolutional neural network with EfficientNetV2 encoder) have been implemented for these stages. A total of 170 drusen and 150 nondrusen retinal images (single eye) were split into four training and validation data sets to analyze the performance of a deep learning model for drusen segmentation.ResultsThe proposed methodology achieved an average score, recall, and precision of 0.691, 0.668, and 0.776, respectively, across all four validation sets. This work also analyzed the performance of the proposed deep learning model for discriminating drusen and drusen-like lesions, achieving a pixel-wise segmentation accuracy of 99.998%. The number and the diameter of the detected drusen were also computed. A Dice score distribution for drusen segmentation with different numbers and sizes of drusen per eye is also shown.ConclusionsThis work demonstrates that deep learning models applied to retinal multispectral images can provide accurate and clinically significant drusen segmentation and quantification, thereby facilitating early detection, longitudinal monitoring, and reduction of the risk of vision loss from AMD.Translational RelevanceDeep learning–assisted detection of drusen from multispectral retinal images will refine and improve clinical diagnosis of early nonexudative age-related macular degeneration.

PurposeTo model the jet flow of a 25G vitrectomy infusion cannula onto the opposite retina in a balanced salt solution–filled eye, calculate pressure and shear stress at the retina, and evaluate the biologic response to the localized increase of pressure on an ex vivo pig retina model.MethodsFluidics, pressure, and shear stress were calculated using computational fluid dynamics. Ten pig eyes within 4 hours of slaughter were prepared to receive a 10 mL/min flow for 1 or 3 minutes after removing the vitreous and inserting a 25G infusion cannula in the usual fashion. RNA transcripts of selected proteins involved in inflammation, oxidative stress, and apoptosis were amplified and measured.ResultsAt a 10 mL/min infusion flow rate, the average fluid velocity at outlet reached 1.33 m/s and pressure at impact site increased more than 2 mm Hg in a region approximately 1 mm wide. RNA transcripts of p65, nuclear factor κB, casp3, p53, inducible nitric oxide synthase, Keap1, Nrf2, and glial fibrillary acidic protein reached statistical significance on analysis of variance at the 0.01 level and interleukin-1b and NOX4 exceeded 2log2 units fold-change.ConclusionsThe jet flow generated by 25G vitrectomy infusion cannulas not only may compromise the surgeons’ view blowing on dyes and create potentially harmful perfluorocarbon liquid bubbles, it also reaches significant velocity and remarkable pressure at the impact site. RNA transcripts of proteins involved in inflammation, oxidative stress, and apoptosis significantly increase as soon as 1 and 3 minutes after flow starts.Translational RelevanceEvaluation of the infusion jet consequences on the retina lays the foundations for finding solutions that reduce pressure increase and tissue response.

PurposeTo compare the three-dimensional choroidal contour map of patients with neovascular age-related macular degeneration (nAMD) and their fellow eyes.MethodsThis cross-sectional study included 30 patients with nAMD in one eye and early/intermediate AMD in the fellow eye. Wide-field (12 × 12 mm) swept source optical coherence tomography volumetric scans were obtained. Choroidal inner boundaries (CIBs) and choroidal outer boundaries (COBs) were delineated based on our previously reported deep learning model. Best-fit spherical radius (R, mm) was calculated for CIB and COB and compared in both groups using paired t tests. The regional variation of RCIB and RCOB in different sectors (superior, inferior, nasal, temporal, and central) was compared. P values of ≤0.05 were considered statistically significant.ResultsThe mean RCIB was 32.8 ± 8.6 mm and 32.5 ± 9.4 mm in nAMD group and their fellow eyes, respectively (P = 0.80). Similarly, the mean RCOB was 31.3 ± 7.0 mm in the nAMD group with no statistically significant variation in their fellow eyes (early/intermediate AMD, 31.5 ± 9.0 mm; P = 0.88). Comparison of RCIB (nAMD, 15.0 ± 9.1 mm; fellow eye, 15.2 ± 10.4 mm; P = 0.91) and RCOB (nAMD, 13.6 ± 8.1 mm; fellow eye, 12.2 ± 9.0 mm; P = 0.48) in the central sector where AMD lesions were located was not significant. Intragroup sectoral comparisons of RCIB and RCOB in both groups were statistically significant (all P values < .01).ConclusionsRCIB and RCOB exhibited significant regional variations across different sectors in both eyes, including nAMD and fellow eyes. However, the comparison of RCIB and RCOB between the two groups was not significantly different.Translational RelevanceThe study of choroidal contour may help to understand the pathological changes in age-related macular degeneration.

PurposeQuantitative evaluation of three-dimensional (3D) choroidal contour at choroidal inner boundary (CIB) and choroidal outer boundary (COB) in central serous chorioretinopathy (CSCR) and fellow eyes of patients with unilateral CSCR.MethodsRetrospective study on 58 eyes of 29 patients with unilateral CSCR. Detailed examination and investigations including wide-field swept source optical coherence tomography (SS-OCT) were performed. Delineation of CIB and COB was performed using a hybrid method based on our previously validated deep learning and 3D smoothing methods for choroidal layer segmentation. Quantitative analysis of the surfaces was based on best-fit spherical radius (R). Statistical analysis was done using SPSS software.ResultsR CIB and R COB was significantly higher in CSCR eyes compared to fellow eyes (P = 0.001, 0.02). On sectoral analysis, central sector had the lowest R compared to all the other sectors in CSCR eyes (P < 0.001) and fellow eyes (P < 0.001). Within the group, R CIB > R COB in CSCR eyes (P = 0.001) and in fellow eyes (P = 0.014), and there was a high degree of correlation between RCIB and RCOB within a group (CSCR: r = 0.88, P < 0.001; fellow eyes: r = 0.87, P < 0.001).ConclusionsThis study shows CIB and COB to be flatter in CSCR eyes compared to fellow eyes. In both CSCR and fellow eyes, CIB is flatter than COB.Translational RelevanceStudying choroidal surfaces helps understand how predispositions and compensatory mechanisms to venous overloading may differ in CSCR and fellow eyes and how contour changes may serve as a biomarker for the disease.

PurposeTo develop and validate a novel method for quantifying blood flow velocity in ocular vessels using speckle pattern analysis in optical coherence tomography (OCT) images.MethodsWe developed an OCT-based methodology that quantifies flow velocity by analyzing speckle structures within OCT images to derive a relative flow value (RFV) based on the horizontal derivative of speckle patterns. A model eye with 150-µm capillary tubing was used to evaluate speckle pattern analysis at controlled flow rates of human and porcine blood. We assessed the correlation between RFV and actual flow velocities and examined measurement consistency across vessel sectioning angles varying ±20° from perpendicular.ResultsRFV exhibited a power-law relationship with actual flow velocities, RFV = 169.6 × (Actual Flow)0.264 (r2 = 0.983), and maintained accuracy without saturation up to 70 mm/s. Measurements remained consistent across vessel sectioning angles. Intraluminal speckle structures changed dynamically with flow velocity, and averaged images revealed characteristic hourglass profiles at higher velocities. In a patient with central retinal vein occlusion, RFV detected altered pulsatility and reduced venous flow, aligning with clinical expectations.ConclusionsThis speckle-based OCT method provides a non-invasive, depth-resolved approach for quantifying ocular blood velocity with minimal computational requirements. It holds potential for diagnosing and monitoring vascular abnormalities in ocular and systemic diseases. Further validation is necessary across diverse patient populations.Translational RelevanceThis method simplifies blood flow quantification, enhancing the role of OCT in hemodynamic assessment both ocularly and systemically.

PurposeTo evaluate the preclinical safety of a single treatment of a topical scleral cooling device.MethodsTwo Good Laboratory Practice prospective preclinical device safety studies were performed: study 1 in normal healthy rabbit eyes (n = 5) and study 2 in healthy rabbit eyes that underwent a surgically induced corneal epithelial defect (n = 3). Following sedation, eyes were treated for 10 minutes by applying the cooling device to the sclera. Key assessments for both studies included clinical observations, Schirmer's I and II tests, ophthalmic examinations, intraocular pressure (IOP) measurements, and histopathology. Study 1 assessments were performed on days −3, 7, 14, 21, 28, 42 (±2 days), and 56 (±2 days). In study 2, a 3-mm diameter corneal defect was created in both eyes of each animal 14 days after the cooling device application. Corneal fluorescein staining was monitored at 3, 6, 24, 30, 48, 54, and 72 hours after defect creation.ResultsMinimal changes in conjunctival redness, peripheral corneal haze, and fluorescein staining were observed, which completely self-resolved within 4 weeks after treatment. Schirmer's I and II and IOP results were within normal ranges in all animals. All epithelial defects in both groups had fully healed within 48 hours.ConclusionsNo adverse effects were observed within 8 weeks following a single scleral application of the topical cooling device in rabbit eyes.Translational RelevanceThis article introduces a novel ocular cooling device for the treatment of chronic ocular surface pain, a condition with a considerable unmet need for more effective therapies.