Journal Of Clinical & Experimental Ophthalmology[JOURNAL]
Sun
200 papers
Identification of tear lipid biomarkers in women with dry eye disease and the impact of intense pulsed light therapy: a case-control study.
Acera A, Ibarrondo O, Mateo-Orobia AJ … +9 more , Pereiro X, Abad-García B, López-Plandolit S, Ruzafa N, Romero M, Blasco-Martínez A, Rodríguez FD, Duran JA, Vecino E
BMC Ophthalmol · 2025 Sep · PMID 40890636 · Full text
BACKGROUND: The tear-film lipid layer (TFLL) constitutes the outermost barrier of the ocular surface, reducing evaporation and stabilising the tear film. In aqueous-deficient dry eye (ADDE) and Meibomian-gland dysfunctio...
BACKGROUND: The tear-film lipid layer (TFLL) constitutes the outermost barrier of the ocular surface, reducing evaporation and stabilising the tear film. In aqueous-deficient dry eye (ADDE) and Meibomian-gland dysfunction (MGD), compositional changes in the TFLL compromise this protective role. The present study was designed to characterise the tear-lipid fingerprints associated with ADDE and MGD, to compare them with those of healthy subjects, and to assess the impact of intense pulsed-light (IPL) therapy on the tear lipidome in MGD. METHODS: In a multicentre, prospective, observational-interventional case-control pilot study, 52 participants were enrolled in two phases: a discovery cohort (9 ADDE, 15 MGD, 13 controls) and an independent validation cohort (15 additional subjects). Tear lipids were profiled by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Unsupervised principal-component analysis (PCA) explored global variance; supervised partial least-squares discriminant analysis (PLS-DA) and orthogonal PLS-DA (OPLS-DA) defined group differences and yielded candidate biomarkers, with model robustness confirmed by permutation testing and CV-ANOVA. MGD participants received IPL at baseline, day 15, and day 45; clinical metrics and tear samples were obtained before and after therapy. RESULTS: A total of 176 lipid species were identified and quantified in positive- and negative-ion modes (ESI + and ESI-). Supervised PLS-DA clearly separated ADDE, MGD and control samples, while OPLS-DA highlighted 48 lipids that differed significantly among groups (p < 0.05). Both dry-eye subtypes were characterised by a pronounced depletion of lysophospholipids (LPE, LPC, LPG, LPI; fold change < 0.5) and an enrichment of (O-acyl)-ω-hydroxy fatty acids (OAHFA; fold change > 2) relative to controls. Cholesteryl esters (ChE) showed a subtype-specific elevation only in the MGD-versus-control comparison (fold change > 2). Permutation testing and CV-ANOVA confirmed the robustness of the ADDE-versus-MGD discrimination model. Although IPL therapy significantly improved clinical metrics such as tear break-up time and lissamine-green staining, the changes observed in the tear lipid profile were not statistically significant. CONCLUSIONS: Dry-eye subtypes appear to possess discrete lipidomic signatures; consequently, the lipid panel identified here could serve as a set of potential therapeutic targets. The dissociation between clinical improvement and lipidomic stability after IPL indicates that the therapy may benefit the ocular surface through mechanisms other than large-scale remodelling of the tear-film lipid layer, highlighting the need to explore complementary therapeutic pathways.
Management and safety of same day bilateral intravitreal anti-VEGF injections in a treat-and-extend regimen.
Plasencia C, Eschle J, Hatz K
BMC Ophthalmol · 2025 Aug · PMID 40814089 · Full text
BACKGROUND: Anti-vascular endothelial growth factor (VEGF) intravitreal injection treatment (IVT)s are gold standard for various neovascular retinal diseases, including neovascular age-related macular degeneration (nAMD)...
BACKGROUND: Anti-vascular endothelial growth factor (VEGF) intravitreal injection treatment (IVT)s are gold standard for various neovascular retinal diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and macular edema due to retinal vein occlusion (RVO). Same day bilateral IVTs are commonly performed off-label worldwide to reduce patient burden, despite limited safety data. This study evaluates the safety and management of bilateral same day anti-VEGF injections within a treat-and-extend regimen (TER) and proposes a clinical guideline for coordination of bilateral treatment. METHODS: This retrospective observational study analysed electronic health records of 428 included patients treated bilaterally with ranibizumab 0.5mg or aflibercept 2mg at the VISTA Augenklinik (Binningen, Switzerland) between 2015 and 2019. Patients included had bilateral macular edema due to nAMD, DME, or RVO and received at least two cycles of same day bilateral anti-VEGF injections within the TER. Treatment coordination followed one of four strategies: Equal TER, Coordinated TER, Mixed TER and pro re nata (PRN), and Asynchronous TER. Unilateral IVTs were also recorded during the same period in the same patient cohort. Ocular and systemic adverse events (AEs) were compared between unilateral and bilateral injections using Fisher's exact test. RESULTS: A total of 15,825 anti-VEGF injections were administered: 4,766 bilateral same day injections ([Formula: see text]) and 6,293 unilateral injections. Treatment intervals were synchronised according to visual acuity potential and disease activity. A treatment regime for bilateral IVTs has been established and is provided in the manuscript. The most frequently reported ocular AEs were conjunctival haemorrhage and sicca symptoms. Systemic AEs such as cerebrovascular and cardiovascular events were rare, with no significant difference between bilateral and unilateral injections. CONCLUSION: Bilateral same day intravitreal anti-VEGF injections within a TER regimen appear to be safe with no significant increase in ocular or systemic AEs compared to unilateral treatment. Coordinating bilateral IVTs using the clinical guideline presented in this study may reduce treatment visits, ease patient burden and improve compliance. Larger prospective studies are needed to confirm safety and support standardised guidelines for bilateral IVTs.
Noninvasive Synthesis of Multiframe Ultra-Widefield Fluorescein Angiography from Color Fundus Photographs.
Chen R, Xu K, Zheng K … +4 more , Zhang W, Lu Y, He M, Shi D
Ophthalmol Retina · 2026 Feb · PMID 40783110 · Publisher ↗
PURPOSE: To generate dye-free ultra-widefield fluorescein angiography (UWF-FA) images from noninvasive ultra-widefield color fundus photography (UWF-CFP) using generative artificial intelligence (AI) and to evaluate its...
PURPOSE: To generate dye-free ultra-widefield fluorescein angiography (UWF-FA) images from noninvasive ultra-widefield color fundus photography (UWF-CFP) using generative artificial intelligence (AI) and to evaluate its effectiveness in diabetic retinopathy (DR) screening. DESIGN: A cross-sectional study involving generative AI. PARTICIPANTS: This study included 1263 patients with DR (2747 UWF-CFP images and 18 321 UWF-FA images) from the Second People's Hospital of Foshan. METHODS: Ultra-widefield CFP and UWF-FA image pairs were matched and used to train a pix2pixHD generative adversarial network (GAN)-based model modified with Gradient Variance Loss. The generated UWF-FA images were evaluated using quantitative similarity metrics and qualitative ophthalmologist evaluation. An external data set, DeepDRiD, was used to validate the contribution of the generated UWF-FA images to DR grading. MAIN OUTCOME MEASURES: The area under the receiver operating characteristic curve for DR grading. RESULTS: The generated early-, mid-, and late-phase UWF-FA images demonstrated high authenticity, with multiscale similarity scores ranging from 0.70 to 0.91 and qualitative evaluation scores from 1.64 to 1.98 (1 = real UWF-FA quality). In a Turing test with 50 randomly selected images, 56% to 76% of the generated images were indistinguishable from real images. Generated UWF-FA images successfully depict details of DR lesions, such as a nonperfusion area and leakage. The incorporation of these generated UWF-FA images in DR grading significantly improved the area under the receiver operating characteristic curve from 0.869 to 0.904 compared with the baseline model using UWF-CFP images alone (P < 0.001). CONCLUSIONS: The study suggests that the GAN-based model can successfully generate realistic multiframe UWF-FA images, which could enhance DR grading without the need for IV dye injection, with the potential to improve the safety and accessibility of DR screening. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Intraocular Pressure Fluctuations Recorded by a Telemetric Sensor after Nonpenetrating Glaucoma Surgery in Primary Open-Angle Glaucoma.
Englisch CN, Trouvain AM, Wakili P … +7 more , Mansouri K, Burkhard Dick H, Hoffmann EM, Mackert MJ, Langenbucher A, Boden KT, Szurman P
Ophthalmol Glaucoma · 2026 · PMID 40714264 · Publisher ↗
OBJECTIVE: To investigate short- and long-term intraocular pressure (IOP) fluctuations in patients with primary open-angle glaucoma (POAG) after successful nonpenetrating glaucoma surgery (NPGS, canaloplasty or deep scle...
OBJECTIVE: To investigate short- and long-term intraocular pressure (IOP) fluctuations in patients with primary open-angle glaucoma (POAG) after successful nonpenetrating glaucoma surgery (NPGS, canaloplasty or deep sclerectomy). DESIGN: A prospective, open-label, multicenter interventional study. SUBJECTS: A total of 20 patients with POAG who underwent NPGS combined with permanent implantation of a suprachoroidal telemetric IOP sensor (EyeMate-SC, Implandata Ophthalmic Products GmbH). The mean age of the cohort was 66.9 ± 10.6 years. Half were female, and half were male. METHODS: Telemetric IOP measurements were obtained over a 3-year period, excluding the first 180 postoperative days and those during which ocular glaucoma medications were applied. One day was divided into 8 time-of-day (TOD) periods. The median absolute difference (MAD) in IOP between day χ and day χ + 7, 30, 90, 180, and 360 was calculated for each TOD and each eye, in which sequential IOP measurements were accordingly available. MAIN OUTCOME MEASURES: Intraocular pressure fluctuations. RESULTS: The mean follow-up duration was 952.8 ± 276.6 days. For analysis, a total of 139 512 mean IOP values were paired. Overall, diurnal IOP decreased by 20.7%, from 11.1 ± 5.0 mmHg in the "early morning" to 8.8 ± 3.2 mmHg in the "late evening," followed by a nocturnal IOP increase of 13.6% to 10.0 ± 3.8 mmHg in the "late night." Independently of the TOD, fluctuations were smallest during the 7-day interval and largest during the 360-day interval. The awake period, lasting from early morning to early evening, displayed increasing MADs with growing time intervals, resulting in moderate IOP fluctuations in the short term (1.5 mmHg < MAD < 2.0 mmHg) and large fluctuations in the long term (MAD > 2.0 mmHg). The late-night TOD displayed the lowest fluctuation amplitude. CONCLUSIONS: Nychthemeral IOP fluctuations persist in eyes with an average IOP of 10 mmHg after successful NPGS. Short-term IOP fluctuations were moderate, whereas long-term fluctuations were large. Irregular IOP measurements are insufficient to assess IOP fluctuation and thus to determine optimal glaucoma management. The implementation of safe and accurate telemetric sensors has the potential to enhance glaucoma management. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Dose-dependent myopia-suppressing effect of 4-phenlybutyric acid eye drops in a mouse myopia model under masked condition.
Ikeda SI, Sone K, Takai Y … +4 more , Miyano T, Negishi K, Tsubota K, Kurihara T
BMC Ophthalmol · 2025 Jul · PMID 40598091 · Full text
BACKGROUND: Myopia, characterized by excessive axial elongation of the eyeball, has become a significant global public health issue, particularly in Asia. Severe myopia increases the risk of ocular complications, includi...
BACKGROUND: Myopia, characterized by excessive axial elongation of the eyeball, has become a significant global public health issue, particularly in Asia. Severe myopia increases the risk of ocular complications, including retinal degeneration and glaucoma. Recent studies have identified the role of scleral extracellular matrix remodeling and endoplasmic reticulum (ER) stress in myopia pathogenesis. Our previous study identified scleral ER stress as a critical factor in myopia development. This study aimed to investigate the therapeutic potential of 4-phenylbutyric acid (4-PBA), a chemical chaperone, in mitigating scleral ER stress and its effects on myopia progression in a mouse myopia model under masked condition. METHODS: A lens-induced myopia (LIM) mouse model was utilized to evaluate the effects of 4-PBA administered as eye drops. Mice received varying concentrations of 4-PBA or phosphate-buffered saline (PBS) as a control. Changes in refractive error and axial length were measured to assess myopia progression. In addition, further experiments were also conducted under masked conditions, where the experimenter was unaware of the treatment was being applied, for the three conditions of 2%, 0.5% 4-PBA eye drops or vehicle treatment of LIM mice. RESULTS: Administration of 4-PBA at concentrations of 0.5% and higher significantly suppressed the myopic shift in refraction and axial elongation associated with myopia compared to mice in the PBS control group. In a blinded, masked experiment, 2% and 0.5% 4-PBA eye drops also suppressed the progression of myopia in a dose-dependent manner. CONCLUSIONS: This study demonstrated that 4-PBA effectively mitigated myopia progression in a mouse model by targeting scleral ER stress. The dose-dependent suppression of myopic shifts and axial elongation under masked experimental condtion highlights the potential of 4-PBA as a therapeutic agent for managing myopia. These findings pave the way for further research and potential clinical applications in myopia treatment.
The five-step medial epicanthoplasty: simple and standardized.
Chen J, Zhang J, Xi W … +2 more , Chen W, Yang F
BMC Ophthalmol · 2025 May · PMID 40375074 · Full text
BACKGROUND: Epicanthus refers to the longitudinal curved skin folds that cover the medial canthus, which affect aesthetics due to covering the medial canthus angle and lacrimal mound. Various surgical methods exist for c...
BACKGROUND: Epicanthus refers to the longitudinal curved skin folds that cover the medial canthus, which affect aesthetics due to covering the medial canthus angle and lacrimal mound. Various surgical methods exist for correcting epicanthus, each with its own set of advantages and disadvantages, and lacking a standardized operational protocol, making it difficult for beginners to master and for clinical promotion.This article aims to explore a standardized and simplified five-step procedure for treating epicanthus and report our clinical experience and effectiveness. METHODS: A retrospective analysis was conducted from October 2019 to September 2022 at the Burn and Plastic Surgery Department of the Second Affiliated Hospital of South China University. A consistent team of doctors utilized a five-step method to correct the medial canthus in 306 patients with epicanthus. All patients were followed up for more than 6 months. We observed 306 patients and used iris diameter as a reference value to subjectively evaluate the clinical effect through photo evaluation and scar scoring.Objective evaluation of clinical efficacy was achieved through the inter canthal distance (ICD) and palpebral fissure length (PFL). RESULTS: The study included 295 females and 11 males, with an average follow-up time of 14.2 months.The average increase rate of PFL is 14.9%, and the average reduction rate of ICD is 8.6%. Two cases of bleeding and swelling were promptly treated, and no long-term complications were left. 85 cases of scar hyperplasia were treated with KELO-COTE® silicone gel, triamcinolone injection, and appropriate laser therapy in combination, and the scars gradually resolved after 12 months. 4 cases of recurrence and 2 cases of asymmetry underwent reoperation. Observing the satisfaction and effectiveness rate of 306 patients, the overall satisfaction and effectiveness rate reached over 95%. About 96.40% of patients were satisfied with the surgery and would recommend it to their family and friends. The paired t-test was used for statistical analysis, and the results showed statistical significance. CONCLUSIONS: The five-step method for correcting epicanthus proves to be a simple, efficient, and reliable technique that is easily mastered by beginners. It boasts high patient satisfaction and carries a low risk of scar formation.
Risk factors for pupil changes in patients with diabetic retinopathy and cataract after phacoemulsification with intraocular lens implantation.
Yi G, Yu H
BMC Ophthalmol · 2025 Apr · PMID 40295992 · Full text
BACKGROUND: This study aims to identify the risk factors associated with pupillary changes in patients with diabetic retinopathy (DR) and cataract undergoing phacoemulsification with intraocular lens implantation (PHACO ...
BACKGROUND: This study aims to identify the risk factors associated with pupillary changes in patients with diabetic retinopathy (DR) and cataract undergoing phacoemulsification with intraocular lens implantation (PHACO + IOL). METHODS: This retrospective observational study included patients with DR and cataract who underwent phacoemulsification and intraocular lens implantation between February 2021 and August 2023. Patients were categorized into two groups based on the presence or absence of pupillary changes following surgery. RESULTS: A total of 162 patients were analyzed, with pupillary changes occurring in 33 cases (20.37%). Multivariate logistic regression analysis revealed that a longer duration of diabetes (OR = 2.73; 95% CI: 1.02-7.27, P = 0.045), higher lens nucleus grade (OR = 3.95; 95% CI: 1.58-9.89, P = 0.003), greater severity of DR (OR = 3.60; 95% CI: 1.40-9.28, P = 0.008), and intraoperative posterior lens capsule rupture (OR = 6.41; 95% CI: 1.75-23.47, P = 0.005) were significant risk factors for postoperative pupillary changes in DR patients undergoing PHACO + IOL. CONCLUSION: Phacoemulsification with intraocular lens implantation is an effective treatment for patients with DR and cataract. However, factors such as the duration of diabetes, severity of DR, and intraoperative complications are associated with an increased risk of pupillary changes. Therefore, rigorous blood glucose control, adherence to standardized surgical protocols, and preventive care are recommended to optimize patient outcomes. TRIAL REGISTRATION: Not applicable. CLINICAL TRIAL NUMBER: Not applicable.
Quorum-Sensing inhibition by furanone compounds and therapeutic effects on Pseudomonas aeruginosa keratitis rabbit model.
Dal A, Hekimoğlu R, Sümbül B … +4 more , Balıbey FB, Gökçe ZÖ, Akbulut E, Elbay A
BMC Ophthalmol · 2025 Apr · PMID 40264027 · Full text
BACKGROUND: To investigate Quorum-Sensing inhibition by furanone compounds in Pseudomonas aeruginosa keratitis rabbit model. METHODS: Thirty adult New Zealand White rabbits were used. Anesthetized rabbits were intrastrom...
BACKGROUND: To investigate Quorum-Sensing inhibition by furanone compounds in Pseudomonas aeruginosa keratitis rabbit model. METHODS: Thirty adult New Zealand White rabbits were used. Anesthetized rabbits were intrastromally injected with Pseudomonas aeruginosa (P. aeruginosa). The rabbits were divided into six groups: the control group (infected only with P. aeruginosa), group A (50 mg/mL ceftazidime), group B (0.1 mg/mL furanone), group C (0.2 mg/mL furanone), group D (0.3 mg/mL furanone), and group E (20% dimethyl sulfoxide). One drop of the treatment was applied every hour for 3 days, starting 1-h post-inoculation. Rabbits were then sacrificed, and corneas were analysed clinically, microbiologically, histologically, and biochemically. One-way analysis of variance was used for the mean comparison of independent groups. The Least Significant Difference method was used as a post-hoc test for pairwise comparisons. RESULTS: In all evaluations, the antibiotic group (group A) showed the best therapeutic response. The slit-lamp examination score of group C was significantly lowered than those compared of to the control (p = 0.009) and E groups (p = 0.014). Histological evaluation showed that inflammation is decreased in groups B, C, and D. Levels of cyclooxygenase-2 (COX-2), superoxide dismutase-1, and reactive oxygen species (ROS) were lowest in the antibiotic-treated group, whereas the highest levels were detected in the control group. Notably, the COX-2 levels in group B and ROS levels in groups B and C were significantly lower than in control group. (p = 0.045, p = 0.039 and p = 0.045, respectively). CONCLUSION: Furanone compounds may have minimal therapeutic effects against Pseudomonas keratitis. Its therapeutic effect has not been observed to be sufficient compared with that of antibiotics. Further studies are needed to investigate their protective effects and mechanisms.
Changes in aqueous humor cytokines and metabolomics in contralateral eye after unilateral cataract surgery.
Li Y, Cheng T, Zhou S … +4 more , Li F, Guo W, Li M, Liu T
BMC Ophthalmol · 2025 Mar · PMID 40098128 · Full text
BACKGROUND: For patients with bilateral age-related cataracts, sequential phacoemulsification and intraocular lens implantation is a common treatment. However, it remains unclear whether surgery on the first eye has an i...
BACKGROUND: For patients with bilateral age-related cataracts, sequential phacoemulsification and intraocular lens implantation is a common treatment. However, it remains unclear whether surgery on the first eye has an impact on the second eye, as current research results are inconsistent. This study will explore whether surgery on one eye affects the non-operated eye through aqueous humor cytokines and metabolomic analyses in the second eye. METHODS: A rabbit model of unilateral phacoemulsification and intraocular lens implantation was established. The experimental group consisted of 15 rabbits undergoing this procedure. Postoperatively, rabbits were divided into five subgroups (three rabbits per subgroup), and aqueous humor was collected from both the operated and non-operated eyes at 1 day, 3 days, 1 week, 2 weeks, and 3 weeks after surgery. Additionally, 5 rabbits were selected as a control group, from which aqueous humor was extracted. Levels of IL-1a, IL-1β, IL-2, IL-4, IL-6, IL-8, IFN-γ, TNF-α, MCP-1, and VEGF in the aqueous humor were compared. In the clinical study, preoperative aqueous humor samples were collected from 22 patients undergoing bilateral phacoemulsification and intraocular lens implantation. Among them, 11 patients were tested for the aforementioned 10 cytokines, while the other 11 patients underwent untargeted metabolomics research. RESULTS: In the animal experiment, levels of all 10 cytokines in the operated eyes were significantly higher compared to both the control and non-operated eyes groups (P < 0.05). In the non-operated eyes, IL-1β and IL-2 levels were also elevated compared to the control (P < 0.05); however, no statistically significant differences were observed between the non-operated eyes and the control group at postoperative time points of 1 day, 3 days, 1 week, 2 weeks, and 3 weeks. In the clinical study, no significant differences were found in cytokine levels between the two eyes. In the untargeted metabolomics analysis, 354 metabolites showed differential expression, 280 were upregulated and 74 were downregulated. Notably, Adenine and 2-Aminopurine were significantly downregulated, highlighting Purine metabolism as the most impacted pathway. CONCLUSIONS: Animal experiments showed a significant increase in IL-1β and IL-2 levels in the non-operated eyes postoperatively, reflecting systemic and local inflammatory responses. In clinical experiments, although no significant changes in cytokines were observed in the aqueous humor of both eyes, differential expression of metabolites indicated metabolic adjustments in the non-operated eye following surgery on the first eye. These findings reveal that unilateral cataract surgery may affect the stability of the intraocular environment in the contralateral eye, suggesting that in staged bilateral surgeries, potential metabolic changes in the non-operated eye and their clinical significance should be considered. This result provides important reference value for optimizing postoperative management strategies, reducing complications, and determining the timing for bilateral surgeries, warranting further investigation.
Change in monochromatic aberrations with accommodation in a large adult population.
Mechó-García M, Arcas-Carbonell M, Orduna-Hospital E … +6 more , Sánchez-Cano A, Fernández-Sánchez V, Macedo-de-Araújo RJ, Fernandes P, González-Méijome JM, Rozema JJ
BMC Ophthalmol · 2025 Mar · PMID 40033260 · Full text
BACKGROUND: During accommodation, the eye undergoes significant structural changes, altering wavefront aberrations. So, this study aimed to evaluate changes in Zernike coefficients up to the 6th order with different acco...
BACKGROUND: During accommodation, the eye undergoes significant structural changes, altering wavefront aberrations. So, this study aimed to evaluate changes in Zernike coefficients up to the 6th order with different accommodation demands and ages in a large cohort of young adults, considering the decrease in pupil size with the accommodation. METHODS: Aberrometric measurements for 210 healthy subjects aged 18-40 were performed with the irx3 (Imagine Eyes, Orsay, France), stimulating accommodation with the Badal system of the instrument, from 0 to 5 D. Each wavefront was rescaled to a standardized pupil size for each accommodative vergence. Variations of Zernike coefficients were analyzed for each accommodative demand, and the change of Zernike coefficients with age. RESULTS: The most notable changes observed during accommodation was the increase in C(2,0). Both C(2,±2) astigmatism showed a reduction in magnitude during accommodation. C(4,0) became less positive, or more negative, as accommodation increased. C(3,-1) remained constant as the accommodation demand increased, while C(3,1) showed an increase. Changes were observed with accommodation and age, where C(2,0) had a negative linear relationship. The C(4,0) changed gradually with age only for accommodative demands below 3 D. C(3,±1) decreased with age. CONCLUSIONS: Wavefront aberration coefficients presented changes during accommodation in people aged 20-40 years. C(2,0) underwent the most pronounced changes and C(4,0) changed more with accommodation than other higher-order aberrations. Zernike coefficients C(2,0), C(4,0) and C(3,±1) decreased with age, and C(2,±2) astigmatisms showed an increase in magnitude with age. These findings were made considering the decrease in pupil size with accommodation, highlighting the importance of accounting for pupil diameter variations when evaluating wavefront aberrations.
Cataract and Risk of Fracture: A Systematic Review, Meta-Analysis, and Bayesian Network Meta-Analysis.
Gallo Afflitto G, Aiello F, Surico PL … +5 more , Malek DA, Mori T, Swaminathan SS, Maurino V, Nucci C
Ophthalmology · 2025 Aug · PMID 39978438 · Publisher ↗
TOPIC: To evaluate the odds ratio (OR) and hazard ratio (HR) of bone fracture in phakic subjects with cataract compared with phakic subjects without cataract and pseudophakic individuals. CLINICAL RELEVANCE: Despite the...
TOPIC: To evaluate the odds ratio (OR) and hazard ratio (HR) of bone fracture in phakic subjects with cataract compared with phakic subjects without cataract and pseudophakic individuals. CLINICAL RELEVANCE: Despite the growing recognition of the link between cataract and fracture, the available evidence remains inconclusive. METHODS: The results of this meta-analysis were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study protocol was registered on the International Prospective Register of Systematic Reviews (ID: CRD42024587477). Four electronic databases were searched from their inception to May 2024: PubMed, Embase, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Two reviewers performed title and abstract screening, full-text assessment, and study quality appraisal. Frequentist inference meta-analysis and Bayesian network meta-analyses (NMAs) were conducted to assess the OR and HR of fracture among the 3 groups of interest. RESULTS: Sixteen articles met the predefined inclusion and exclusion criteria, with the 11 included in the quantitative synthesis encompassing a population of 4 713 458 subjects and reporting on 284 811 fractures. The certainty of evidence was rated from low to moderate. Compared with subjects without cataract, the OR and the HR for fractures in the cataract group were 1.44 (95% confidence interval [CI]: 0.75-2.75; P > 0.05) and 1.51 (95% CI: 1.14-2.01; P = 0.0152), respectively. Bayesian NMAs indicated that subjects with cataracts have an increased OR and HR of fractures compared with both phakic subjects without cataracts (OR: 3.0 [95% credible interval [CrI]: 2.8-3.3]; HR 1.1 [95% CrI: 1.09-1.12]) and pseudophakic individuals (OR: 1.7 [95% CrI: 1.6-1.8]; HR: 1.28 [95% CrI: 1.24-1.31]). Pseudophakic individuals exhibit a 27% reduction in fracture risk compared with phakic individuals with cataracts, with 1 less fracture event for every 8 pseudophakic subjects. CONCLUSION: Low-certainty evidence suggests a higher fracture risk in individuals with cataract compared with those without. Moderate-certainty evidence indicates that pseudophakic individuals have the lowest fracture risk compared with phakic patients with or without cataract. Further research should explore the causal link between cataract and fracture risk and evaluate the impact of cataract surgery on fracture prevention. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Internal Limiting Membrane Flaps in Macular Hole Surgery: A Systematic Review and Individual Participant Data Meta-analysis.
Tzoumas N, McNally TW, Teh BL … +6 more , Zaman M, Yorston D, Lois N, Chaudhary V, Steel DH, ILM Flap Study Group
Ophthalmol Retina · 2025 Aug · PMID 39923898 · Publisher ↗
TOPIC: To compare anatomic and visual outcomes of internal limiting membrane (ILM) flaps versus peeling in macular hole surgery, considering hole size, symptom duration, and different flap types. CLINICAL RELEVANCE: The...
TOPIC: To compare anatomic and visual outcomes of internal limiting membrane (ILM) flaps versus peeling in macular hole surgery, considering hole size, symptom duration, and different flap types. CLINICAL RELEVANCE: The benefit of ILM flaps over standard ILM peeling in idiopathic full-thickness macular holes (iFTMHs) remains unclear. METHODS: Registered systematic review and individual participant data (IPD) meta-analysis of randomized controlled trials comparing conventional ILM peeling with ILM flaps in adults undergoing primary iFTMH surgery (CRD42023494971). No exclusions based on hole size, symptom duration, or perioperative choices. Searches in MEDLINE, Embase, Cochrane Library, and trial registries. Critical outcomes were hole closure and postoperative visual acuity at 6 months or nearest time point. Regression models adjusted for age, sex, hole size, lens status, and preoperative visual acuity, allowing for nonlinear effects. Evidence was appraised with Cochrane Risk of Bias, Grading of Recommendations Assessment, Development, and Evaluations, and the Instrument to assess the Credibility of Effect Modification in Analyses. Subgroup analyses considered hole size, symptom duration, flap subtypes, tamponade choice, and risk-of-bias. RESULTS: Thirteen trials provided IPD for 792 eyes. Most (68.3%) had minimum linear diameter ≥500 μm, with limited representation of holes <400 and ≥900 μm. The adjusted odds ratio (OR) for primary closure with ILM flap versus peeling was 4.80 (95% confidence interval, 2.77-8.30; P < 0.001), with a relative risk of 1.26 (1.20-1.30) (Grading of Recommendations Assessment, Development, and Evaluations: moderate-certainty), and a number needed to treat of 6. Compared with peeling, the ILM flap group showed better postoperative visual acuity at 3 to 6 months, with a mean difference (MD) of -0.14 logarithm of the minimum angle of resolution (-0.18 to -0.09; P < 0.001), about 7 letters ETDRS (Grading of Recommendations Assessment, Development, and Evaluations: moderate-certainty). Internal limiting membrane flaps were likely more beneficial for holes ≥500 μm (OR for closure: 3.14-9.64, P < 0.001; MD in vision: -0.23 to -0.13, P < 0.001). Nonlinear analyses suggested probable benefits across a broader range of hole sizes (Instrument to assess the Credibility of Effect Modification in Analyses: moderate-confidence). Results were consistent across risk-of-bias assessments, with no significant differences between ILM flap techniques. CONCLUSION: Internal limiting membrane flaps likely improve closure and visual recovery compared with peeling alone in iFTMH, with greater effects likely in holes >500 μm. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
The effect of low vision rehabilitation on the quality of life and caregiver burden of low vision patients - a randomized trial.
Cai C, Shuai Y, Li G
BMC Ophthalmol · 2025 Jan · PMID 39815249 · Full text
BACKGROUND: The quality of life for low vision patients is a comprehensive concept that involves multiple aspects, including physical, psychological, and social aspects. Visual impairment is an important factor in the de...
BACKGROUND: The quality of life for low vision patients is a comprehensive concept that involves multiple aspects, including physical, psychological, and social aspects. Visual impairment is an important factor in the decline of patients' quality of life. The purpose of this study is to investigate the impact and feasibility of carrying out low vision rehabilitation nursing on the quality of life and nursing burden of low vision patients. METHODS: Select 18 low vision patients who received treatment at a tertiary ophthalmic hospital in Shantou City and randomly divide them into an experimental group and a control group. The control group received routine low vision health education, while the experimental group received intervention measures based on low vision rehabilitation nursing plans. A questionnaire survey was conducted on two groups of study subjects and their caregivers using the Low Vision Quality of Life Questionnaire, General Self-Efficacy Scale, and Zarit Burden Interview before intervention, at week 4 after intervention, and at week 8 after intervention. The scores of each scale in the experimental group and the control group were statistically analyzed. RESULT: The quality of life and self-efficacy scores of the experimental group patients were higher than those of the control group in the 4th and 8th week after intervention; The caregiver burden of the experimental group patients was lower than that of the control group caregivers in the 4th and 8th weeks after intervention. CONCLUSION: Implement a low vision rehabilitation nursing plan, provide rehabilitation intervention and support to low vision patients, help patients find new ways to adapt to low vision conditions, and improve their quality of life. Low vision rehabilitation nursing interventions not only enable patients to regain the ability to independently complete daily activities, but also improve their self-efficacy, help rebuild confidence, and reduce the caregiving burden on their caregivers.
Prophylactic barrage laser in patients with previous vitreous loss during cataract surgery: a randomized clinical trial.
Namvar E, Abuali M, Setoodehmanesh MA … +1 more , Moalem M
BMC Ophthalmol · 2025 Jan · PMID 39762825 · Full text
BACKGROUND: One of the significant challenges that can arise during cataract surgery is the occurrence of posterior capsule rupture (PCR) and vitreous loss. It may result in different complications including cystoid macu...
BACKGROUND: One of the significant challenges that can arise during cataract surgery is the occurrence of posterior capsule rupture (PCR) and vitreous loss. It may result in different complications including cystoid macular edema, endophthalmitis, glaucoma, and considerably retinal detachment which consequently contributes to poor functional outcomes. METHODS: This study was a prospective double blinded randomized clinical trial including 42 patients with previous complicated cataract surgery including posterior capsular rupture and consequently vitreous loss that anterior vitrectomy was done for them. The patients were randomly categorized in to two groups by simple randomization. One group (25 patients) received sham laser and the other group (17 patients) received prophylactic 360° barrage laser 4 weeks after cataract surgery. After eighteen months, rate of retinal detachment was compared between two groups. RESULTS: In terms of gender, age, axial length, maturity, pseudophakia v/s aphakia, type of IOL and type of cataract surgery, there was no statistically significant difference between intervention and control groups. Distribution of RRD was clinically different between 2 groups (intervention and control group). In addition, there was a statistically significant difference between the rate of RRD in control group (non-laser patients) and normal population (0.08 vs. 0.0001). (P-value < 0.001). CONCLUSION: Prophylactic barrage laser might be a useful intervention in eyes with posterior capsule rupture and vitreous loss during cataract surgery to prevent rhegmatogenous retinal detachment. However, further studies with larger sample sizes are indicated. TRIAL REGISTRATION: Iranian Clinical Trial Registry: IRCT20201120049450N2, Registered 13 Jul 2023, https://irct.behdasht.gov.ir .
Intraocular complement activation is independent of systemic complement activation and is related to macular vascular remodelling in retinal vein occlusion.
Liu H, Zhou Y, Qi J … +7 more , Liang S, Guo T, Chen J, Tan H, Wang J, Xu H, Chen Z
BMC Ophthalmol · 2024 Nov · PMID 39587546 · Full text
BACKGROUND: Retinal vein occlusion (RVO) is a major cause of vision loss. The pathogenesis remains poorly defined although inflammation is known to play a critical role. In this study, we investigated the levels of compl...
BACKGROUND: Retinal vein occlusion (RVO) is a major cause of vision loss. The pathogenesis remains poorly defined although inflammation is known to play a critical role. In this study, we investigated the levels of complement proteins in the aqueous humour and plasma of RVO participants and the relationship between complement levels and retinal pathologies. METHODS: The plasma and aqueous humour were collected from 20 treatment-naive RVO and 20 cataract patients. Retinal lesions were examined by fundus stereoscopy and optical coherence tomography angiography. The levels of C1q, C2, C4, C4b, C3, C3b/iC3b, C5, C5a, CFB, CFD, CFI, CFH, and MBL in the plasma and aqueous humour were measured using the Luminex x MAP multiplex assay. RESULTS: RVO patients had significantly higher levels of C4, C4b, C3b/iC3b, CFB, and CFH in the plasma and aqueous humour compared to controls. The aqueous levels of C1q, C2, C5, C5a, and MBL were also significantly higher in RVO patients than in controls. CRVO patients had higher intraocular levels of C1q, C4, C5, CFI, CFH, and MBL than BRVO patients. C5a was below the detectable limit in the plasma in 18 cataracts and 16 RVO participants. The intraocular levels of C5a positively correlated with C1q, C2, C4, C3, C5, CFB, CFH, and MBL. The intraocular levels of CFD, CFI and MBL positively correlated with CRT, and the levels of C2, C3, C5, CFB, and MBL negatively correlated with the size of the foveal avascular zone. The plasma levels of C4b, C3b/iC3b, and CFD positively correlated with their counterparts in the aqueous humour in cataracts but not in RVO patients. The ratios of aqueous humour/plasma of C1q, C4, C4b, C3b/iC3b, C5, CFB, CFD, CFI, and CFH in the RVO patients were significantly higher than those in the cataract patients. DISCUSSION AND CONCLUSIONS: The intraocular complement activation in RVO is mediated by the classical and the alternative pathways and is largely independent of systemic complement activation. Intraocular complement activation may be related to retinal oedema and vascular remodeling in RVO patients.
Effect of defocus incorporated multiple segments (DIMS) spectacle lenses on myopia progression in children: a retrospective analysis in a German real-life clinical setting.
Neller B, Neller K, Schwahn H … +5 more , Mattern AI, Devenijn M, Langenbucher A, Seitz B, Kaymak H
BMC Ophthalmol · 2024 Sep · PMID 39266992 · Full text
OBJECTIVES: This retrospective analysis evaluates the treatment success of "Defocus Incorporated Multiple Segments" (DIMS) spectacle lenses in a real-life clinical setting in Germany. MATERIALS AND METHODS: Axial length...
OBJECTIVES: This retrospective analysis evaluates the treatment success of "Defocus Incorporated Multiple Segments" (DIMS) spectacle lenses in a real-life clinical setting in Germany. MATERIALS AND METHODS: Axial length (AL) and objective refraction of 166 eyes treated with DIMS at baseline and 12-month follow-up were analyzed. Annual AL growth rate within the range of physiological growth rate was considered a successful treatment. Myopia progression of ≥ -0.5 D/yr accounted as treatment success. Differences in percentages of treatment success of subgroups depending on baseline AL and age against treatment success of the total population were investigated. RESULTS: Considering all eyes, treatment success regarding AL growth and myopia progression was achieved in 46% and 65%, respectively. Male eyes with moderate AL showed treatment success in a higher proportion (73%, p < 0.01; 89%, p < 0.01); eyes with high AL showed treatment success in a lower proportion (25%, p < 0.01; 51%, n.s.). Female eyes showed the same trend but without statistical significance (moderate AL: 49%; 68%; high AL: 40%; 62%). Younger children showed treatment success in a lower proportion (male: 11%, p < 0.01; 38%, p < 0.05; female: 25%, p < 0.01; 42%, p < 0.01). Older children showed treatment success in a higher proportion (male: 60%, p < 0.05; 78% p < 0.05; female: 53%, n.s.; 77% p < 0.05). CONCLUSIONS: Eyes with moderate baseline AL and of older children showed treatment success after 12 months of DIMS treatment. Eyes with a high baseline AL and of younger children showed treatment success in a smaller proportion, therefore combination treatment should be considered. In future studies, males and females should be assessed separately.
Perspectives on the Incidence of Acanthamoeba Keratitis: A Systematic Review and Meta-Analysis.
Aiello F, Gallo Afflitto G, Ceccarelli F … +5 more , Turco MV, Han Y, Amescua G, Dart JK, Nucci C
Ophthalmology · 2025 Feb · PMID 39127408 · Publisher ↗
TOPIC: To provide an overview on the incidence of Acanthamoeba keratitis (AK). CLINICAL RELEVANCE: Although being a sight-threatening cause of infectious keratitis, a comprehensive assessment of the incidence of AK is la...
TOPIC: To provide an overview on the incidence of Acanthamoeba keratitis (AK). CLINICAL RELEVANCE: Although being a sight-threatening cause of infectious keratitis, a comprehensive assessment of the incidence of AK is lacking. METHODS: Incidence of AK was computed as the number of eyes with AK per health care center, per year (annualized center incidence [ACI]). Two meta-analytical ratios also were calculated: (1) the ratio of eyes with AK to the count of eyes with nonviral microbial keratitis (MK) and (2) the ratio of eyes with AK to the overall population (i.e., the total number of people in a nation or region, as indicated by the authors in each study). Center was defined as the health care facility where the study took place. Actual and projected estimates of the number of eyes with AK in years were calculated multiplying the ratio of eyes with AK to the total population and the corresponding population estimates, sourced from the United Nations Population Prospects. RESULTS: Overall, 105 articles were included, published between 1987 and 2022. The total number of eyes identified was 91 951, with 5660 eyes affected by AK and 86 291 eyes affected by nonviral MK. The median ACI was 1.9 eyes with AK per health care center per year (95% confidence interval [CI], 1.5-2.6 eyes), with no statistically significant differences among continents. The ratio of eyes with AK to the total number of eyes with MK was 1.52% (95% CI, 1.03%-2.22%), whereas the ratio of eyes with AK in relationship to the entire population was estimated at 2.34 eyes per 1 000 000 people (95% CI, 0.98-5.55 per 1 000 000 people). The projected increase in the numbers of eyes with AK indicated an increase of 18.5% (n = 15 355 eyes with AK) in 2053 and 25.5% (n = 16 253 eyes with AK) in 2073, compared with the baseline of 2023 (n = 12 953 eyes with AK). DISCUSSION: Acanthamoeba keratitis emerged as a relatively low-incident disorder, and no significant differences in terms of its incidence were found among different continents. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Efficacy and Safety of 0.19-mg Fluocinolone Acetonide Implant in Postoperative Cystoid Macular Edema after Pars Plana Vitrectomy: The ILUvien in Postoperative CYstoid Macular eDema Study.
Motloch K, Soler V, Delyfer MN … +13 more , Vasseur V, Wolff B, Issa M, Dot C, Massé H, Weber M, Comet A, Hitzl W, Matonti F, Creuzot-Garcher C, Tadayoni R, Kodjikian L, Couturier A
Ophthalmol Retina · 2024 Dec · PMID 39004282 · Publisher ↗
PURPOSE: To assess the efficacy and safety of 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (Iluvien) in treating chronic postoperative cystoid macular edema (PCME) after pars plana vitrectomy. DESIGN: Retros...
PURPOSE: To assess the efficacy and safety of 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (Iluvien) in treating chronic postoperative cystoid macular edema (PCME) after pars plana vitrectomy. DESIGN: Retrospective multicentric case series in clinical settings. SUBJECTS: Patients with chronic PCME who underwent vitrectomy in tertiary care centers in France. METHODS: Review of charts and OCT scans. MAIN OUTCOME MEASURES: The primary end points were the best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Secondary end points were the intraocular pressure (IOP); proportion of patients maintaining a BCVA ≥20/40; need for additional nonstudy treatment; differences between eyes that underwent a single and multiple surgeries; and OCT biomarkers of better BCVA. RESULTS: Forty-nine eyes of 49 patients with a mean follow-up of 24.5 ± 3.87 months were included. The mean BCVA increased from 0.40 ± 0.26 logarithm of the minimum angle of resolution (logMAR) at baseline to 0.32 ± 0.24 logMAR at month 24 (P = 0.0035). The mean CRT decreased from 409 ± 139 μm at baseline to 340 ± 92 μm at month 24 (P = 0.0001). The mean IOP was 14.0 ± 4 mmHg at baseline and remained stable at 14.03 ± 4.1 mmHg at month 24 (P = 0.99). During the follow-up, the IOP exceeded 21 mmHg in 9 eyes, with one eye requiring cyclophotocoagulation. The BCVA was ≥20/40 in 47% of eyes (95% confidence interval [CI], 34%-61%) at baseline and in 58% of eyes at month 24 (95% CI, 41%-73%). At month 18, the likelihood of achieving a BCVA ≥20/40 was higher in eyes with intact external limiting membrane and ellipsoid zone. Additional dexamethasone (DEX) implant was injected in 14 eyes (28.6%). The treatment burden of 2.45 ± 1.35 DEX implant/y was decreased to 0.57 ± 0.60 DEX implant/y after FAc implantation (P = 0.001). CONCLUSIONS: Fluocinolone acetonide implant improved the BCVA, reduced the CRT, and allowed reducing treatment burden in eyes with chronic PCME after vitrectomy. The safety profile was acceptable. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Refractive Outcomes Following Combined Cataract and Microinvasive Glaucoma Surgery.
Shaheen A, Afflitto GG, Swaminathan SS
Ophthalmol Glaucoma · 2024 · PMID 39004220 · Full text
PURPOSE: To compare refractive outcomes in eyes undergoing cataract extraction (CE) alone, CE with goniotomy (CE/goniotomy), and CE with Schlemm's canal stent (CE/SCS) insertion. DESIGN: Retrospective cohort study. PARTI...
PURPOSE: To compare refractive outcomes in eyes undergoing cataract extraction (CE) alone, CE with goniotomy (CE/goniotomy), and CE with Schlemm's canal stent (CE/SCS) insertion. DESIGN: Retrospective cohort study. PARTICIPANTS: Eyes from the Bascom Palmer Glaucoma Repository undergoing CE/goniotomy, CE/SCS insertion, or uncomplicated CE alone between July 2014 and February 2022 were identified. METHODS: Refraction data were analyzed at postoperative month (POM) 1 and 6 with Kruskal-Wallis and Dunn's tests. Anisometropia was defined as a spherical equivalent (SE) difference of ≥2D. MAIN OUTCOME MEASURES: The primary outcome was mean refraction at POM1 and POM6 across the 3 surgical groups. Secondary outcomes were comparisons of refraction and visual acuity (VA) among different goniotomy and Schlemm's canal stent (SCS) devices, as well as incidence of anisometropia. RESULTS: A total of 8360 eyes (150 CE/goniotomy, 395 CE/SCS, and 7815 CE alone) from 6059 patients were analyzed. At POM1, mean SE in the CE/goniotomy, CE/SCS, and CE alone groups was -0.36 ± 0.91D, -0.31 ± 0.85D, and -0.39 ± 0.88D respectively (P = 0.019). Mean logarithm of the minimum angle of resolution VA was 0.10 ± 0.20, 0.08 ± 0.19, and 0.14 ± 0.26 respectively (P = 0.002, CE/SCS vs. CE alone). No statistically significant differences were noted at POM6. Anisometropia occurred at POM1 in 2 patients (13.3%) in the CE/goniotomy-CE group, 1 patient (3.2%) in the CE/SCS-CE group, and 184 patients (4.9%) in the CE-CE group (P = 0.217). At POM6, mean SEs were -0.38 ± 0.97D (CE/goniotomy), -0.35 ± 0.81D (CE/SCS), and -0.40 ± 0.91D (CE alone; P = 0.473). No significant differences in overall refractive outcomes were observed with different SCS or goniotomy devices. Among primary open-angle glaucoma/normal-tension glaucoma eyes, mean SE at POM1 was -0.36 ± 0.73D (CE/goniotomy), -0.24 ± 0.84D (CE/SCS), and -0.45 ± 0.81D (CE alone; P < 0.001). CONCLUSIONS: Concurrent SCS insertion or goniotomy with CE was associated with some statistically significant differences in postoperative refraction and VA, although these small magnitude differences were unlikely to be clinically meaningful. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references in the Footnotes and Disclosures at the end of this article.
Plasma Metabolomics Identifies Key Metabolites and Improves Prediction of Diabetic Retinopathy: Development and Validation across Multinational Cohorts.
Yang S, Liu R, Xin Z … +9 more , Zhu Z, Chu J, Zhong P, Zhu Z, Shang X, Huang W, Zhang L, He M, Wang W
Ophthalmology · 2024 Dec · PMID 38972358 · Publisher ↗
PURPOSE: To identify longitudinal metabolomic fingerprints of diabetic retinopathy (DR) and to evaluate their usefulness in predicting DR development and progression. DESIGN: Multicenter, multiethnic cohort study. PARTIC...
PURPOSE: To identify longitudinal metabolomic fingerprints of diabetic retinopathy (DR) and to evaluate their usefulness in predicting DR development and progression. DESIGN: Multicenter, multiethnic cohort study. PARTICIPANTS: This study included 17 675 participants from the UK Biobank (UKB) who had baseline prediabetes or diabetes, identified in accordance with the 2021 American Diabetes Association guidelines, and were free of baseline DR and an additional 638 participants with type 2 diabetes mellitus from the Guangzhou Diabetic Eye Study (GDES) for external validation. Diabetic retinopathy was determined by ICD-10 codes in the UKB cohort and revised ETDRS grading criteria in the GDES cohort. METHODS: Longitudinal DR metabolomic fingerprints were identified through nuclear magnetic resonance (NMR) assay in UKB participants. The predictive value of these fingerprints for predicting DR development were assessed in a fully withheld test set. External validation and extrapolation analyses of DR progression and microvascular damage were conducted in the GDES cohort using NMR technology. Model assessments included the concordance (C) statistic, net classification improvement (NRI), integrated discrimination improvement (IDI), calibration, and clinical usefulness in both cohorts. MAIN OUTCOME MEASURES: DR development and progression and retinal microvascular damage. RESULTS: Of 168 metabolites, 118 were identified as candidate metabolomic fingerprints for future DR development. These fingerprints significantly improved the predictability for DR development beyond traditional indicators (C statistic, 0.802 [95% confidence interval (CI), 0.760-0.843] vs. 0.751 [95% CI, 0.706-0.796]; P = 5.56 × 10). Glucose, lactate, and citrate were among the fingerprints validated in the GDES cohort. Using these parsimonious and replicable fingerprints yielded similar improvements for predicting DR development (C statistic, 0.807 [95% CI, 0.711-0.903] vs. 0.617 [95% CI, 0.494-0.740]; P = 1.68 × 10) and progression (C statistic, 0.797 [95% CI, 0.712-0.882] vs. 0.665 [95% CI, 0.545-0.784]; P = 0.003) in the external GDES cohort. Improvements in NRIs, IDIs, and clinical usefulness also were evident in both cohorts (all P < 0.05). In addition, lactate and citrate were associated with microvascular damage across macular and optic nerve head regions among Chinese GDES (all P < 0.05). CONCLUSIONS: Metabolomic profiling may be effective in identifying robust fingerprints for predicting future DR development and progression, providing novel insights into the early and advanced stages of DR pathophysiology. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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