Investigative ophthalmology & visual science最新文献

Purpose: Outer retinal band integrity strongly predicts late age-related macular degeneration (AMD). However, it is often assessed subjectively as "continuity" using inconsistent definitions. Alternatively, "curvature" of the outer retinal bands is a quantitative metric that strongly correlates with AMD biomarkers and can screen for intermediate AMD. We evaluated the prognostic ability of retinal pigment epithelium (RPE) and ellipsoid zone (EZ) curvature for late AMD against outer retinal band continuity, pigmentary abnormalities, reticular pseudodrusen, and drusen volume.

Methods: Consecutive patients with intermediate AMD who progressed to late AMD (n = 17) or remained stable (n = 42) were recruited. RPE and EZ curvature were quantified as a ratio of their lengths over Bruch's membrane using the sinuosity method of assessing river curvature, where a ratio of ∼1 indicates no outer retinal pathology. RPE, EZ, and Bruch's membrane were manually segmented and their lengths automatically extracted. The primary outcomes were outer retinal sinuosity and the odds ratio of predicting late AMD.

Results: Mean follow-up time for progressors and nonprogressors was 4.4 and 3.6 years. RPE sinuosity was strongly associated with pigmentary abnormalities (P = 0.001) and drusen volume (P = 0.004) but not reticular pseudodrusen (P = 0.28). RPE sinuosity >1.03 was the strongest predictor of late AMD developing within 5 years (15 [2.9-75]) and across the study period (25 [2.3-282]). Drusen volume >0.03 mm3 was the strongest predictor of progression within 2 years (33 [2.5-426]), and RPD could not independently predict progression within any time frame.

Conclusions: RPE curvature is a promising, quantitative outer retinal biomarker that can prognosticate late AMD and potentially enhance prognostic models.

Purpose: To evaluate the correlation between the macular ganglion cell complex (GCC) thickness measured with manually corrected segmentation and visual function in individuals with chronic Leber hereditary optic neuropathy (LHON).

Methods: Twenty-six chronic LHON subjects (60% treated with idebenone or Q10) from the Swedish LHON registry were enrolled. Best-corrected visual acuity (BCVA), visual field tests, and optical coherence tomography (OCT) were performed. Visual field was evaluated with the Haag-Streit Octopus 900 with the Esterman test and a custom 30° test. Canon OCT-HS100 scans were exported to the Iowa Reference Algorithm. GCC thickness was obtained after the segmentation was corrected manually in nine macular sectors.

Results: The GCC thickness was overestimated by 16 to 30 µm in different macular sectors with the automated segmentation compared with the corrected (P < 0.001). GCC thickness in all sectors showed significant correlation with all functional parameters. The strongest correlation was seen for the external temporal sector (BCVA: r = 0.604, P < 0.001; mean defect: r = 0.457, P = 0.001; Esterman score: r = 0.421, P = 0.003). No differences were seen between treated and untreated subjects with regard to GCC and visual field scores (P > 0.05), but BCVA was better among treated subjects (P = 0.017).

Conclusions: The corrected GCC thickness showed correlation with visual function in chronic LHON subjects. The frequently occurring segmentation errors in OCT measurements related to chronic LHON can potentially be misleading in monitoring of disease progression and in evaluating the treatment effects. Precise measurements of GCC could serve as a sensitive tool to monitor structural changes in LHON. We therefore emphasize the importance of careful evaluation of the accuracy of OCT segmentation.

Purpose: The purpose of this study was to assess the natural history of the foveal cone mosaic in CNGA3-associated achromatopsia (ACHM).

Methods: Thirteen eyes from 10 genetically confirmed patients underwent longitudinal imaging with optical coherence tomography (OCT) and non-confocal split detection adaptive optics scanning light ophthalmoscopy (AOSLO). OCT scans assessed outer nuclear layer (ONL) thickness, foveal ellipsoid zone (EZ) disruption, and foveal hypoplasia. AOSLO images were analyzed to calculate peak foveal cone density (PCD) and mean inter-cell distance (ICD) between cones. Mixed effects models were used to analyze the rate of annual change of PCD and ICD.

Results: Mean (±SD) age at visits was 29 ± 10 years, with a follow-up of 2.6 ± 1 years. There was no change in ONL thickness, degree of EZ disruption, or foveal hypoplasia over the follow-up period. We also observed a stable foveal cone mosaic using AOSLO imaging, with no significant change in PCD or ICD. Mean PCD was 15,346 cones/mm² at the mean age of 29 years old (cf. 64,000-324,000 cones/mm² in previously reported healthy controls), with a mean rate of change of -117.79 cones/mm² (0.8%) per year, P = 0.130. Mean ICD at the mean age was 13.82 µm, with a rate of change of 0.17 µm per year, P = 0.83.

Conclusions: CNGA3-associated ACHM displays stable foveal cone structure over time with a similar rate of change to CNGB3-associated ACHM (2% decline per year). The stable PCD, small cohort, and large variability within the cohort means significant age associations were not detected.

Purpose: The purpose of this study was to investigate whether the rapid rate of peripapillary retinal nerve fiber layer (pRNFL) thinning in short-term is associated with the future risk of developing diabetic retinopathy (DR).

Methods: This prospective cohort study utilized 4-year follow-up data from the Guangzhou Diabetic Eye Study. The pRNFL thickness was measured by optical coherence tomography (OCT). DR was graded by seven-field fundus photography after dilation of the pupil. Correlations between pRNFL thinning rate and DR were analyzed using logistic regression. The additive predictive value of the prediction model was assessed using the C-index, net reclassification index (NRI), and integrated discriminant improvement index (IDI).

Results: A total of 1012 patients with diabetes (1012 eyes) without DR at both baseline and 1-year follow-up were included in this study. Over the 4-year follow-up, 132 eyes (13%) developed DR. After adjusting for confounding factors, a faster rate of initial pRNFL thinning was significantly associated with the risk of DR (odds ratio per standard deviation [SD] decrease = 1.15, 95% confidence interval [CI] = 1.08 to 1.23, P < 0.001). Incorporating either the baseline pRNFL thickness or its thinning rate into conventional prediction models significantly improved the discriminatory power. Adding the rate of pRNFL thinning further enhanced the discriminative power compared with models with only baseline pRNFL thickness (C-index increased from 0.685 to 0.731, P = 0.040). The IDI and NRI were 0.114 and 0.463, respectively (P < 0.001).

Conclusions: The rate of initial pRNFL thinning was associated with DR occurrence and improved discriminatory power of traditional predictive models. This provides new insights into the management and screening of DR.

Purpose: The diagnosis and management of dry eye disease (DED) could be complicated by the discordance between DED-related symptoms and signs. We performed a cross-sectional study to investigate the factors of and develop predictive models for the discrepancy in DED symptomatology.

Methods: We used data from 3455 participants, 21 to 89 years old, from the Sjögren's International Collaborative Clinical Alliance study. We performed a multivariable stepwise linear regression model with backward elimination and Bayesian information criteria to select predictors for the discordance in DES symptomatology, which was defined as the difference between the rank score of Ocular Surface Disease Index 6 (OSDI-6) and the rank score of ocular staining score (OSS).

Results: Ten predictors, such as "vitality," "immunomodulating drugs," sensory symptoms," and "ethnicity," remained in the final models, achieving an adjusted R2 (aR2) of 0.35 (95% confidence interval [CI], 0.32-0.39). Specifically, medication use explained 19% (95% CI, 0.17-0.22) of the variance in the outcome, followed by medical history (aR2 = 0.18; 95% CI, 0.15-0.21). Health-related quality of life contributed 16% to the variance in the outcome (95% CI, 0.13-0.19), and, last, demographics contributed 11% (95% CI, 0.09-0.13).

Conclusions: Our results suggest that individuals of Asian descent and those using immunomodulating medications often present with severe ocular signs that necessitate regular ophthalmological evaluations, even in the absence of proportionate ocular symptoms. Additionally, ocular symptoms, when accompanied by abnormal sensations in other parts of the body, could indicate systemic conditions that require further investigation and medical care.

Purpose: Our previous study indicated that exosomes derived from mouse adipose-derived mesenchymal stem cells (mADSC-Exos) alleviated the benzalkonium chloride (BAC)-induced mouse dry eye model. However, the specific active molecules in mADSC-Exos that contribute to anti-dry eye therapy remain unidentified. In this study, we aimed to investigate the efficacy and mechanisms of miR-223-3p derived from mADSC-Exos in dry eye models.

Methods: Enzyme-linked immunosorbent assay (ELISA) experiments were conducted to determine miR-223-3p derived from mADSC-Exos that exerted anti-inflammatory effects on hyperosmolarity-induced mouse corneal epithelial cells (MCECs). The therapeutic efficacy of miR-223-3p was evaluated in mice with dry eye induced by either BAC or scopolamine (Scop). Mice were randomly assigned to 5 groups: sham, model, miR-223-3p overexpression, miR-223-3p knockdown, and 0.1% pranoprofen (positive group). Post-treatment, the severity of dry eye symptoms, and the pro-inflammatory cytokine levels were assessed. The effect of miR-223-3p on silencing the target gene was verified using ELISA and dual luciferase reporter assays.

Results: The mADSC-Exos that knocked out miR-223-3p did not reduce interleukin (IL)-6 content. Supplementing with miR-223-3p could restore the reduction of IL-6. The miR-223-3p effectively ameliorated ocular surface damage and decreased pro-inflammatory cytokines or chemokines in both BAC- and Scop-induced mouse dry eye models. Furthermore, miR-223-3p inhibited cell apoptosis. F-box and WD repeat domain-containing 7 (Fbxw7) was the potential direct target of miR-223-3p. The miR-223-3p suppressed the 3'-untranslated region of Fbxw7. The Fbxw7 knockdown suppressed hyperosmolarity-induced inflammation in MCECs.

Conclusions: The mADSC-derived exosomal miR-223-3p mitigates ocular surface damage and inflammation, indicating its potential as a promising treatment option for dry eye.

Purpose: To investigate if changes in vessel density (VD) and the foveal avascular zone (FAZ) occur in the preclinical phase of Alzheimer's disease (pAD) over time.

Methods: Optical coherence tomography angiography (OCTA) was used to image VD and FAZ at baseline and for a follow-up period of 2 years. Positron emission tomography (PET) was used to determine the amyloid beta (Aβ) status of participants.

Results: The VD and FAZ of 148 participants (54% female) were analyzed at baseline and follow-up (mean time between measurements, 2.24 ± 0.35 years). The mean age of the participants was 68.3 ± 6.0 years at baseline and 70.3 ± 5.9 years at follow-up. Participants were divided into three groups: control group, participants who had negative Aβ status at both measurements (Aβ-, n = 116); converter group, participants who transitioned from negative to positive between baseline and follow-up (Aβ-+, n = 18); and participants who were consistently positive at both visits (Aβ++, n = 14). The VD of both Aβ+ groups demonstrated non-significant increases over time in both macula and optic nerve head (ONH) regions. The Aβ- group was found to be significantly higher in both ONH and macular regions. The VD of the Aβ++ group was significantly higher in the macula inner and outer rings compared to the Aβ-+ and Aβ- groups. No significant change was found in FAZ values over time.

Conclusions: Alterations in VD seem to manifest already in pAD, exhibiting distinct variations between the ONH and macula. Further longitudinal studies with a longer follow-up design and known amyloid pathology should be undertaken to validate these observations.