Ophthalmic Research最新文献

Introduction: Little research has examined the effects of anti-vascular endothelial growth factor therapy on subfoveal choroidal thickness (SCT), choroidal blood flow, aqueous flare, and humor levels of growth and inflammatory factors in patients with macular edema due to central retinal vein occlusion (CRVO).

Methods: In 58 patients with macular edema due to CRVO treated by intravitreal ranibizumab injection (IRI), we retrospectively assessed best-corrected visual acuity (BCVA, assessed as the logarithm of the minimum angle of resolution [logMAR]), 8 aqueous factors (by suspension array), mean blur rate (MBR; estimated by laser speckle flowgraphy as a measure of choroidal blood flow), aqueous flare (with a laser flare meter), and SCT and central macular thickness (CMT; by optical coherence tomography).

Results: After 4 weeks, IRI resulted in a significant improvement in BCVA and CMT and a significant reduction in SCT, choroidal MBR, and aqueous flare. SCT was significantly positively correlated with placental growth factor and significantly negatively correlated with platelet-derived growth factor-AA, and change in SCT was significantly negatively correlated with change in BCVA (logMAR). Aqueous flare was significantly negatively correlated with SCT.

Conclusion: Growth and inflammatory factors may be associated with SCT, and changes in SCT may be associated with changes in BCVA after IRI to treat macular edema due to CRVO.

Introduction: The aim of the study was to report 2-year outcomes of intravitreal injection of high-dose conbercept (1 mg 2 + PRN scheme) for subjects with myopic choroidal neovascularization (mCNV) and idiopathic choroidal neovascularization (iCNV) by optical coherence tomography angiography follow-up.

Methods: A total of 38 subjects (38 eyes) were enrolled in this retrospective study, which were divided into group A (mCNV, 20 subjects, 20 eyes) and group B (iCNV, 18 subjects, 18 eyes). All subjects received 1.0 mg of conbercept intravitreally at diagnosis and again 35 days later. Additional conbercept injection was administered upon findings of decreased best-corrected visual acuity (BCVA); metamorphosis aggravation, macular hemorrhage, or edema; increased central retinal thickness (CRT); or leakage observed by fluorescein angiography. The BCVA, CRT, and CNV areas of the two groups were evaluated at baseline and at 1, 2, 4, 6, 12, and 24 months after surgery.

Results: The BCVA of group A improved from 0.31 ± 0.16 logMAR at baseline to 0.12 ± 0.03 logMAR at the final follow-up (p < 0.001), while in group B the corresponding improvement was from 0.33 ± 0.16 logMAR at baseline to 0.12 ± 0.03 logMAR at the final follow-up (p < 0.001). Visual acuity improved in 17 subjects in group A and 15 in group B, while it remained stable in 3 subjects in each of groups A and B. CRT decreased from 311.83 ± 30.95 μm in group A and 351.17 ± 37.09 μm in group B preoperation to 229.56 ± 5.75 μm and 227.67 ± 4.98 μm at 24-month follow-up, respectively (p < 0.001 in groups A and B). Metamorphopsia was improved in subjects in groups A and B. CNV had disappeared in the two groups at the last postoperative visit. The BCVA, CRT, and CNV areas showed no statistical differences between the two groups at 6-, 12-, and 24-month follow-up (p > 0.05).

Conclusion: Intravitreal injection of conbercept (1 mg 2 + PRN scheme) is effective for treating patients with mCNV or iCNV, which can improve and stabilize vision as well as dramatically alleviate metamorphopsia.

Background: The performance of optical coherence tomography angiography (OCTA) in macular microvasculature of patients with amblyopia has been widely studied, but these studies have yielded different and controversial results.

Objectives: The aim of this study is to investigate retinal microvascular features in patients with amblyopia undergoing OCTA.

Methods: PubMed, Embase, and Web of Science were searched for published articles comparing the retinal microvascular features between individuals with amblyopia and controls until April 2022. The mean difference with a 95% confidence interval was used to assess continuous variables.

Results: The analysis included 17 studies. The whole vessel density of the superficial capillary plexus (SCPVD) was lower in amblyopic eyes (AE) than in normal eyes (NE) in 3 × 3 mm2 scans, while the perifoveal vessel density of superficial and deep capillary plexus was lower in 6 × 6 mm2 scans. The whole, parafoveal vessel density of deep capillary plexus (DCPVD) and parafoveal SCPVD were lower in both scans. The comparison between AE and fellow eyes (FE) revealed no statistical difference in all quadrants except the parafoveal and perifoveal SCPVD and the foveal DCPVD. Additionally, SCPVD in all quadrants except the fovea and DCPVD in all quadrants except the parafoveal were higher in FE compared to NE. No significant difference was found in the foveal avascular area between AE and NE, AE and FE, or NE and FE.

Conclusions: The retinal vessel density of superficial and deep capillary plexus in AE and FE was lower than in NE, and differences were more likely discovered using 6 × 6 mm2 scans. Consequently, OCTA might be explored as a diagnostic tool to identify and monitor patients with amblyopia.

Background: Intermittent exotropia is the most prevalent subtype of exotropia in children. Part-time occlusion (PTO) as an anti-suppression therapy was applied for nonsurgical management of intermittent exotropia.

Objective: The aim of the study was to compare the effectiveness of PTO therapy and observation in the treatment of intermittent exotropia.

Method: An exhaustive search of the literature from PubMed, Embase, Web of Science, and Cochrane Library databases was carried out until July 2022. No language restrictions were applied. The literature was rigorously screened against eligibility criteria. Weighted mean differences and 95% confidence interval (CI) were calculated.

Results: A total of 4 articles with 617 participants were included in this meta-analysis. Our pooled results showed that PTO exhibited superior effects compared to observation, with greater decrease in exotropia control at distance and near (MD = -0.38, 95% CI: -0.57 to -0.20, p < 0.001; MD = -0.36, 95% CI: -0.54 to -0.18, p < 0.001); patients subjected to PTO therapy had greater decrease in distance deviations (MD = -1.95, 95% CI: -3.13 to -0.76, p = 0.001), and there was greater improvement in near stereoacuity among the PTO group in comparison with the observation group (p < 0.001).

Conclusions: The present meta-analysis indicated that PTO therapy showed a better effect in improving control and near stereopsis and decreasing distance exodeviation angle of children with intermittent exotropia in comparison with observation.

Introduction: The colour vision in bestrophinopathies has not been assessed in detail so far. The aim of this study was to explore the extent to which distinct types of bestrophinopathies differ in regard to colour vision deficiencies using Farnsworth Dichotomous D-15 and Lanthony Desaturated D-15 panel tests.

Methods: Both D-15 tests were performed in 52 eyes of 26 patients with Best vitelliform macular dystrophy (BVMD) and 10 eyes of 5 patients with autosomal recessive bestrophinopathy (ARB). Two methods were used for a quantitative assessment of the colour vision deficiencies: moment of inertia method and Bowman method. The following parameters were calculated: confusion angle, confusion index (C-index), selectivity index (S-index), total error score (TES), and colour confusion index (CCI).

Results: The median value of confusion angle for all stages of BVMD fell into a narrow range around 62, indicating normal results. The median confusion angle value was 57 in ARB patients within a very wide range down to -82, indicating non-specific deficits. These differences were statistically significant. Significantly abnormal C-index and CCI values were found only in ARB patients, being 2.0 and 1.49, respectively. The majority of parameters of D-15 tests were independent of the visual acuity in both bestrophinopathies.

Conclusions: Elaborate evaluation of the D-15 panel tests might help establish a differential diagnosis between different bestrophinopathies, as the pattern of the colour vision loss is different between BVMD and ARB. The quantitative parameters of colour vision tests in bestrophinopathies are independent of the visual acuity.

Introduction: In proliferative diabetic retinopathy (PDR), retinal neovascularization is the essential pathogenic process that is linked to endothelial-to-mesenchymal transition (EndoMT) induced by high glucose (HG). This pathophysiological process may be regulated by a G-protein-coupled chemoattractant receptor FPR2 (mouse Fpr2), involved in inflammatory cell migration and proliferation. In the current study, we investigated the role of Fpr2 in regulating EndoMT and the underlying mechanisms during diabetic retinopathy progression.

Methods: FPR2 agonist or inhibitor was added to human microvascular endothelial cells (HMECs) exposed to normal glucose or HG. Morphologic, phenotypic, and functional changes of HMECs as well as the formation of microvasculature related to EndoMT were assessed. EndoMT biomarkers were detected in the retinal tissues of diabetic mice and fibrovascular epiretinal membranes (FVMs) from patients with PDR.

Results: HG upregulated FPR2 in HMECs, which triggered morphological changes, and the cells acquired mesenchymal phenotype, with enhanced cell migration, viability, and angiogenic process shown by tube formation and aortic ring sprouting. Inhibition of FPR2 attenuated HG-induced EndoMT and endothelial cell migration to form vessel-like tube structures. RNA sequence and protein analysis further revealed that inhibition of FPR2 decreased the expression of genes associated with EndoMT. ERK1/2 and P38 signaling pathway was activated in HMECs, promoting neovascularization in HG-induced EndoMT of HMECs. In vivo, increased expression of mesenchymal markers was detected in the retina of diabetic mice and FVMs from patients with PDR. FPR2 deficiency was associated with diminished EndoMT-related phenotypic changes in the retina of diabetic mice.

Conclusions: FPR2 is actively involved in the progression of EndoMT that may contribute to the pathogenesis of PDR. Thus, FPR2 may be a potential therapeutic target for PDR.

Introduction: The aim of this study was to evaluate the current management of RPE65 biallelic mutation-associated inherited retinal degeneration (RPE65-IRD) in Europe since market authorization of voretigene neparvovec (VN, LuxturnaTM) in 2018. By July 2022, over 200 patients have been treated outside the USA, of whom about 90% in Europe. We conducted among all centers of the European Vision Institute Clinical Research Network www.evicr.net and health care providers (HCPs) of the European Reference Network dedicated to Rare Eye Diseases (ERN-EYE) the second multinational survey on management of IRDs in Europe elaborated by www.evicr.net with a special focus on RPE65-IRD.

Methods: An electronic survey questionnaire with 48 questions specifically addressing RPE65-IRD (2019 survey 35) was developed and sent by June 2021 to 95 www.evicr.net centers and 40 ERN-EYE HCPs and affiliated members. Of note, 11 centers are members of both networks. Statistical analysis was performed with Excel and R.

Results: The overall response rate was 44% (55/124); 26 centers follow RPE65 biallelic mutation-associated IRD patients. By June 2021, 8/26 centers have treated 57 RPE65-IRD cases (1-19/center, median 6) and 43 planned for treatment (range 0-10/center, median 6). The overall age range was 3-52 years, and on average 22% of the patients did not (yet) qualify for treatment (range 2-60%/center, median 15%). Main reasons were too advanced (range 0-100, median 75%) or mild disease (range 0-100, median 0). Eighty-three percent of centers (10/12) that follow RPE65 mutation-associated IRD patients treated with VN participate in the PERCEIVE registry (EUPAS31153, www.encepp.eu. Quality of life and full-field stimulus test improvements had the highest scores of the survey-reported outcome parameters in VN treatment follow-up.

Conclusion: This second multinational survey on management of RPE65-IRD by www.evicr.net centers and ERN-EYE HCPs in Europe indicates that RPE65-IRD might be diagnosed more reliably in 2021 compared to 2019. By June 2021, 8/26 centers reported detailed results including VN treatment. Main reasons for non-treatment were too advanced or mild disease, followed by absence of 2 class 4 or 5 mutations on both alleles or because of a too young age. Patient satisfaction with treatment was estimated to be high by 50% of the centers.

Introduction: Numerous studies have demonstrated the use of artificial intelligence (AI) for early detection of referable diabetic retinopathy (RDR). A direct comparison of these multiple automated diabetic retinopathy (DR) image assessment softwares (ARIAs) is, however, challenging. We retrospectively compared the performance of two modern ARIAs, IDx-DR and Medios AI.

Methods: In this retrospective-comparative study, retinal images with sufficient image quality were run on both ARIAs. They were captured in 811 consecutive patients with diabetes visiting diabetic clinics in Poland. For each patient, four non-mydriatic images, 45° field of view, i.e., two sets of one optic disc and one macula-centered image using Topcon NW400 were captured. Images were manually graded for severity of DR as no DR, any DR (mild non-proliferative diabetic retinopathy [NPDR] or more severe disease), RDR (moderate NPDR or more severe disease and/or clinically significant diabetic macular edema [CSDME]), or sight-threatening DR (severe NPDR or more severe disease and/or CSDME) by certified graders. The ARIA output was compared to manual consensus image grading (reference standard).

Results: On 807 patients, based on consensus grading, there was no evidence of DR in 543 patients (67%). Any DR was seen in 264 (33%) patients, of which 174 (22%) were RDR and 41 (5%) were sight-threatening DR. The sensitivity of detecting RDR against reference standard grading was 95% (95% CI: 91, 98%) and the specificity was 80% (95% CI: 77, 83%) for Medios AI. They were 99% (95% CI: 96, 100%) and 68% (95% CI: 64, 72%) for IDx-DR, respectively.

Conclusion: Both the ARIAs achieved satisfactory accuracy, with few false negatives. Although false-positive results generate additional costs and workload, missed cases raise the most concern whenever automated screening is debated.

Introduction: The purpose of this study was to determine if conjunctival lymphangiogenesis can be induced using adenoviral delivery of vascular endothelial growth factor C (VEGF-C).

Methods: Seventeen New Zealand white rabbits received a subconjunctival injection containing 3.5 × 107 plaque-forming units of an adenoviral vector containing the gene-encoding VEGF-C (Ad-VEGF-C). The contralateral eye was used for control experiment (the same volume of either saline or an empty vector). After 2 weeks, the animals were examined with trypan blue conjunctival lymphangiography, and the eyes were harvested for histology and immunohistochemistry (podoplanin and CD31).

Results: Trypan blue conjunctival lymphangiography revealed significantly more extensive conjunctival vessel network in the Ad-VEGF-C group compared with control: 1.35 ± 0.67 versus 0.28 ± 0.17 vessel length/analysed area (p = <0.0001). This finding was confirmed with immunohistochemistry, where a significant increase in the number of lymphatic vessels was found compared to control; 34 ± 9 per mm2 versus 13 ± 8 per mm2 (p = 0.0019). Furthermore, there was a significant increase in lymphatic cross-sectional area; 32,500 ± 7,900 µm2 per mm2 versus 17,600 ± 9,700 µm2 per mm2 (p = 0.0149). Quantification of blood vessels revealed no significant difference in blood vessel density between Ad-VEGF-C and control; 19 ± 9 per mm2 versus 14 ± 8 per mm2 (p = 0.1971). There was no significant difference in total blood vessel area; 13,200 ± 7,600 µm2 per mm2 versus 7,100 ± 3,000 µm2 per mm2 (p = 0.0715). Eyes treated with an adenoviral vector (VEGF-C or empty vector) responded with a reactive cellular response, predominantly lymphocytes, towards the vector.

Conclusion: The study demonstrates the feasibility of inducing conjunctival lymphangiogenesis with a single subconjunctival injection of Ad-VEGF-C. Future studies will explore how this can be used with a therapeutic purpose.

Introduction: The aim of this study was to describe and evaluate double PreserFlo MicroShunt implantation as a modified micro-invasive glaucoma surgery technique and to retrospectively compare the outcomes in a cohort of glaucoma patients with single or double implantation.

Materials and methods: A retrospective data analysis of 57 glaucoma patients who consecutively underwent PreserFlo implantation was performed. Medical records were examined for patients' demographics, glaucoma type, intraocular pressure (IOP), medication, complications, and re-interventions. Two groups with single (n = 29) or double (n = 28) implantation were formed, and the outcomes were compared. In cases of two-stage double implantation (n = 17), the courses of the initial and the second implantations were compared.

Results: Mean preoperative IOP was significantly higher in the double compared to the single implantation group (29.4 ± 10.0 mm Hg; 21.7 ± 8.2 mm Hg; p = 0.003). Postoperatively, IOP was significantly lower in the double implantation group at various time-points (day 1, week 1, months 3 and 6; all p < 0.021). In the subgroup with two-stage procedures, mean preoperative IOP was 24.5 ± 8.5 mm Hg and 29.8 ± 10.1 mm Hg, respectively (p = 0.128). While immediately postoperatively, mean IOP lowering was clinically significant and similar following both procedures, the longer sustainable effect was observed after the second procedure (month 12: 25.5 ± 7.5 mm Hg; 12.4 ± 4.8 mm Hg; p = 0.001). No serious complications were observed.

Discussion/conclusion: Double PreserFlo implantation appears safe and efficient for lowering IOP in glaucoma patients. Our preliminary findings suggest that double is superior to single implantation in terms of IOP lowering and the need for additional topical medication. Patients with insufficient IOP lowering following single implantation may benefit from a second implantation. Further research is warranted to evaluate double implantation as a first-line, one-stage procedure.