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Research update: Issue 499

31 May 2021


Anti-VEGF-resistant subretinal fluid is associated with better vision and reduced risk of macular atrophy

Br J Ophthalmol. 2021 May 26;bjophthalmol-2020-318688.

Marco A Zarbin, Lauren Hill, Andreas Maunz, Martin Gliem, Ivaylo Stoilov 

PMID: 34039560 DOI: 10.1136/bjophthalmol-2020-318688

Background/aim: To evaluate relationships between subretinal fluid (SRF), macular atrophy (MA) and visual outcomes in ranibizumab-treated neovascular age-related macular degeneration (nAMD).

Methods: This post hoc HARBOR trial (NCT00891735) analysis included ranibizumab-treated (0.5 or 2.0 mg, monthly or as-needed, all treatment arms pooled) eyes with nAMD and baseline (screening, baseline and week 1) SRF. SRF presence, SRF thickness (0, >0-50, >50-100 and >100 µm) and subretinal fluid volume (SRFV) were determined by spectral domain optical coherence tomography (SD-OCT). Best-corrected visual acuity (BCVA) was assessed. MA was identified using fluorescein angiograms and colour fundus photographs, as well as SD-OCT.

Results: Seven hundred eighty-five of 1097 eyes met analysis criteria. In eyes without baseline MA, residual versus no SRF at month (M) 3 was associated with lower MA rates at M12 (5.1% vs 22.1%) and M24 (13.3% vs 31.2%) (both p<0.0001); MA percentages at M12/M24 were similar among patients with residual SRF at M6. Higher baseline SRFV was associated with a lower MA rate. Greater mean BCVA was observed with residual SRF of any thickness (>0-50 µm, 71.2 letters; >50-100 µm, 71.3 letters; >100 µm, 69.2 letters) versus no SRF (63.6 letters), but the change in BCVA from baseline to M12 or M24 was the same for eyes with or without treatment-resistant subretinal fluid (TR-SRF) at M3 or M6.

Conclusion: TR-SRF was not detrimental to vision outcomes over 2 years, regardless of thickness. MA rates were significantly higher without TR-SRF.

The prognostic role of optical coherence tomography in diabetic macular edema patients undergoing early dexamethasone implant shift

Eur J Ophthalmol. 2021 May 21;11206721211019569.

Mehmet Murat Uzel, Eyyup Karahan, Melek Koroglu Canli, Cenap Guler 

PMID: 34020568 DOI: 10.1177/11206721211019569

Purpose: To determine the prognostic characteristics of optical coherence tomography (OCT) parameters by evaluating diabetic macular edema (DME) patients with early dexamethasone (DEX) shift after three doses of intravitreal ranibizumab (RNB) injection.

Methods: Fifty-four eyes of 34 patients who had DEX implant after three doses of RNB were included in this retrospective study. Early DEX shift includes patients who received direct DEX implant replacement after three doses of RNB load. Baseline OCT values and factors affecting best corrected visual acuity (BCVA) and central macular thickness (CMT) response were analyzed with logistic regression analyses.

Results: The presence of subretinal fluid and hyperreflective spot (HRS) >20 were found to be a negative predictive factor for anatomical response. (p = 0.009, p = 0.001, respectively) Low initial BCVA creates a positive effect on visual gain.( p = 0.041) Giant outer nuclear layer cysts, completely disrupted inner segment-outer segment and HRS > 20 have a negative effect on visual gain. (p = 0.025, p = 0.043, p = 0.023, respectively) According to the receiver operating characteristic analysis, the subretinal fluid volume threshold at which >20% reduction in CMT occurs was determined to be 0.85 mm3. (sensitivity 70%, specificity 84% area under the curve 0.817, p = 0.021).

Conclusion: The presence of high number of HRS and high subretinal fluid volume at the baseline negatively affect prognosis even in patient groups with early DEX shift.


Home vision monitoring in patients with maculopathy: Real-life study of the OdySight application

J Fr Ophtalmol. 2021 May 20;S0181-5512(21)00242-4.

S Guigou, T Michel, P-Y Mérité, L Coupier, F Meyer  

PMID: 34024655 DOI: 10.1016/j.jfo.2020.09.034

Introduction: The goal of the present study was to analyze the implementation and clinical efficacy of OdySight, a mobile medical application for the remote monitoring of patients with maculopathy.

Materials and methods: In all, 60 patients with edematous maculopathies receiving traditional clinical treatment (PRN or Treat & Extend) were provided with OdySight to detect changes in visual acuity from home. To determine both the feasibility and reliability of the application, its use by patients (both testing and game play), as well as the processing of alerts by the clinical team, were analyzed during the first year.

Results: The female-to-male ratio was 3:2, with a mean age of 64 years. 52% of patients presented with age-related macular degeneration, 31% with high myopia, 11% with retinal vein occlusion, and 6% with diabetic maculopathy. The conversion rate (defined as the percentage of patients completing at least one test following prescription) and the nine-month retention rate (percentage of active patients) were 61% and 24% respectively. Patients aged 50 to 70 years and those whose use of the app included game play represent 75% of active patients at 9 months. The 22 active patients performed 483 visual acuity tests, completed 1,667 game sessions, and underwent 77 in-person consultations. During the trial period, the clinical team processed 19 alerts, on average in fewer than 6 days. Decreases in visual acuity were detected with a sensitivity of 92% and specificity of 99%.

Discussion: The use of connected and mobile devices today is widespread, as is interest in mobile medical applications. Long-term treatments for maculopathies can be a difficult burden to bear, both for patients and healthcare practitioners. Overcoming the challenges associated with the successful remote detection of recurrences thus represents a significant opportunity for improving patient care. The implementation of novel digital tools requires the cooperation of the clinical team as a whole, to both inform and motivate patients. OdySight demonstrates satisfactory detection rates, thanks to reliable and reproducible home testing, and can thus serve as a supplementary tool for patients whose consultations are often spaced several months apart. Implementation can be nonetheless improved by facilitating alert processing, a goal which necessitates active adaptation of clinical practices. In general, active patients were very satisfied with this personalized service.

Conclusion: Improved medical support, plus the amusing nature of the tests and games, both bolster long-term use of the OdySight app. The application allows for the remote monitoring of changes in visual acuity and affords patients and practitioners an added level of protection, particularly during long intervals between treatments and at the end of a treatment course. To ensure proper implementation, clinics should focus on reinforcing and modernizing the clinical pathway, from patient intake to the injection room.

Characterizing Progression to Neovascular AMD in Fellow Eyes of Patients Treated With Intravitreal Anti-VEGF Injections

Ophthalmic Surg Lasers Imaging Retina. 2021 Mar;52(3):123-128.

Matthew R Starr, David Xu, Nicholas Boucher, Namrata Saroj, Luv G Patel, Michael Ammar, Ravi R Pandit, Thomas L Jenkins, Allen C Ho

PMID: 34038686 DOI: 10.3928/23258160-20210302-02

Background and objective: The purpose of this study was to assess the real-world incidence of conversion to bilateral neovascular age-related macular degeneration (nAMD) following treatment initiation of nAMD in the initial eye.

Patients and methods: This was a retrospective cohort of electronic health records from retinal centers across the United States (Vestrum Database) of all patients with unilateral nAMD treated with anti-vascular endothelial growth factor therapy.

Results: A total of 22,553 patients with unilateral nAMD were included. Fellow eyes of 8,522 patients (38%) converted to nAMD. Among these, 2,639 (12%), 2,030 (9%), and 1,802 (8%) patients converted in Years 1, 2, and 3, respectively, after diagnosis in the first eye. Fellow eyes had better vision at conversion and 1 year following conversion.

Conclusions: The fellow eye should be monitored at regular intervals to detect signs of neovascularization. Fellow eyes presented with significantly better vision at diagnosis than the initial eye and maintained better visual acuity with less injections. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:123-128.].

Differentiating Exudative Macular Degeneration and Polypoidal Choroidal Vasculopathy Using Optical Coherence Tomography B-scan

Ophthalmol Retina. 2021 May 19;S2468-6530(21)00168-8.

Gregg T Kokame, Jase N Omizo, Kelli A Kokame, Maya L Yamane  

PMID: 34022443 DOI: 10.1016/j.oret.2021.05.009

Purpose: Although polypoidal choroidal vasculopathy (PCV) is best diagnosed with indocyanine green angiography (ICGA), ICGA is often unavailable or not ordered. Optical coherence tomography (OCT) is widely available, and OCT B-scan can visualize polypoidal lesions diagnostic of PCV as inverted U-shaped elevations of the retinal pigment epithelium (RPE) with heterogeneous reflectivity and sometimes ring-shaped lesions within the polypoidal lesion. This study aims to differentiate findings between eyes diagnosed with PCV or typical exudative age-related macular degeneration (AMD) using ICGA, then comparing findings noted on the OCT B-scan line scan in each group.

Design: Retrospective, chart review.

Methods: Clinical features of eyes with PCV and typical exudative AMD were compared based on ICGA. Eyes with PCV were evaluated for inverted U-shaped polypoidal lesions which are the main differentiating finding of PCV from typical exudative AMD. Data collected included: presence of subretinal fluid (SRF), macular edema or intraretinal edema (ME), subretinal hyperreflective material (SHRM), and retinal pigment epithelial detachment (RPED). These findings were evaluated in two parts: baseline and after six to nine months of antiangiogenic therapy. Additionally, analysis was performed for the presence of polypoidal lesions before and after treatment.

Results: 112 eyes of 106 patients were included. 69 eyes were diagnosed with PCV and 43 with typical exudative AMD. Compared to AMD eyes, PCV eyes had an increased prevalence of SRF at baseline and after six to nine months of treatment, but the prevalence of ME, SHRM, and RPED were similar at baseline and at six to nine months after treatment. In PCV eyes, the presence of visible polypoidal lesions decreased from 56.5% to 24.6% after treatment.

Conclusion: If PCV is suspected in an anti-vascular endothelial growth factor (anti-VEGF) resistant case of exudative AMD, in the absence of ICGA availability, it’s important to look at the baseline B-scan OCT prior to therapy for evidence of polypoidal lesions. The characteristic inverted U-shaped elevation was present in over half of PCV eyes on OCT B-scan at baseline but disappeared following antiangiogenic therapy in 56.4% of cases where this was initially identified. SRF was more prevalent in PCV eyes than non-PCV AMD eyes.

Attention Based Deep Learning System for Automated Diagnoses of Age-Related Macular Degeneration in Optical Coherence Tomography Images

Med Phys. 2021 May 27.

Yan Yan, Kai Jin, Zhiyuan Gao, Xiaoling Huang, Fanyi Wang, Yao Wang, Juan Ye 

PMID: 34042194 DOI: 10.1002/mp.15002

Purpose: The progression of age-related macular degeneration (AMD) is critical to treatment decisions in clinical practice. The disease can be classified into four categories namely, drusen, inactive choroidal neovascularization (CNV), active CNV, and normal, according to severity based on optical coherence tomography (OCT) images. Interpreting numerous OCT images is still time-consuming and labor-intensive, especially for the detection of the CNV activity. To address this problem, we developed a deep learning (DL) system based on OCT images, with the assistance of an attention mechanism, to automatically diagnose AMD.

Methods: A public dataset (total 51,140 OCT images) and a private dataset (total 4,951 OCT images) were utilized as a training dataset and a clinical validation dataset, respectively, to develop the DL model. A ResNet-34 DL model, with convolutional block attention module (CBAM) block integrated into each unit, was pre-trained on the public dataset first and then finetuned on our private dataset to automatically diagnose AMD and assist clinical decision-making. GradCam, a visualization technique, was used to improve the interpretability of our model.

Results: The precision and recall of our model were, respectively, 84.3% and 87.3% for drusen, 81.2% and 80.0% for inactive CNV, 97.7% and 90.2% for active CNV, and 93.7% and 96.5% for normal. The area under the curve (AUC) corresponding to drusen, inactive CNV, active CNV, and normal for our model reached 0.9395, 0.9476, 0.9880, and 0.9925 respectively. The heatmaps indicated a high level of correspondence in the region of interest between our model and ophthalmologists on the diagnosis.

Conclusions: The implementation of finetuning and attention mechanism improve the performance of our model in a distinct dataset. Our model successfully assisted in the diagnosis of AMD and achieved a detection precision and recall equal to those of ophthalmologists. The results of our study could contribute to the precise diagnosis of and decision-making regarding AMD.

Association Between the Degree of Inclusion of Components Identified on Fluorescein or Indocyanine Green Angiography in Target Spots and Relapse of Exudate in Eyes with Polypoidal Choroidal Vasculopathy and Typical Age-Related Macular Degeneration After Photodynamic Therapy

Clin Ophthalmol. 2021 May 18;15:2063-2075.

Izumi Yoshida, Hikari Taniguchi, Masashi Sakamoto, Takatoshi Maeno 

PMID: 34040342 PMCID: PMC8140940 DOI: 10.2147/OPTH.S305238

Purpose: To investigate the association between the inclusion of components identified on images in target spots of photodynamic therapy (PDT) and exudate relapse in eyes with age-related macular degeneration (AMD).

Methods: Forty-one eyes (39 patients) with polypoidal choroidal vasculopathy (PCV) and 32 eyes (31 patients) with typical AMD (tAMD) who underwent PDT were retrospectively investigated. Each component identified on fluorescein (FA) or indocyanine angiography (IA), optical coherence tomography (OCT), or color photography was graded as not depicted, covered with a margin ≥500 µm or <500 µm, and protruding. Associations between these grades and the dry rate (proportion of subjects with continuous absence of exudate over following 12-month period) and the relapse index (2 × number of injections administered + accumulation of exudate for 12 months post-PDT) were investigated.

Results: In PCV, the association between worse coverage and decreasing dry rates for feeder vessels and polyps approached statistical significance. With coverage margins ≥500 µm, dry rate tended to be greater than with coverage margins <500 µm for feeder vessels, classic lesions, and occult lesions on FA. In the tAMD group, coverage with margins ≥500 µm tended to yield a higher dry rate than coverage with margins <500 µm for CNV on IA. Coverage with margins ≥500 µm for occult and classic lesions on FA yielded no dry subjects, and all subjects with classic lesions or staining had recurrence (P = 0.009 and 0.050). Worse coverage and worse dry rate in PCV and worse relapse index in tAMD were related to pigment epithelial detachment on OCT (P = 0.040 and 0.006).

Conclusion: Polyps in PCV and pigment epithelial detachment (PED) in tAMD were verified as appropriate targets, corresponding to the existing guidelines, and feeder vessels, classic lesion, occult lesion, and PED in PCV and CNV on IA in tAMD were suggested as further targets. OCT was superior to FA for evaluating PED.

Directional Reflectivity of the Ellipsoid Zone in Dry Age-Related Macular Degeneration

Ophthalmic Surg Lasers Imaging Retina. 2021 Mar;52(3):145-152.

Shane M Griffin, Yali Jia, Alicia J Johnson, Bhavna J Antony, H Richard McDonald, Robert N Johnson, Brandon J Lujan

PMID: 34038689 DOI: 10.3928/23258160-20210302-05

Background and objective: Ellipsoid zone (EZ) reflectivity on optical coherence tomography (OCT) is affected by the orientation of the scanning beam. The authors sought to determine how directional reflectivity changes in dry age-related macular degeneration (AMD).

Patients and methods: Retrospective image analysis included 17 control and 20 dry AMD subjects. Directional OCT (D-OCT) was performed using multiple displaced pupil entrance positions. EZ pixel values and apparent incidence angles were measured.

Results: EZ reflectivity decreased in off-axis scans in controls (P < .001), AMD areas between drusen (P < .001), and AMD areas overlying drusen (P < .001). The magnitude of decrement in EZ reflectivity was significantly higher when incidence angles exceeded 10° in controls than in AMD areas between drusen (P = .024).

Conclusion: EZ reflectivity in dry AMD may vary by incident angle of light less than in controls, possibly indicating alteration of photoreceptor orientation or integrity. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:145-152.].

Assessing the Clinical Utility of Expanded Macular OCTs Using Machine Learning

Transl Vis Sci Technol. 2021 May 3;10(6):32.

Andrew C Lin, Cecilia S Lee, Marian Blazes, Aaron Y Lee, Michael B Gorin  

PMID: 34038502 DOI: 10.1167/tvst.10.6.32

Purpose: Optical coherence tomography (OCT) is widely used in the management of retinal pathologies, including age-related macular degeneration (AMD), diabetic macular edema (DME), and primary open-angle glaucoma (POAG). We used machine learning techniques to understand diagnostic performance gains from expanding macular OCT B-scans compared with foveal-only OCT B-scans for these conditions.

Methods: Electronic medical records were extracted to obtain 61 B-scans per eye from patients with AMD, diabetic retinopathy, or POAG. We constructed deep neural networks and random forest ensembles and generated area under the receiver operating characteristic (AUROC) and area under the precision recall (AUPR) curves.

Results: After extracting 630,000 OCT images, we achieved improved AUROC and AUPR curves when comparing the central image (one B-scan) to all images (61 B-scans). The AUROC and AUPR points of diminishing return for diagnostic accuracy for macular OCT coverage were found to be within 2.75 to 4.00 mm (14-19 B-scans), 4.25 to 4.50 mm (20-21 B-scans), and 4.50 to 6.25 mm (21-28 B-scans) for AMD, DME, and POAG, respectively. All models with >0.25 mm of coverage had statistically significantly improved AUROC/AUPR curves for all diseases (P < 0.05).

Conclusions: Systematically expanded macular coverage models demonstrated significant differences in total macular coverage required for improved diagnostic accuracy, with the largest macular area being relevant in POAG followed by DME and then AMD. These findings support our hypothesis that the extent of macular coverage by OCT imaging in the clinical setting, for any of the three major disorders, has a measurable impact on the functionality of artificial intelligence decision support.

Translational relevance: We used machine learning techniques to improve OCT imaging standards for common retinal disease diagnoses.


Geniposide alleviates choroidal neovascularization by downregulating HB-EGF release from RPE cells by downregulating the miR-145-5p/NF-κB axis

Exp Eye Res. 2021 May 19;208:108624.

Jiayi Gu, Zhaoxian Qiu, Lele Li, Bai Qin, Yamei Zhou, Yu Liu, Xiaojuan Liu, Manhui Zhu, Aimin Sang

PMID: 34022175 DOI: 10.1016/j.exer.2021.108624

Age-related macular degeneration (AMD), mainly wet AMD, is the major reason for nonreversible vision loss worldwide. Choroidal neovascularization (CNV) is a characteristic pathological manifestation of wet AMD. Stress or injury to the retinal pigment epithelium (RPE) induces proangiogenic factors that drive CNV. An iridoid glycoside extracted from the fruit of gardenia, geniposide (GEN) plays an antiangiogenic role. In this study, GEN inhibited the transcription and expression of heparin-binding epidermal growth factor (HB-EGF), a proangiogenic factor, in hypoxic RPE cells and a mouse laser-induced CNV model. Inhibition of glucagon-like peptide-1 receptor (GLP-1R), a GEN receptor blocker, eliminated the protective effect of GEN. Additionally, GEN decreased the transcription and expression of HB-EGF in hypoxia-exposed RPE cells by downregulating the miR-145-5p/NF-κB axis. Therefore, our research provides a promising novel strategy for wet AMD therapy.

Effect of a TSPO ligand on retinal pigment epithelial cholesterol homeostasis in high-fat fed mice, implication for age-related macular degeneration

Exp Eye Res. 2021 May 20;208:108625.

Lincoln Biswas, Khalid Subhi Ibrahim, Xing Li, Xinzhi Zhou, Zhihong Zeng, John Craft, Xinhua Shu

PMID: 34022174 DOI: 10.1016/j.exer.2021.108625

Age-related Macular Degeneration (AMD) is a major cause of sight impairment in the elderly with complex aetiology involving genetics and environment and with limited therapeutic options which have limited efficacy. We have previously shown in a mouse-model of the condition, induced by feeding a high fat diet, that adverse effects of the diet can be reversed by co-administration of the TSPO activator, etifoxine. We extend those observations showing improvements in retinal pigment epithelial (RPE) cells with decreased lipids and enhanced expression of cholesterol metabolism and transport enzymes. Further, etifoxine decreased levels of reactive oxygen species (ROS) in RPE and inflammatory cytokines in RPE and serum. With respect to gut microbiome, we found that organisms abundant in the high fat condition (e.g. in the genus Anaerotruncus and Oscillospira) and implicated in AMD, were much less abundant after etifoxine treatment. The changes in gut flora were associated with the predicted production of metabolites of benefit to the retina including tryptophan and other amino acids and taurine, an essential component of the retina necessary to counteract ROS. These novel observations strengthen earlier conclusions that the mechanisms behind improvements in etifoxine-induced retinal physiology involve an interaction between effects on the host and the gut microbiome.


Anti-VEGF Treatment Patterns in Patients With Wet Age-Related Macular Degeneration in Clinical Practice

Ophthalmic Surg Lasers Imaging Retina. 2021 May;52(5):263-272.

Rishi P Singh, Justin S Yu, Guruprasad B, Neetu Agashivala

PMID: 34044715 DOI: 10.3928/23258160-20210429-04

Background and objective: To characterize on-label anti-vascular endothelial growth factor (VEGF) treatment patterns in patients with wet age-related macular degeneration (AMD) in clinical practice in the U.S.

Patients and methods: Retrospective cohort analysis using administrative claims data from the IQVIA Open Source Databases. Treatment-naïve patients in the U.S. who received one or more wet AMD-related anti-VEGF injection from July 1, 2013, to April 30, 2017, were included. The main outcome was the injection interval closest to Month 12.

Results: This study included 21,960 patients who initiated an anti-VEGF agent (ranibizumab, aflibercept, or bevacizumab): 5,489 initiated aflibercept and 4,253 initiated ranibizumab. Among ranibizumab, aflibercept, and all anti-VEGF eyes, 38.1% (n = 2,035), 33.5% (n = 3,262), and 40.0% (n = 12,505) of patient eyes had injection intervals of less than 8 weeks, respectively, at Month 12 with the mean (standard deviation) number of injections over 12 months being 8.0 (2.4), 7.6 (2.4), and 7.8 (2.5).

Conclusion: A substantial proportion of patients receive injections more frequently than every 8 weeks within the first year of treatment. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:263-272.].

Real-World Treatment Patterns in a Population With Neovascular AMD Treated With Anti-VEGF Agents

Ophthalmic Surg Lasers Imaging Retina. 2021 Apr;52(4):190-198.

Catherine A Urbano, Christopher Maatouk, Tyler Greenlee, Andrew Chen, Thais F Conti, Isaac Briskin, Rishi P Singh

PMID: 34039184 DOI: 10.3928/23258160-20210330-03

Background and objectives: To characterize mean number of injections, injection type, and injection frequency during the first year of treatment; assess factors significantly related to injection interval; and identify predictive factors related to patient outcomes.

Patients and methods: A retrospective, noncomparative, nonrandomized cohort study of ocular treatment with intravitreal injections of bevacizumab, ranibizumab, and aflibercept in eyes with neovascular age-related macular degeneration (nAMD). Data from January 1, 2012, through March 31, 2018, were systematically extracted from the electronic medical record system at Cole Eye Institute. Eligible patients had three or more injections within the first 12 months of treatment and received no prior injections.

Results: Patients received an average 8.12 ± 2.45 injections, and 45% of patients received injections at an interval of 8 weeks or less (≤q8 weeks), 33% received injections at 8 to 12 weeks (q8-12 weeks), and 22% received injections at greater than 12 weeks (>q12 weeks). Age (P = .007) and initial central subfield thickness (CST) (P = .043) had statistically significant trend relationships (P = .007) with injection interval, whereas younger patients and patients with higher CST measurements tended to have shorter injection intervals. Injection interval was a significant predictor of visual acuity (VA) and CST. Patients receiving injections at q8-12 weeks were more likely to have better VA outcomes than patients with injection intervals at ≤q8 weeks (odds ratio [OR] = 1.66 [1.16, 2.37]; P = .005). Patients receiving injections at >q12 weeks did not show a significant improvement in VA (P = .06) and were more likely to have worse CST outcomes than patients receiving injections at ≤q8 weeks (OR = 1.95 [1.17, 3.26]; P = .011).

Conclusion: A significant portion of patients receive injections at an interval longer than every 8 weeks. Age and baseline CST had a significant relationship with injection interval. Injection interval was a significant predictor of VA and CST at 1 year. Patients with an injection interval of >q12 weeks tended to have less VA improvement and CST reduction compared to the ≤q8 weeks and q8-12 weeks groups. These findings suggest an extended injection interval >q12 weeks may be at the expense of potential VA improvement.


Transcriptome Analysis of Choroid and Retina From Tree Shrew With Choroidal Neovascularization Reveals Key Signaling Moieties

Front Genet. 2021 May 10;12:654955.

Jie Jia, Dandan Qiu, Caixia Lu, Wenguang Wang, Na Li, Yuanyuan Han, Pinfen Tong, Xiaomei Sun, Min Wu, Jiejie Dai 

PMID: 34040635 PMCID: PMC8141912 DOI: 10.3389/fgene.2021.654955

Pathological neovascularization in choroid, a leading cause of blindness, is a characteristic of many fundus diseases, such as diabetic retinopathy and age-related macular degeneration. The present study aimed to elucidate the key signaling pathways in choroidal neovascularization (CNV) by analyzing the mRNA profiles of choroid and retina in tree shrews with CNV. We induced choroidal angiogenesis by laser photocoagulation in 15 tree shrews and obtained mRNA profiles of their choroids and retinas by high-throughput transcriptome sequencing. Hierarchical cluster analysis, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network analysis, hematoxylin and eosin (HE) staining, CD31 immunohistochemistry (IHC), and reverse transcription quantitative PCR (RT-qPCR) were performed. After laser photocoagulation, we obtained a total of 350 differentially expressed genes (DEGs) in the choroid, including 59 genes in Module-FASN (“ME-FASN”) module and 28 genes in Module-RPL (“ME-RPL”) module. A total of 69 DEGs in retina, including 20 genes in Module-SLC (“ME-SLC”) module. Bioinformatics analysis demonstrated that DEGs in choroid were mainly involved in membrane transport; DEGs in “ME-RPL” were prominent in pathways associated with IgA production, antigen presentation, and cell adhesion molecules (CAMs) signaling. DEGs in “ME-FASN” were involved in fatty acid metabolism and PPAR signaling pathway, while DEGs in “ME-SLC” were involved in GABAergic synapse, neuroactive life receptor interaction, cholinergic synapse, and retrograde endocannabinoid signaling pathway. PPI network analysis demonstrated that the ribosomal protein family genes (RPL31, RPL7, RPL26L1, and RPL19) are key factors of “ME-RPL,” acyl-CoA superfamily genes (ACACA, ACAT1, ACAA2, and ACACB) and FASN are key factors of “ME-FASN” and superfamily of solid carrier genes (SLC17A6, SLC32A1, SLC12A5, and SLC6A1) and complement genes (C4A, C3, and C2) are key factors of “ME-SLC.” In conclusion, the present study discovered the important signal transductions (fatty acid metabolic pathway and CAMs signaling) and genes (ribosomal protein family and the complement system) in tree shrew CNV. We consider that our findings hold implications in unraveling molecular mechanisms that underlie occurrence and development of CNV.


Influence of gut microbiota on eye diseases: an overview

Ann Med. 2021 Dec;53(1):750-761.

Pasquale Napolitano, Mariaelena Filippelli, Sergio Davinelli, Silvia Bartollino, Roberto dell’Omo, Ciro Costagliola  

PMID: 34042554 DOI: 10.1080/07853890.2021.1925150

The microbiota is a dynamic ecosystem that plays a major role in the host health. Numerous studies have reported that alterations in the intestinal microbiota (dysbiosis) may contribute to the pathogenesis of various common diseases such as diabetes, neuropsychiatric diseases, and cancer. However, emerging findings also suggest the existence of a gut-eye axis, wherein gut dysbiosis may be a crucial factor influencing the onset and progression of multiple ocular diseases, including uveitis, dry eye, macular degeneration, and glaucoma. Currently, supplementation with pre- and probiotics appears is the most feasible and cost-effective approach to restore the gut microbiota to a eubiotic state and prevent eye pathologies. In this review, we discuss the current knowledge on how gut microbiota may be linked to the pathogenesis of common eye diseases, providing therapeutic perspectives for future translational investigations within this promising research field.


Genetic associations of central serous chorioretinopathy: a systematic review and meta-analysis

Br J Ophthalmol. 2021 May 26;bjophthalmol-2021-318953.

Zhen Ji Chen, Shi Yao Lu, Shi Song Rong, Mary Ho, Danny Siu-Chun Ng, Haoyu Chen, Bo Gong, Jason C Yam, Alvin L Young, Marten Brelen, Clement C Tham, Chi Pui Pang, Li Jia Chen

PMID: 34039561 DOI: 10.1136/bjophthalmol-2021-318953

Aims: To identify single-nucleotide polymorphisms (SNPs) associated with central serous chorioretinopathy (CSCR) by a systematic review and meta-analysis, and to compare the association profiles between CSCR, neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).

Methods: We searched the EMBASE, PubMed and Web of Science for genetic studies of CSCR from the starting dates of the databases to 12 September 2020. We then performed meta-analyses on all SNPs reported by more than two studies and calculated the pooled OR and 95% CIs. We also conducted sensitivity analysis and adopted the funnel plot to assess potential publication bias.

Results: Totally 415 publications were reviewed, among them 10 were eligible for meta-analysis. We found 10 SNPs that have been reported at least twice. Meta-analysis and sensitivity analysis confirmed significant associations between CSCR and six SNPs in three genes, namely age-related maculopathy susceptibility 2 (ARMS2) (rs10490924, OR=1.37; p=0.00064), complement factor H (CFH) (rs800292, OR=1.44; p=7.80×10-5; rs1061170, OR=1.34; p=0.0028; rs1329428, OR=1.40; p=0.012; and rs2284664, OR=1.36; p=0.0089) and tumour necrosis factor receptor superfamily, member 10a (TNFRSF10A) (rs13278062, OR=1.34; p=1.44×10-15). Among them, only TNFRSF10A rs13278062 showed the same trend of effect on CSCR, nAMD and PCV, while the SNPs in ARMS2 and CFH showed opposite trends in the SNP associations.

Conclusions: This study confirmed the associations of ARMS2, CFH and TNFRSF10A with CSCR, and revealed that ARMS2, CFH and TNFRSF10A may affect different phenotypic expressions of CSCR, nAMD and PCV.


Retina. 2021 May 18.

Prithvi Ramtohul, Michael Engelbert, Ariane Malclès, Edward Gigon, Elisabetta Miserocchi, Giulio Modorati, Eduardo Cunha de Souza, Cagri G Besirli, Christine A Curcio, K Bailey Freund

PMID: 34029276 DOI: 10.1097/IAE.0000000000003217

Purpose: To clarify the histologic basis of bacillary layer detachment (BALAD) through a review of current literature and an analysis of retinal imaging.

Methods: We reviewed the literature for previous reports of BALAD. An analysis of retinal images was performed to support anatomic conclusions.

Results: A total of 164 unique patients with BALAD on optical coherence tomography (OCT) were identified from the published literature. Twenty-two underlying etiologies, all associated with subretinal exudation, were identified. Forty-one different OCT terminologies were found. The defining OCT feature of BALAD was a split at the level of the photoreceptor inner segment myoid creating a distinctive intraretinal cavity. Resolution of BALAD was followed by a rapid restoration of the ellipsoid zone. Histology of age-related macular degeneration eyes suggests that individual photoreceptors can shed inner segments. Further, detachment of the entire layer of inner segments is a common postmortem artefact. We propose that BALAD occurs when outwardly directed forces promoting attachment of photoreceptor outer segments to the retinal pigment epithelium exceed the tensile strength of the photoreceptor inner segment myoid.

Conclusion: Our review serves to strengthen the OCT nomenclature “bacillary layer detachment”, based on specific reflectance information obtained by OCT and previously published histologic observations.