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Optical coherence tomography (OCT) images coupled with many learning techniques have been developed to diagnose retinal disorders. This work aims to develop a novel framework for extracting deep features from 18 pre-trained convolutional neural networks (CNN) and to attain high performance using OCT images. In this work, we have developed a new framework for automated detection of retinal disorders using transfer learning. This model consists of three phases: deep fused and multilevel feature extraction, using 18 pre-trained networks and tent maximal pooling, feature selection with ReliefF, and classification using the optimized classifier. The novelty of this proposed framework is the feature generation using widely used CNNs and to select the most suitable features for classification. The extracted features using our proposed intelligent feature extractor are fed to iterative ReliefF (IRF) to automatically select the best feature vector. The quadratic support vector machine (QSVM) is utilized as a classifier in this work. We have developed our model using two public OCT image datasets, and they are named database 1 (DB1) and database 2 (DB2). The proposed framework can attain 97.40% and 100% classification accuracies using the two OCT datasets, DB1 and DB2, respectively. These results illustrate the success of our model.

Retinal imaging helps to detect retinal and cardiovascular abnormalities. Among these abnormalities, Diabetic Macular Edema (DME) and Age Related Macular Degeneration (AMD), both are frequent retinal degenerative diseases leading to blindness. Content based retinal OCT scan retrieval process makes use of characteristic features to retrieve similar Optical Coherent Tomography (OCT) scans, index-wise, from a database with minimal human intervention. A number of existing methods take care of segmentation and identification of retinal landmarks and pathologies from OCT volumes. As per the literature survey, till date, no papers are there which deal with the retrieval of retinal OCT scans. In this work, we propose a retrieval system for retinal OCT scans which extracts feature maps of both query and database samples from the layer of deep convolutional neural network and compares for their similarity. The Twin network comparison approach exploits deep features without the resource, space and computation exhaustive network training phase. Most of the techniques involving deep network implementation suffer from the drawbacks of data augmentation and resizing. These requirements have been eliminated automatically as part of the Twin network implementation procedure. The system successfully retrieves retinas with similar symptoms from the database of differently affected and unaffected OCT scans. We evaluated different variations of retrieval performances like AMD-Normal, DME-Normal, AMD-DME, AMD-DME-Normal, etc. Execution time optimization has also been achieved as the network used is comparatively shallow and network training is not required. The system retrieves similar scans from a dataset of abnormal and normal OCT scans with a mean average precision of 0.7571 and mean reciprocal rank of 0.9050. Considering all possible variations of retrieval, we achieved overall mean average precision and mean reciprocal rank of 0.631167 and 0.829607, respectively which are also quite notable with rank thresholds of 3, 5 and 7. Experiments show that the method is noticeably successful in retrieving similar OCT volumes. Per image mean average retrieval time is 8.3 sec. Automatic retrieval of retinal OCT volumes for the presence of a particular ailment can help ophthalmologists in the mass screening process. Supplementary Information The online version contains supplementary material available at 10.1007/s12046-021-01701-5.

Objective To develop and validate a questionnaire for the investigation of non-adherence (NA) barriers in patients receiving intravitreal injection (IVT). Design Questionnaire development and cross-sectional patient survey combined with a retrospective medical chart review. Participants German patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) receiving anti-vascular endothelial growth factor (anti-VEGF) treatment via IVT. Methods The previously validated (indications: atrial fibrillation, human immunodeficiency virus, chronic inflammatory lung disease) Adherence Barriers Questionnaire (ABQ) was revised according to specifications of IVT, within the framework of an expert panel. The ABQ-IVT, which initially consisted of 24 items formulated as statements (4-point-Likert-scale ranging from “strongly agree” to “strongly disagree”), was applied in a cross-sectional survey. Evaluation of the questionnaire included an assessment of internal consistency and factor analysis. The occurrence of potential barriers in the patient sample was evaluated using descriptive statistics. To identify patient subpopulations, hierarchical cluster analysis was performed using ABQ-IVT answers as predictors. Due to difficulties in capturing NA as an external criterion, the evaluation of the questionnaire was limited to its internal validity and reliability. Main outcome measures Patients’ answers to the ABQ-IVT questionnaire and interviews. Results Of 253 patients, 234 (92%) were able to complete the ABQ-IVT questionnaire. Within the reliability analysis, the ABQ-IVT was reduced to 17 items. The condensed questionnaire demonstrated good internal consistency (Cronbach’s alpha = 0.78), and factor analysis showed no evidence for subscales of the questionnaire. Nearly half of the patients (49%) reported being affected by at least three different barriers. On average, a patient was affected by 3.1 barriers. The most frequently reported barriers were “Challenge due to time commitment of physician visits” (45% of the patients), “Depression” (29%) and “Travel and opportunity costs” (27%). Cluster analysis identified six patient subpopulations, each affected by different sets of barriers and differed regarding their patient characteristics. Conclusions The ABQ-IVT is a practical and reliable instrument for identifying patient-specific barriers to IVT treatment adherence. In practice, the questionnaire may be useful in assessing whether individual patients are at higher risk of NA due to specific adherence barriers. Aside from better awareness, this allows earlier interventions, though these still need to be validated. Patient subpopulations face different barriers and may, therefore, need distinct preventative care.

Purpose To suggest the safety and efficacy of preservative-free triamcinolone acetonide intravitreal injectable suspension (Taioftal) for the treatment of diabetic macular edema. Methods A prospective clinical study involved 49 patients (49 eyes), that were treated with Taioftal and followed-up for six months. Complete ophthalmic examination, including spectral domain optical coherence tomography, was performed at baseline, and at month 1, 3, 6 after the intravitreal injection. Accurate collection and analysis of best-corrected visual acuity (BCVA), central foveal thickness (CFT), intraocular pressure (IOP), and adverse events (AEs) were carried out in order to evaluate visual function and macular morphology before and after treatment Results Median BCVA value chosen as comparing statistics was significantly improved at every follow-up time points (gain of 6 letters at month 1, 12 at month 3 –improvement up to 24% at month 3 with stabilization until month 6) compared to baseline, as certified by Kruskal-Wallis rank sum test (P Conclusion Intravitreal injection of preservative-free triamcinolone (Taioftal) is an effective, safe and inexpensive drug used to improve visual acuity and reduce central foveal thickness in eyes affected by diabetic macular edema during an average time of 6 months. Temporary, never severe, elevation of IOP is totally manageable with topical medications. No serious vision-threatening complications are related to the use of intravitreal triamcinolone injections.

Objective: Diabetic macular edema (DME) and retinal vein occlusion (RVO) are the leading causes of visual impairments across the world. Vascular endothelial growth factor (VEGF) stimulates breakdown of blood-retinal barrier that causes accumulation of fluid within macula. Anti-VEGF therapy is the first-line treatment for both the diseases; however, the degree of response varies for individual patients. The main objective of this work was to identify the (i) texture-based radiomics features within individual fluid and retinal tissue compartments of baseline spectral-domain optical coherence tomography (SD-OCT) images and (ii) the specific spatial compartments that contribute most pertinent features for predicting therapeutic response. Methods: A total of 962 texture-based radiomics features were extracted from each of the fluid and retinal tissue compartments of OCT images, obtained from the PERMEATE study. Top-performing features selected from the consensus of different feature selection methods were evaluated in conjunction with four different machine learning classifiers: Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), Random Forest (RF), and Support Vector Machine (SVM) in a cross-validated approach to distinguish eyes tolerating extended interval dosing (non-rebounders) and those requiring more frequent dosing (rebounders). Results: Combination of fluid and retinal tissue features yielded a cross-validated area under receiver operating characteristic curve (AUC) of 0.78±0.08 in distinguishing rebounders from non-rebounders. Conclusions: This study revealed that the texture-based radiomics features pertaining to IRF subcompartment were most discriminating between rebounders and non-rebounders to anti-VEGF therapy. Clinical Impact: With further validation, OCT-based imaging biomarkers could be used for treatment management of DME patients.

We evaluated the impact of the COVID-19 pandemic on anti-VEGF treatment in ophthalmology patients in a single hospital in northern China. A total of 93 anti-VEGF injections were administered to 85 eyes of 72 patients at The China Medical University First Hospital Department of Ophthalmology during the COVID-19 pandemic. Compared to the same period in 2019, the number of injections decreased by 70%. Fifty-nine eyes of 46 patients were receiving 3+PRN anti-VEGF treatment prior to the outbreak of the COVID-19 pandemic; all of these patients experienced treatment interruptions due to COVID-19-associated reasons. Anatomic and functional outcomes suggest that patients with anti-VEGF treatment interruptions are at risk for severe adverse visual sequelae. Moreover, deferred anti-VEGF treatment due to patient-related or department-related reasons during the COVID-19 pandemic may result in poor visual outcomes for new patients. Our results suggest that COVID-19 has had a significant negative effect on anti-VEGF treatment in ophthalmology patients. Detailed guidance from global experts in ophthalmology is highly sought after in these challenging circumstances.

Disruption of retinal pigment epithelial (RPE barrier integrity is a hallmark feature of various retinal blinding diseases, including diabetic macular edema and age-related macular degeneration, but the underlying causes and pathophysiology are not completely well-defined. One of the most conserved phenomena in biology is the progressive decline in mitochondrial function with aging leading to cytopathic hypoxia, where cells are unable to use oxygen for energy production. Therefore, this study aimed to thoroughly investigate the role of cytopathic hypoxia in compromising the barrier functionality of RPE cells. We used Electric Cell-Substrate Impedance Sensing (ECIS) system to monitor precisely in real time the barrier integrity of RPE cell line (ARPE-19) after treatment with various concentrations of cytopathic hypoxia-inducing agent, Cobalt(II) chloride (CoCl2). We further investigated how the resistance across ARPE-19 cells changes across three separate parameters: Rb (the electrical resistance between ARPE-19 cells), α (the resistance between the ARPE-19 and its substrate), and Cm (the capacitance of the ARPE-19 cell membrane). The viability of the ARPE-19 cells and mitochondrial bioenergetics were quantified with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and seahorse technology, respectively. ECIS measurement showed that CoCl2 reduced the total impedance of ARPE-19 cells in a dose dependent manner across all tested frequencies. Specifically, the ECIS program’s modelling demonstrated that CoCl2 affected Rb as it begins to drastically decrease earlier than α or Cm, although ARPE-19 cells’ viability was not compromised. Using seahorse technology, all three concentrations of CoCl2 significantly impaired basal, maximal, and ATP-linked respirations of ARPE-19 cells but did not affect proton leak and non-mitochondrial bioenergetic. Concordantly, the expression of a major paracellular tight junction protein (ZO-1) was reduced significantly with CoCl2-treatment in a dose-dependent manner. Our data demonstrate that the ARPE-19 cells have distinct dielectric properties in response to cytopathic hypoxia in which disruption of barrier integrity between ARPE-19 cells precedes any changes in cells’ viability, cell-substrate contacts, and cell membrane permeability. Such differences can be used in screening of selective agents that improve the assembly of RPE tight junction without compromising other RPE barrier parameters.

Purpose To evaluate macular function and structure in patients with diabetic macular edema prior to, as well as 3 and 6 months after intravitreal ranibizumab treatment. Patients and methods Seventeen eyes of 17 patients with type 2 diabetes mellitus and diabetic macular edema (DME) were treated with intravitreal injections of 0.5 mg ranibizumab. Prior to the first injection, as well as after 3 and 6 months, the following examinations were performed: assessment of distance best-corrected visual acuity (log MAR), perception of metamorphopsia (M-Chart), slit lamp examination of the anterior and posterior segment of the eye (Volk 90D lens), evaluation of the retinal and choroidal circulation (fluorescein angiography), assessment of the structure and thickness of the macula (OCT), as well as evaluation of the macular function (PERG and mfERG). Results We observed that ranibizumab significantly improved visual acuity after 3 and 6 months from the beginning of the treatment, which was a consequence of reduced macular edema and vascular leakage. There was a statistically significant decrease in metamorphopsia frequency at month 3; however, at month 6 it was a statistically insignificant when compared to the baseline. The results of electrophysiological examinations revealed no improvement in ranibizumab-treated patients. Conclusion Improvement of visual acuity and reduction in macular thickness were maintained up to the 6-month follow-up. The results of electrophysiological examinations revealed that ranibizumab injections tend to stabilize bioelectrical macular function of the outer, middle and inner retinal layers, which was impossible to recognize on the basis of visual acuity and OCT. Therefore, the electrophysiological examinations should be used as an additional objective tool for the evaluation of the anti-VEGF treatment effectiveness in DME.

The aim of this work was to investigate the changes in aqueous humor cytokine levels after intravitreal injection of aflibercept in diabetic macular edema (DME) and to evaluate the relationship between cytokines modifications and central macular thickness (CMT) and retinal/choroidal vascular changes using structural and functional optical coherence tomography (OCT). Aqueous concentrations of 38 cytokines were measured via multiplex bead assay. In addition, spectral domain OCT and OCT angiography with SSADA software (XR Avanti® AngioVue) were performed at baseline and after intravitreal injections. VEGF, IL-6, IL-5, IL-1β, Eotaxin, GRO, IL-12p40, IL-12p70, IL-1RA, Flt-3L and IP-10 showed a statistically significant decrease through the follow-up (p

Objective: To compare the efficacy of intravitreal triamcinolone acetonide (IVTA) and IVTA plus macular laser grid photocoagulation therapy in diffuse diabetic macular edema (DME). Material and Methods: Sixteen patients affected by diffuse DME were retrospectively evaulated. Patients were divided into two groups: control group (IVTA injection) and laser group (IVTA plus grid laser). Main outcomes were best corrected visual aquity (BCVA) and central macular thickness (CMT) at the 3rd and 6th months of treatment. IVTA associated complications and reinjection necessity were assessed. Results: Our study comprised 18 eyes of 16 patients. The baseline BCVA and CMT were 0.93±0.45 and 530±136μm for the control and 1.02±0.52 and 509±177μm for the laser group respectively. Posttreatment BCVA at the 3rd and 6th month were 0.73±0.4 and 0.75±0.45 for control and 0.98±0.44 and 1.04±0.4 for laser group respectively (p>0.05 for all). CMT values at the 3rd and 6th months were 260±174μm (p=0.008) and 362±163 μm (p=0.05) for control and 331±161μm (p=0.05) and 388±215 μm (p>0.05) for laser groups. 55% of control and 66% of laser groups needed reinjection with an avarage of 7±4 months after the first injection. 22% cataract progression and 33% intraocular pressure elevation were noted. Conclusion: Macular grid laser photocoagulation after IVTA does not have beneficial effects for diffuse DME. Turkish Başlık: Diffüz Diabetik Maküler Ödemli Hastalarda İntravitreal Triamsinolon Tedavisi İle İntravitreal Triamsinolon ve Grid Lazer Tedavisinin Karşılaştırılması Anahtar Kelimeler: Diabetik maküler ödem, İntravitreal triamsinolon, grid lazer Amaç: Diffüz diabetik maküla ödeminde (DMÖ), intravitreal triamsinolon asetonid (İVTA) ve İVTA'ya ek maküler lazer grid fotokoagülasyon tedavisinin etkinliğini karşılaştırmak. Materyal-Metod: Diffüz DME mevcut 16 hasta retrospektif olarak değerlendirildi. Hastalar iki gruba ayrıldı: kontrol grubu (İVTA enjeksiyonu) ve lazer grubu (İVTA artı grid lazer). Tedavinin 3. ve 6. ayındaki en iyi düzeltilmiş görme keskinliği (DGK) ve santral maküler kalınlık (SMK) değerlendirildi. Aynı zamanda İVTA ile ilişkili komplikasyonlar ve tekrarlayan enjeksiyon gereksinimi değerlendirildi. Sonuçlar: Çalışmamızda 16 hastanın 18 gözü değerlendirilmiştir. Başlangıç DGK ve SMK sırasıyla kontrol grubunda 0.93±0.45 ve 530±136µm ve lazer grubunda 1.02±0.52 and 509±177µm idi. Tedavi sonrası DGK, 3. ve 6. ayda sırasıyla kontrol grubunda 0.73±0.4 and 0.75±0.45 ve lazer grubunda 0.98±0.44 and 1.04±0.4 idi (tüm değerler için p˃0.05). 3. ve 6. ayda SMK değerleri, kontrol grubunda 260±174µm (p=0.008) ve 362±163µm (p=0.05) ve lazer grubunda 331±161µm (p=0.05) ve 388±215µm (p˃0.05) idi. Kontrol grubunun %55'inde ve lazer grubunun %66'sında ilk enjeksiyondan ortalama 7±4 ay sonra ek enjeksiyon gerekmiştir. %22 katarakt gelişimi ve %33 göziçi basınç artışı izlendi. Tartışma: Diffüz diabetik maküla ödeminde İVTA enjeksiyonu sonrası uygulanan maküler grid lazer fotokoagülsayonun ek faydasının olmadığı izlenmiştir.

Throughout the years, people with diabetic macular oedema (DMO) have seen the number of options for their treatment increasing. Laser photocoagulation was the first of these and great experience is behind it; intraocular steroids followed and more recently anti-vascular endothelial growth factor (anti- VEGF) agents came to light. Ophthalmologists face now the dilemma of determining which may be the best therapeutic strategy for each particular patient based on best available evidence. This article summarises data available from randomised clinical trials (RCTs) on treatments for DMO and provides some facts about this condition and its treatments that need to be taken into consideration when treatment decisions are made.

Background This was an indirect comparison of the effectiveness of intravitreal aflibercept (IVT-AFL) 2 mg every 8 weeks after 5 initial monthly doses (or if different periods, after an initial monthly dosing period) (2q8) and other diabetic macular edema (DME) therapies at doses licensed outside the USA. Methods A comprehensive search was undertaken to source relevant studies. Feasibility networks were prepared to identify viable comparisons of 12-month outcomes between IVT-AFL 2q8 and therapies licensed outside the USA, which were assessed for clinical and statistical homogeneity. Pooled effect sizes (mean difference [MD] and relative risk/risk ratio [RR]) were calculated using fixed- and random-effects models. Indirect comparisons were performed using Bucher analysis. If at least one ‘head-to-head’ study was found then a mixed treatment comparison (MTC) was performed using Bayesian methods. Two 12-month comparisons could be undertaken based on indirect analyses: IVT-AFL 2q8 versus intravitreal ranibizumab (IVR) 0.5 mg as needed (PRN) (10 studies) and IVT-AFL 2q8 versus dexamethasone 0.7 mg implants (three studies). Results There was an increase in mean best-corrected visual acuity (BCVA) with IVT-AFL 2q8 over IVR 0.5 mg PRN by 4.67 letters [95% credible interval (CrI): 2.45–6.87] in the fixed-effect MTC model (10 studies) and by 4.82 letters [95% confidence interval (CI): 2.52–7.11] in the Bucher indirect analysis (four studies). IVT-AFL 2q8 doubled the proportion of patients gaining ≥ 10 Early Treatment Diabetic Retinopathy Study letters at 12 months compared with dexamethasone 0.7 mg implants (RR = 2.10 [95% CI: 1.29–3.40]) in the fixed-effect model. There were no significant differences in safety outcomes between IVT-AFL 2q8 and IVR 0.5 mg PRN or dexamethasone 0.7 mg implants. Conclusions Studies of IVT-AFL 2q8 showed improved 12-month visual acuity measures compared with studies of IVR 0.5 mg PRN and dexamethasone 0.7 mg implants based on indirect comparisons. These analyses are subject to a number of limitations which are inherent in indirect data comparisons. Electronic supplementary material The online version of this article (doi:10.1186/s12886-015-0035-x) contains supplementary material, which is available to authorized users.

Objective: To assess the effectiveness of intravitreal injection of Bevacizumab in the treatment of diabetic macular edema. Methods: This case series was conducted at Department of Ophthalmology, Jinnah Post Graduate Medical Centre (JPMC), Karachi. The duration of study was six months from May 26, 2011 to November 25, 2011. The study group comprised of 54 patients of the Diabetic Macular Edema (DME). Intravitreal injection of 1.25 mg of bevacizumab (Avastin) was injected 3.5 mm from the limbus under topical anaesthetic drops. Post procedure follow up was scheduled on 1st post procedure day and after one month. Post procedure Optical Coherence tomography (OCT) was performed in all patients 1 week before and 1st month after 1st injection. The results were statistically analyzed through SPSS 17. Results: Out of the 54 Eyes of 54 Patients who were given the Intravitreal injection of Avastin (Bevacizumab), 43 Eyes (79.6%) showed more than ten percent decrease in macular thickness from pre-injection thickness, 10 Eyes (18.5%) showed less than ten percent decrease and 1 Eye (1.9%) showed increase in macular thickness post operatively after one month. Conclusions: Intravitreal injection of Bevacizumab (Avastin) is effective in the treatment of diabetic macular edema.

Objective: To evaluate the efficacy of primary intra vitreal bevacizumab (IVB) injection on macular edema in diabetic patients with improvement in best corrected visual acuity (BCVA) and central macular thickness (CMT) on optical coherence tomography (OCT). Methods: This prospective interventional case series study was conducted at Retina Clinic, Al-Ibrahim Eye Hospital, and Isra Postgraduate Institute of Ophthalmology Karachi. Between December 2010 to June 2012. BCVA measurement with Early Treatment in Diabetic Retinopathy Study (ETDRS) charts and ophthalmic examination, including Slit-lamp bio microscopy, indirect ophthalmoscopy, Fundus fluorescein angiography (FFA) and OCT were done at the base line examination. At monthly interval all patients were treated with 3 injections of 0.05 ml intra vitreal injection containing 1.25 mg bevacizumab. Patients were followed up for 6 months and BCVA and OCT were taken at the final visit at 6 month. Results: The mean BCVA at base line was 0.42±0.14 Log Mar units. This improved to 0.34±0.13, 0.25±0.12, 0.17±0.12 and 0.16±0.14 Log Mar units at 1 month after 1 st , 2 nd 3 rd injections and at final visit at 6 months respectively, a difference that was statistically significant (P > 0.0001) from base line. The mean 1mm CMT measurement was 452.9 ± 143.1 µm at base line, improving to 279.8 ± 65.2 µm (P < 0.0001) on final visit. No serious complications were observed. Conclusions: Primary IVB at a dose of 1.25 mg on monthly interval seems to provide stability and improvement in BCVA and CMT in patient with DME.