Diabetic macular oedema (DMO) is the major cause of visual impairment in people with diabetes. Optical coherence tomography (OCT) is now the most widely used modality to assess presence and severity of DMO. DMO is currently broadly classified based on the involvement to the central 1 mm of the macula into non-centre or centre involved DMO (CI-DMO) and DMO can occur with or without visual acuity (VA) loss. This classification forms the basis of management strategies of DMO. Despite years of research on quantitative and qualitative DMO related features assessed by OCT, these do not fully inform physicians of the prognosis and severity of DMO relative to visual function. Having said that, recent research on novel OCT biomarkers development and re-defined classification of DMO show better correlation with visual function and treatment response. This review summarises the current evidence of the association of OCT biomarkers in DMO management and its potential clinical importance in predicting VA and anatomical treatment response. The review also discusses some future directions in this field, such as the use of artificial intelligence to quantify and monitor OCT biomarkers and retinal fluid and identify phenotypes of DMO, and the need for standardisation and classification of OCT biomarkers to use in future clinical trials and clinical practice settings as prognostic markers and secondary treatment outcome measures in the management of DMO.

Different network meta-analyses (NMAs) on the same topic result in differences in findings. In this review, we investigated NMAs comparing aflibercept with ranibizumab for diabetic macular oedema (DME) in the hope of illuminating why the differences in findings occurred.
Studies were searched for in English and Chinese electronic databases (PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP; see detailed search strategy in the main body). Two independent reviewers systematically screened to identify target NMAs that included a comparison of aflibercept and ranibizumab in patients with DME. The key outcome of interest in this review is the change in best-corrected visual acuity (BCVA), including various ways of reporting (such as the proportion of participants who gain ≥ 10 ETDRS letters at 12 months; average change in BCVA at 12 months).
For the binary outcome of BCVA, different NMAs all agreed that there is no clear difference between the two treatments, while continuous outcomes all favour aflibercept over ranibizumab. We discussed four points of particular concern that are illustrated by five similar NMAs, including network differences, PICO (participants, interventions, comparators, outcomes) differences, different data from the same measures of effect, and differences in what is truly significant.
A closer inspection of each of these trials shows how the methods, including the searches and analyses, all differ, but the findings, although presented differently and sometimes interpreted differently, were similar.

OBJECTIVE: To evaluate the short-term effect of intravitreal bevacizumab (avastin) injection on visual outcomes of patients with diabetic macular oedema.
METHODS: A retrospective cross-sectional study was conducted to evaluate 39 eyes of thirty-nine patients (mean age ± SD: 61.4 ± 15.0 years) that received intravitreal bevacizumab injection (1.25 mg in 0.05 ml) as treatment for diabetic macular oedema between January 2014 and July 2019 in Ghana. Data on visual acuity and central macular thickness before treatment and 6 weeks post-treatment were collected and analysed using paired t-test. Ordinary least squares linear regression analysis was also conducted to determine the relationship between improvement in visual acuity and central macular thickness after treatment and other predictor variables.
RESULTS: The mean ± SD visual acuity (LogMAR-equivalent of Snellen) of patients with diabetic macular oedema significantly improved from 0.84 ± 0.58 LogMAR before treatment to 0.69 ± 0.58 LogMAR at 6 weeks post-treatment (mean difference: 0.15 ± 0.32 LogMAR; 95% CI: 0.04 to 0.25; p = 0.01). Mean macular thickness ± SD on the other hand, reduced significantly (p < 0.001) from 316.54 ± 75.35 μm before treatment to 275.54 ± 57.43 μm after treatment. While age and worse pre-treatment visual acuity predicted improvement in visual acuity after treatment, a higher central macular thickness before treatment predicted an improvement in central macular thickness after intravitreal bevacizumab injection.
CONCLUSIONS: Treatment with intravitreal bevacizumab injection produces short-term improvement in vision and reduction in central macular thickness in African patients with diabetic macular oedema.

Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness among diabetics. We aimed to explore whether long-term exposure to residential greenness was beneficial to DR.
We used data from a large-scale, cross-sectional screening survey conducted in 129 cities of 27 provincial regions of China from 2018 to 2021 among patients with diabetes. We measured residential greenness exposure as the 3-year average of annual maximum Normalized Difference Vegetation Index (NDVI) at a spatial resolution of 250 m. DR was assessed by ophthalmologists based on fundus photographs. The primary outcome was DR, and secondary outcome included DR severity status (i.e., nonproliferative and proliferative), hallmarks of retinal lesions and macular oedema.
A total of 484,380 adult participants with diabetes were included in the current analysis, and 15.7% of them were diagnosed with DR. NDVI was inversely and linearly associated with DR prevalence, and an increment of 0.1 NDVI was associated with a 10% (9%-10%) decrease in DR prevalence. Significant and inverse associations were further found for nonproliferative and proliferative DR, hallmarks of lesions and macular oedema. The association between greenness and DR was stronger among participants who were older, obese, lived in the south, had longer duration of diabetes or did not take antidiabetic medications.
This large-scale nationwide study provides the first-hand epidemiological evidence on the associations of residential greenness with DR. Our findings highlight the importance of residential greenness in alleviating DR risk especially in an era of aging and urbanization.

OBJECTIVE: In eyes with diabetic macular oedema (DME), aqueous humour (AH) cytokine levels before and after anti-vascular endothelial growth factor (VEGF) treatment were compared and correlated with optical coherence tomography structural parameters.
METHODS: This prospective study included 56 control patients with cataracts and 83 patients with DME manifesting as diffuse retinal thickening (DRT), cystoid macular oedema and serous retinal detachment (SRD). AH samples were obtained before intravitreal injection of anti-VEGF or cataract surgery. VEGF, interleukin (IL)-6, IL-8, IL-10, interferon-inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1) levels were measured by multiplex bead assay. AH cytokine levels, central macular thickness (CMT), number of hyper-reflective foci (HF), continuity of external limiting membrane and ellipsoid zone (EZ) and best-corrected visual acuity were evaluated.
RESULTS: In SRD, IL-6 and MCP-1 levels and HF were increased (all p < 0.05) compared to DRT. At baseline, the number of HF was correlated with VEGF, IL-6, IL-8, IP-10 and MCP-1 (all p < 0.05). Eyes sensitive to anti-VEGF treatment had high baseline levels of VEGF, MCP-1, HF and many EZ disruptions (all p < 0.05). DME patients with normal VEGF levels but with high levels of IL-8, IP-10 and MCP-1 (all p < 0.05) had little change in CMT after anti-VEGF treatment (p = 0.678).
CONCLUSIONS: AH concentrations of some inflammatory cytokines in DME were differentially expressed among the three DME morphologies. HF was associated with VEGF and other inflammatory cytokine levels. Multiple HF at baseline predicted a significant decrease in CMT, and eyes with normal VEGF but increased inflammatory cytokines may be insensitive to anti-VEGF treatment.

OBJECTIVE: To predict the anti-vascular endothelial growth factor (VEGF) therapeutic response of diabetic macular oedema (DME) patients from optical coherence tomography (OCT) at the initiation stage of treatment using a machine learning-based self-explainable system.
METHODS: A total of 712 DME patients were included and classified into poor and good responder groups according to central macular thickness decrease after three consecutive injections. Machine learning models were constructed to make predictions based on related features extracted automatically using deep learning algorithms from OCT scans at baseline. Five-fold cross-validation was applied to optimize and evaluate the models. The model with the best performance was then compared with two ophthalmologists. Feature importance was further investigated, and a Wilcoxon rank-sum test was performed to assess the difference of a single feature between two groups.
RESULTS: Of 712 patients, 294 were poor responders and 418 were good responders. The best performance for the prediction task was achieved by random forest (RF), with sensitivity, specificity and area under the receiver operating characteristic curve of 0.900, 0.851 and 0.923. Ophthalmologist 1 and ophthalmologist 2 reached sensitivity of 0.775 and 0.750, and specificity of 0.716 and 0.821, respectively. The sum of hyperreflective dots was found to be the most relevant feature for prediction.
CONCLUSIONS: An RF classifier was constructed to predict the treatment response of anti-VEGF from OCT images of DME patients with high accuracy. The algorithm contributes to predicting treatment requirements in advance and provides an optimal individualized therapeutic regimen.

Long-term stability in plasma glucose may affect the development of diabetic retinopathy (DR) and diabetic macular oedema (DMO).
To investigate the associations between glycaemic variability and the development of DR and DMO in type 2 diabetes (T2D).
An 8-year prospective cohort study.
2005 patients with T2D.
DR and DMO were detected with non-mydriatic fundus photography.
The visit-to-visit variability of fasting glucose or HbA1c was calculated as the standard deviation (SD) or coefficient of variation (CV = SD/mean) of all records during the follow-up periods or before the onset of the targeted event. Cox regression analysis was used to evaluate the hazard ratios (HRs) for new-onset DR, proliferative diabetic retinopathy (PDR), and DMO.
After adjusting for the baseline and mean follow-up values, the SD and CV of fasting glucose during the follow-up periods were both correlated with the development of PDR (SD: HR = 1.011, P = .005; CV: HR = 6.858, P < .001), and DMO (SD: HR = 1.008, P = .038; CV: HR = 4.027, P = .017). As for HbA1c, neither the SD nor CV was correlated with the development of DR, PDR, or DMO (P > .05 for all).
High visit-to-visit fasting glucose variability was associated with new-onset PDR and DMO, independent of baseline and mean follow-up fasting glucose and HbA1c in T2D. Long-term stability in plasma glucose is important for reducing the risk of the development and progression for DR and DMO.

OBJECTIVE: This study aimed to investigate the concentrations of cytokines and chemokines in diabetic macular edema (DME) eyes before and during therapy with the intravitreal injection of conbercept (IVC) and to identify associations with disease activity.
METHODS: The Bio-Plex® 200 System and the Bio-PlexTM Human Cytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) were used to detect cytokine levels in aqueous humour. Experimental aqueous humour samples were collected from 18 patients with DME at the same time that IVC was performed at baseline and at 1 month. Control aqueous humour samples were collected from 16 patients undergoing cataract surgery.
RESULTS: Significantly higher concentrations of vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), IL-8, eotaxin, granulocyte colony stimulating factor (G-CSF), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) were found in the aqueous humour of DME patients than cataract patients. One month after IVC, the intraocular concentrations of VEGF were significantly lower in the eyes of DME patients than at baseline. No other cytokines were significantly altered by conbercept therapy. Best-corrected visual acuity (BCVA) slightly improved following IVC compared with that at baseline, although this difference was not significant, and central macular thickness (CMT) significantly decreased 1 month after IVC treatment.
CONCLUSIONS: Angiogenic, inflammatory and growth factors are involved in the development of DME. With the exception of VEGF, IVC did not cause significant differences in any inflammatory cytokines or growth factors in DME patients. CMT is related to VEGF levels in aqueous humour.

The association of diabetic retinopathy (DR) and diabetic macular oedema (DME) with renal function in southern Chinese patients with diabetes is poorly understood. So we aimed to study the correlation between stage of DR and DME with stage of estimated glomerular filtration rate (eGFR) and stage of urine albumin-to-creatinine ratio (UACR), and to explore the systemic risk factors for DR and DME.
This single-centre retrospective observational study was conducted from December 2017 to November 2018.
413 southern Chinese patients with type 2 diabetes mellitus.
The correlations between stage of DR and DME with stage of eGFR/UACR were assessed by Spearman\'s or χ² analyses and represented with histograms. Risk factors associated with the occurrence of DR and DME were performed by logistic regression and represented with nomograms.
Stage of DR had a positive correlation with stage of eGFR (r=0.264, p<0.001) and stage of UACR (r=0.542, p<0.001). With the stage of eGFR/UACR being more severe, the prevalence of DME became higher as well (both p<0.001). The risk factors for DR were DM duration (OR 1.072; 95% CI 1.032 to 1.114; p<0.001), stage of UACR (OR 2.001; 95% CI 1.567 to 2.555; p<0.001) and low-density lipoprotein (LDL) (OR 1.301; 95% CI 1.139 to 1.485; p<0.001), while risk factors for DME were stage of UACR (OR 2.308; 95% CI 1.815 to 2.934; p<0.001) and LDL (OR 1.460; 95% CI 1.123 to 1.875; p=0.008).
Among southern Chinese patients, stage of DR and DME were positively correlated with renal function, while stage of UACR performed a better relevance than stage of eGFR.

Region-specific pathology in proliferative diabetic retinopathy enhances our understanding and management of this disease.
To investigate non-perfusion, neovascularization and macular oedema.
A cross-sectional, observational, non-randomized study.
Consecutive 43 eyes of 27 treatment-naïve patients.
Ultra-widefield fluorescein angiography for studying specific zones, that is, far-peripheral zone, mid-peripheral zone and central retina (cr), and spectral-domain optical coherence tomography for analysing thickness of macular layers.
Non-perfusion index (NPI) and neovascularization index (NVI) in different zones, thickness of cr, retinal nerve fibre layer, ganglion cell layer (GCL), inner nuclear layer (INL) and outer plexiform layer in parafoveal regions.
The NPI of far-periphery and NVI of mid-periphery were the highest by one-way analysis of variance testing. Ischemic retina defined as high NPI in far-periphery was significantly related to macular oedema via a binary classification approach (P < 0.05). The ischemic retina was correlated with a decreased thickness of both retinal nerve fibre and GCL (P < 0.05); macular oedema was correlated with increased INL thickness (P < 0.0001).
The region-specific correlation of NPI of far-periphery and NVI of mid-periphery, but not with central retinal thickness, suggests different pathogeneses of neovascularization and macular oedema. Retinal nerve fibre layer and GCL, both biomarkers of diabetic retinal neuronopathy, are associated with retinal ischemia, but not with macular oedema, suggesting that diabetic microangiopathy and neuronopathy possess distinct pathogenic pathways. The strong correlation between macular oedema and INL indicates that intracellular oedema is a determining factor of diabetic macular oedema.