Advanced Diabetic Retinopathy Research Articles

Deciphering the connection between microvascular damage and neurodegeneration in early diabetic retinopathy.

Diabetic retinopathy (DR), a common diabetes complication leading to vision loss, presents early clinical signs linked to retinal vasculature damage, affecting the neural retina at advanced stages. However, vascular changes and potential effects on neural cells before clinical diagnosis of DR are less well understood. To study the earliest stages of DR we performed histological phenotyping and quantitative analysis on postmortem retinas from 10 donors with diabetes and without signs of DR (such as microaneurysms and haemorrhages), plus 3 controls and 1 DR case, focusing on capillary loss in the deeper (DVP) and superficial vascular plexuses (SVP) and neural retina effects. The advanced DR case exhibited profound vascular and neural damage, whereas the ten randomly selected donors with diabetes appeared superficially normal. The SVP was indistinguishable from the controls. In contrast, over half of the retinas from donors with diabetes showed capillary dropout in the DVP and increased capillary diameter. However, we could not detect any localised neural cell loss in the vicinity of dropout capillaries. Instead, we observed a subtle pan-retinal loss of inner nuclear layer (INL) cells in all diabetes cases (p<0.05), independent of microvascular damage. In conclusion, our findings demonstrate a novel histological biomarker for early-stage diabetes-related damage in human postmortem retina, common in people with diabetes before clinical DR diagnosis. Furthermore, the mismatch between capillary dropout and neural loss questions the notion of microvascular loss directly causing neurodegeneration at the earliest stages of DR, so diabetes may affect the two readouts independently.

Blue Wavelength of Scanning Laser Ophthalmoscope Potentially Detects Arteriosclerotic Lesions in Diabetic Retinopathy

(1) Background: The fundus examination is one of the best and popular methods in the assessment of vascular status in the human body. Direct viewing of retinal vessels by ophthalmoscopy has been utilized in judging hypertensive change or arteriosclerosis. Recently, fundus imaging with the non-mydriatic scanning laser ophthalmoscope (SLO) has been widely used in ophthalmological clinics since it has multimodal functions for optical coherence tomography or angiography with contrast agent dye. The purpose of this study was to examine the utility in detecting arteriosclerosis of retinal vessels in SLO images; (2) Methods: Both color and blue standard field SLO images of eyes with diabetic retinopathy (DR) were examined retrospectively. Retinal arteriosclerosis in color SLO images was graded according to the Scheie classification. Additionally, characteristics of retinal arterioles in blue SLO images were identified and examined for their relevance to arteriosclerosis grades, stages of DR or general complications; (3) Results: Relative to color fundus images, blue SLO images showed distinct hyper-reflective retinal arterioles against a monotone background. Irregularities of retinal arterioles identified in blue SLO images were frequently observed in the eyes of patients with severe arteriosclerosis (Grade 3: 79.0% and Grade 4: 81.8%). Furthermore, the findings on arterioles were more frequently associated with the eyes of DR patients with renal dysfunction (p &lt; 0.05); (4) Conclusions: While color SLO images are equally as useful in assessing retinal arteriosclerosis as photography or ophthalmoscopy, the corresponding blue SLO images show arteriosclerotic lesions with high contrast in a monotone background. Retinal arteriosclerosis in eyes of advanced grades or advanced DR frequently show irregularities of retinal arterioles in the blue images. The findings of low, uneven, or discontinuous attenuation were easier to find in blue than in color SLO images. Consequently, blue SLO images can show pathological micro-sclerosis in retinal arterioles and are potentially one of the safe and practical methods for the vascular assessment of diabetic patients.

Omega-3-Index bei Patient*innen mit schweren diabetischen Augenkomplikationen

Summary Background The aim of the study was to assess the omega‑3 index and the proportions of other relevant fatty acids (FAs) in patients undergoing vitrectomy due to severe diabetic ocular complications. According to evidence, an optimal omega‑3 index range is 8–11% and a high level of saturated FAs correlate with advanced diabetic retinopathy (DR). Methods Patients with diabetes mellitus (DM) undergoing vitrectomy due to diabetic macular edema or vitreous hemorrhage secondary to proliferative DRP were recruited for this study. Prior to surgery, the omega‑3 index, defined as the proportion of omega‑3 FAs in the membranes of erythrocytes, and the proportions of omega‑6, omega‑9, saturated and trans FAs were assessed using “high-sensitivity” gas chromatography with flame ionization detection. Results In total, 12 patients with DM type 1 (n = 2) and type 2 (n = 10) were enrolled. Their age was 69 ± 12 years and their HbA1c averaged 7.6 ± 1.2%. The omega‑3 index was 4.5 ± 1.2%. There was a moderate negative correlation between HbA1c and the omega‑3 index (r = −0.51, p = 0.09). The proportions of other FAs were within the normal ranges. However, the proportions of omega‑6 and saturated FAs were in the upper range (33.3 ± 2.2% and 41.1 ± 1.3%, respectively). Conclusion Patients with severe diabetic ocular complications who require vitreoretinal surgery are generally under-supplied with omega‑3 FAs and over-supplied with omega‑6 and saturated FAs. Patients with diabetes might consequently benefit from early omega‑3 FA supplementation and a reduction of saturated FAs in order to prevent or at least slow down the development of DRP and ultimately preserve vision.

New Approaches to Surgical Treatment of Patients with Advanced Stage of Proliferative Diabetic Retinopathy

Purpose. Development and evaluation of the clinical effectiveness and safety of a vitrectomy (VE) technique for patients with advanced stage proliferative diabetic retinopathy (ASPDR).Materials and methods. We observed 132 patients (mean age 62.8 ± 2.4 years) with the following criteria for inclusion in the study, corresponding to the classification criteria of ASPDR: it is impossible to estimate the area of neovascularization; the fundus of the eye is partially ophthalmoscoped or not ophthalmoscoped in the posterior pole; preretinal or vitreal hemorrhage in the posterior pole with an area of more than 4 optic discs; retinoschisis in the macular zone. All patients were divided into the following two groups, equal in age, gender and visual status of the “healthy” eye: the main group (MG, 69 patients, 69 eyes), who underwent VE was performed according to the developed method and a control group (CG, 63 patients, 63 eyes), in which VE was performed according to the traditional method.Results. The incidence of intraoperative complications in patients in the MG (5.8 %) was 8.1 % (p &lt; 0.05) lower than in the CG (13.9 %). The incidence of postoperative complications in patients from the MG (5.5 ± 0.5 %) was 4.2 % (p &lt; 0.01) lower than in the CG (9.7 ± 1.0 %). The increase in best-corrected visual acuity after surgery in patients from the MG was significantly (by 0.13 rel. units, p &lt; 0.001) higher than in the CG. The value of the average decrease in the developed qualitative criteria for the condition of the fundus in patients in the MG (1.6 ± 0.1) was 23.1 % (p &lt; 0.05), higher than in the CG (1.3 ± 0.1).Conclusion. Surgical treatment of patients with ASPDR using the developed technique provides (compared to the traditional approach) a higher level of safety and clinical effectiveness. The main advantage of the developed technique is an integrated approach to surgical intervention, including the improvement of ophthalmological “techniques” (use of one-stage combined surgery, endolaser coagulation technology, etc.) and drug support (administration of ranibizumab at a dose of 0.05 mg 3–5 days before surgery) and the choice of intravenous sedation as the optimal anesthetic aid.

Assessing Diabetic Retinopathy Staging With AI: A Comparative Analysis Between Pseudocolor and LED Imaging.

To compare the diagnostic performance of artificial intelligence (AI)-based diabetic retinopathy (DR) staging system across pseudocolor, simulated white light (SWL), and light-emitting diode (LED) camera imaging modalities. A cross-sectional investigation involved patients with diabetes undergoing imaging with an iCare DRSplus confocal LED camera and an Optos confocal, ultra-widefield pseudocolor camera, with and without SWL. Macula-centered and optic nerve-centered 45 × 45-degree photographs were processed using EyeArt v2.1. Human graders established the ground truth (GT) for DR severity on dilated fundus exams. Sensitivity and weighted Cohen's weighted kappa (wκ) were calculated. An ordinal generalized linear mixed model identified factors influencing accurate DR staging. The study included 362 eyes from 189 patients. The LED camera excelled in identifying sight-threatening DR stages (sensitivity=0.83, specificity=0.95 for proliferative DR) and had the highest agreement with the GT (wκ=0.71). The addition of SWL to pseudocolor imaging resulted in decreased performance (sensitivity=0.33, specificity=0.98 for proliferative DR; wκ=0.55). Peripheral lesions reduced the likelihood of being staged in the same or higher DR category by 80% (P<0.001). Pseudocolor and LED cameras, although proficient, demonstrated non-interchangeable performance, with the LED camera exhibiting superior accuracy in identifying advanced DR stages. These findings underscore the importance of implementing AI systems trained for ultra-widefield imaging, considering the impact of peripheral lesions on correct DR staging. This study underscores the need for artificial intelligence-based systems specifically trained for ultra-widefield imaging in diabetic retinopathy assessment.

Proteomic analysis of diabetic retinopathy identifies potential plasma-protein biomarkers for diagnosis and prognosis.

To identify molecular pathways and prognostic- and diagnostic plasma-protein biomarkers for diabetic retinopathy at various stages. This exploratory, cross-sectional proteomics study involved plasma from 68 adults, including 15 healthy controls and 53 diabetes patients for various stages of diabetic retinopathy: non-diabetic retinopathy, non-proliferative diabetic retinopathy, proliferative diabetic retinopathy and diabetic macular edema. Plasma was incubated with peptide library beads and eluted proteins were tryptic digested, analyzed byliquid chromatography-tandem mass-spectrometry followed by bioinformatics. In the 68 samples, 248 of the 731 identified plasma-proteins were present in all samples. Analysis of variance showed differential expression of 58 proteins across the five disease subgroups. Protein-Protein Interaction network (STRING) showed enrichment of various pathways during the diabetic stages. In addition, stage-specific driver proteins were detected for early and advanced diabetic retinopathy. Hierarchical clustering showed distinct protein profiles according to disease severity and disease type. Molecular pathways in the cholesterol metabolism, complement system, and coagulation cascade were enriched in patients at various stages of diabetic retinopathy. The peroxisome proliferator-activated receptor signaling pathway and systemic lupus erythematosus pathways were enriched in early diabetic retinopathy. Stage-specific proteins for early- and advanced diabetic retinopathy as determined herein could be 'key' players in driving disease development and potential 'target' proteins for future therapies. For type 1 and 2 diabetes mellitus, the proteomic profiles were especially distinct during the early disease stage. Validation studies should aim to clarify the role of the detected molecular pathways, potential biomarkers, and potential 'target' proteins for future therapies in diabetic retinopathy.

Identification of Genetic Variants for Diabetic Retinopathy Risk Applying Exome Sequencing in Extreme Phenotypes.

Diabetic retinopathy (DR) risk has been shown to vary depending on ethnic backgrounds, and thus, it is worthy that underrepresented populations are analyzed for the potential identification of DR-associated genetic variants. We conducted a case-control study for the identification of DR-risk variants in Mexican population. We ascertained 60 type 2 diabetes mellitus (T2DM) patients. Cases (n = 30) were patients with advanced proliferative DR (PDR) with less than 15 years after a T2DM diagnosis while controls (n = 30) were patients with no DR 15 years after the diagnosis of T2DM. Exome sequencing was performed in all patients, and the frequency of rare variants was compared. In addition, the frequency of variants occurring in a set of 169 DR-associated genes were compared. Statistically significant differences were identified for rare missense and splice variants and for rare splice variants occurring more than once in either group. A strong statistical difference was observed when the number of rare missense variants with an aggregated prediction of pathogenicity and occurring more than once in either group was compared (p = 0.0035). Moreover, 8 variants identified more than once in either group, occurring in previously identified DR-associated genes were recognized. The p.Pro234Ser KIR2DS4 variant showed a strong protective effect (OR = 0.04 [0.001-0.36]; p = 0.04). Our study showed an enrichment of rare splice acceptor/donor variants in patients with PDR and identified a potential protective variant in KIR2DS4. Although statistical significance was not reached, our results support the replication of 8 previously identified DR-associated genes.

Vitreoretinal surgery in difficult cases

In the everyday practice, we are dealing with various level of difficulty, while performing vitreoretinal cases. There are some cases which require high level of skills and experience in order to perform successful and effective surgery. Refractory or myopic macular holes, optic disk pit cases, PVR cases, advanced proliferative diabetic retinopathy cases, trauma cases and paediatric vitreoretinal cases are some examples. The purpose of the SIS is a group of very experienced vitreoretinal surgeons with high volume of cases, to provide tips and pearls in to how to perform safer surgery, with the best results, anatomically and functionally. We will also provide advise into how to use chandelier additional lighting and how to use and remove heavy silicone oil and buckles.

Microaneurysm detection using high-speed megahertz optical coherence tomography angiography in advanced diabetic retinopathy.

To compare detection rates of microaneurysms (MAs) on high-speed megahertz optical coherence tomography angiography (MHz-OCTA), fluorescein angiography (FA) and colour fundus photography (CF) in patients with diabetic retinopathy (DR). For this exploratory cross-sectional study, MHz-OCTA data were acquired with a swept-source OCT prototype (A-scan rate: 1.7 MHz), and FA and CF imaging was performed using Optos® California. MA count was manually evaluated on en face MHz-OCTA/FA/CF images within an extended ETDRS grid. Detectability of MAs visible on FA images was evaluated on corresponding MHz-OCTA and CF images. MA distribution and leakage were correlated with detectability on OCTA and CF imaging. 47 eyes with severe DR (n = 12) and proliferative DR (n = 35) were included. MHz-OCTA and CF imaging detected on average 56% and 36% of MAs, respectively. MHz-OCTA detection rate was significantly higher than CF (p < 0.01). The combination of MHz-OCTA and CF leads to an increased detection rate of 70%. There was no statistically significant association between leakage and MA detectability on OCTA (p = 0.13). For CF, the odds of detecting leaking MAs were significantly lower than non-leaking MAs (p = 0.012). Using MHz-OCTA, detection of MAs outside the ETDRS grid was less likely than MAs located within the ETDRS grid (outer ring, p < 0.01; inner ring, p = 0.028). No statistically significant difference between rings was observed for CF measurements. More MAs were detected on MHz-OCTA than on CF imaging. Detection rate was lower for MAs located outside the macular region with MHz-OCTA and for leaking MAs with CF imaging. Combining both non-invasive modalities can improve MA detection.

Comparison of central corneal thickness and endothelial cell count among diabetic retinopathy and non-diabetic cases

: Diabetes is associated with alterations in the structure and functions of corneal endothelial cells. Current research has been carried out to compare the central corneal thickness and endothelial cell density in patients with diabetic retinopathy (DR) and non-diabetic (ND) individuals. : A Cross Sectional comparative research was carried out in a tertiary eye care hospital, over the period of two years from April 2021 to March 2023. Among 160 study participants, 80 cases with diabetic retinopathy (DR) and 80 non-diabetic (ND) cases as age matched control have been selected. Thorough Ophthalmic assessment was done. We have included only retinopathy cases as they have longer duration of diabetis and poorer metabolic control, for better comparison of the endothelium parameters with non-diabetics. Specular microscopy has been done in all cases for endothelial cell count evaluation and thickness of cornea has been estimated by Pachymeter. Statistical analysis was carried out by students‘t’ test by comparing the variables between two groups. : P-value was not significant for the mean age and sex distribution in the two groups. Mean endothelial cell density was lesser (2512.12±260.23cells/mm2) in DR than in ND group (2699.10±95.68cells/mm2). Mean central corneal thickness was greater (522.65±36.56μm) in DR than in ND group (486.50±18.67μm) (P&amp;#60;0.05). Also, the Co-efficient of variation percentage was more whereas the percentage of hexagonality was found to be statistically less in DR than ND group. Among DR patients, endothelial cell density was significantly reduced and central corneal thickness considerably raised when compared with ND. Our results also suggest that poor metabolic control and advanced Diabetic Retinopathy are risk factors for developing keratopathy.

Алгоритм лечения далеко зашедшей пролиферативной диабетической ретинопатии

Purpose. To develop an algorithm for the treatment of patients with advanced proliferative diabetic retinopathy with the determination of the stages of laser and surgical methods and evaluate its effectiveness. Material and methods. The study group included 38 patients (38 eyes) with type 1 diabetes mellitus (21 patients) and type 2 diabetes mellitus (17 patients, 16 of them with the insulin-requiring form of the disease). Patients age ranged from 24 to 75 years (41±8.6 years) old. All patients underwent staged treatment. Primary subtotal three-port 27 G vitrectomy was performed. Transpupillary patterned panretinal laser coagulation was performed at 1,5–2 months after the first stage of treatment. Panretinal laser coagulation was performed with a hexagonal matrix pattern with a laser spot diameter of 300 µm, exposure time of 30 ms on an Integre Pro Scan laser device (Ellex, Australia) with a wavelength of 561 nm using a panfundus lens. In cases of gas-air tamponade, panretinal laser coagulation was performed according to the same parameters in two sessions with an interval of 1–2 months between them, the average number of coagulates per session was 1053±107 applications. As the third stage of treatment, 1,5–2 months after panretinal laser coagulation, those patients whose vitreal cavity was tamponed with silicone oil underwent vitrectomy with the removal of silicone oil and it's replacement with a balanced solution. Results. The total number of treatment steps in the observation group (n=34) ranged from 1 to 5 and averaged 3±0.97. The time from primary vitrectomy followed by patterned panretinal laser coagulation to silicone oil removal was at average 3.7±0.48 months. Performing primary subtotal vitrectomy as the first stage of combined treatment made it possible achieve retinal attachment and its visualization throughout, to perform surgical intervention without massive endolaser coagulation, which reduced the duration of surgery and accelerated postoperative rehabilitation. The subsequent transpupillary panretinal laser coagulation of the retina in the pattern mode provided a dosed precision effect on the retina and made it possible perform the laser stage of treatment in one session. Conclusion. A step-by-step algorithm, including primary subtotal vitrectomy followed by simultaneous transpupillary pattern laser coagulation of the retina, is effective and safe in the treatment of proliferative diabetic retinopathy complicated by hemophthalmos. Key words: proliferative diabetic retinopathy, treatment algorithm, surgical treatment, laser treatment, vitrectomy, pattern laser coagulation

A STUDY TO ASSESS CHANGE IN CONTRAST SENSITIVITY AND VISUAL ACUITY IN PROLIFERATIVE DIABETIC RETINOPATHY PATIENTS UNDERGOING ANTI-VEGF TREATMENT AND ROLE OF LOW VISION AID IN SUCH PATIENTS

Objective: The aim of this study was to study the effect of intravitreal anti-vascular endothelial growth factor (VEGF) on the visual acuity (VA) using logMAR charts and the contrast sensitivity (CS) using the pelli-robson chart in patients of advanced diabetic retinopathy. Design: We performed a retrospective study to assess the change in CS and VA in diabetic retinopathy (DR) with or without proliferative DR patients receiving intra-vitreal anti VEGF. Methods: The study was done at our institution where 40 patients of DR were included in the study, 20 cases (20 eyes) and 20 controls (20 eyes). Moreover, it comes under the criteria of low vision and above 18 years of age and VA &gt;6/60. VA and CS were compared before injection and after injection at 14 days, 30 days, and 90 days, respectively. Results: On comparing the mean of CS change before injections and after injections at 14 days (p=0.036), 30 days (p=0.012), and 90 days (p=0.012), respectively, showed a significant association between change in CS change within group but on comparing with control group at 14 days (p=0.195), 30 days (p=0.247), 90 days (p=0.247), respectively, showed no significant association. Another comparison of mean VA before injection and after injection in the case group at 14 days, 30 days, and 90 days, respectively, (p=0.329) remains the same. Which is insignificant but on comparison with the control group (p=0.02) showed a significant association. Conclusion: Whatever VA and CS are achieved with anti-VEGF was completed at 14 days of injection.

Effectiveness of Silicone Oil Tamponade with Pars Plana Vitrectomy in Isolated Cases of Vitreous Hemorrhage with Advanced Diabetic Retinopathy

Purpose: To assess the effectiveness and safety of silicone oil as tamponade in vitrectomy performed for isolated cases of vitreous hemorrhage in patients with advanced diabetic retinopathy. Study Design: Quasi experimental. Place and Duration of Study: Al-Ibrahim Eye Hospital, Karachi from October 2022 to March 2023. Methods: Forty two cases of advanced diabetic retinopathy (either sex), with developing vitreous hemorrhage (active bleeding) were enrolled through convenient sampling. Demographic characteristics and pre-operative examination of eyes including Best corrected visual acuity (BCVA), intraocular pressure (IOP), indirect ophthalmoscopy, gonioscopy and ultrasonography (in cases where fundus was not visible) were performed. All the patients underwent pars plana vitrectomy (PPV) and pan retinal photocoagulation (PRP). Silicone oil was used as tamponade. Post-operative follow up was at first week after surgery and repeated at 3rd month and 6th month. Effect of silicon oil tamponade on re-bleeding after surgery was specifically observed. Anatomical outcome and side effects were also noted during the study period. Results: Out of 42 cases, re-bleed occurred in 2 cases (4.76 %). However, intraocular pressure (IOP) was raised in 3cases (7.1%) and cataract formed in 2 cases (4.76%). No other side effect was observed throughout the study period. Conclusion: Use of silicone oil as tamponade effectively decreases re-bleeding in patients of advanced diabetic retinopathy after vitrectomy. However, few complications such as increased intraocular pressure and cataract can occur that are manageable both medically and surgically.

Mean Platelet Volume in Type 2 Diabetes: Correlation with Poor Glycaemic Control

Background: Diabetes is a global pandemic. Mean platelet volume (MPV) is an indicator of increased platelet activity, which is considered to play a role in the development of vascular complications in diabetes. Platelet volume is strongly and independently related with glycaemic control in Type 2 diabetes (T2D). Aim: To study the MPV in patients with T2D, and its correlation with HbA1c, duration of T2D, and microvascular complications. Methodology: This was a cross-sectional, observational study conducted at the Department of Medicine, Gandhi Medical College, Bhopal, India, during a period of 18 months on 300 patients with T2D. Blood glucose, HbA1c, MPV, fundoscopy, and 24-hour urine protein were done. Data were represented as mean+/-standard deviation and statistical analysis was done using SPSS software (IBM, Armonk, New York, USA). Results: The mean age of patients was 56.64±8.69 years, with 52% of the patients being females. Of these patients, 18.3% had HbA1c between 6.5–8.0%, 51.7% between 8.1–10.0% and the rest above 10.0%. A total of 51% of the patients had diabetes for 6–10 years of duration and 30% for more than 10 years. Patients with higher HbA1c level and prolonged duration of diabetes had higher MPV (p&lt;0.001). Patients with advanced diabetic retinopathy changes and nephropathy also had higher MPV (p&lt;0.05). Conclusion: Measurement of MPV in patients with T2D can be a useful and easily available prognostic marker, and hence assist clinicians to anticipate the occurrence of microvascular complications associated with the disease, especially in resource-poor settings, and reduce the burden of cost for the patient.

Impact of Dyslipidemia Medications on the Prevalence of Diabetic Retinopathy Among a Large US Cohort

Background and Objective: Dyslipidemia medications such as statins and fibrates may be associated with a reduction in diabetic retinopathy (DR) progression, but real-world data is lacking. This study evaluates cholesterol-lowering medications and their association with the prevalence of DR and advanced DR complications. Patients and Methods: Data was collected using codes from the International Classification of Diseases on TriNetX, a cross-sectional database of over 79 million Americans, between June and August 2022. Prevalence and prevalence odds ratios (POR) were calculated. Results: Patients taking pitavastatin (OR 0.64, 95% CI 0.49, 0.84), fenofibrate (OR 0.83, CI 0.79, 0.87), or evolocumab (OR 0.80, CI 0.68, 0.95) had lower POR of proliferative DR compared to nonproliferative DR. Patients taking any cholesterol medication had a lower POR of vitreous hemorrhage. Patients taking fibrates also had lower POR of neovascular glaucoma. Conclusion: This exploratory study highlights positive associations between DR and dyslipidemia and medications that may have fewer worsening events in DR patients. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:626–633.]

Predictors of visual outcome after pars plana vitrectomy secondary to proliferative diabetic retinopathy.

Objective: Advanced proliferative diabetic retinopathy can lead to serious ophthalmological complications, including blindness. This research aimed to determine visual outcomes after pars plana vitrectomy secondary to proliferative diabetic retinopathy, as well as to identify its predictors. Methods: This prospective clinical study was performed in the Ophthalmology Clinic of the Clinical Centre University of Sarajevo. 60 subjects (eyes) with performed pars plana vitrectomy secondary to proliferative diabetic retinopathy were included in the study. Results: After univariate linear regression analysis, glucose, HbA1c, vascular endothelial growth factor, previous pan-retinal laser photocoagulation, baseline best corrected visual acuity, gas injection, vitreous haemorrhage, iris rubeosis, and glaucoma were found to be statistically significant parameters associated with postoperative visual outcome (p<0.05). Multivariate linear regression analysis was performed to evaluate the association between factors and postoperative best corrected visual acuity. Only intravitreal vascular endothelial growth factor concentration, previous pan-retinal photocoagulation, and gas injection remained statistically significant associated with postoperative best corrected visual acuity (p<0.05). Conclusion: Vitrectomy is an effective treatment for advanced proliferative diabetic retinopathy. Factors correlated with the better visual outcome are good systemic control, previous pan-retinal photocoagulation, low intravitreal vascular endothelial growth factor concentration, younger age, intraoperative internal gas tamponade, combined phacoemulsification and pars plana vitrectomy surgery, and the absence of postoperative complications. Abbreviations: PDR = proliferative diabetic retinopathy, VEGF = vascular endothelial growth factor, TDR = tractional retinal detachment, BCVA = best corrected visual acuity, DR = diabetic retinopathy, RDD = rhegmatogenous retinal detachment, NVG = neovascular glaucoma, BRVO = branch retinal vein occlusion, CBC = complete blood count, DBT = differential blood count, ESR = erythrocyte sedimentation rate, HbA1c = glycosylated hemoglobin, PHACO = phacoemulsification, ILM = internal limiting membrane, PPV = pars plana vitrectomy, IOP = intraocular pressure, PRP = pan-retinal photocoagulation, ETDRS = Early treatment diabetic retinopathy study.

Association between macrophage-like cell density and ischemia metrics in diabetic eyes

We previously showed that macrophage-like cells (MLCs) are increased in eyes with advanced diabetic retinopathy (DR). Here, we hypothesized that MLC density was correlated with ischemia using optical coherence tomography angiography (OCTA) and ultra-widefield fluorescein angiography (UWF-FA). Treatment-naïve diabetic eyes were prospectively imaged with repeated OCTA (average 5.3 scans per eye) and UWF-FA imaging. OCTA images were registered and averaged to generate a superficial capillary plexus (SCP), deep capillary plexus (DCP), and MLC slab. We calculated geometric perfusion deficit (GPD), vessel length density, and vessel density for the SCP and DCP. MLC density was quantified by two masked graders and averaged. Ischemia on UWF-FA was measured to generate a non-perfusion area (NPA) and index (NPI). Since MLC density was non-parametrically distributed, MLC density was correlated with ischemia metrics using Spearman correlations. Forty-five treatment-naïve eyes of 45 patients (59 ± 12 years of age; 56% female) were imaged. We included 6 eyes with no DR, 7 eyes with mild non-proliferative DR (NPDR), 22 moderate NPDR, 4 severe NPDR, and 6 PDR eyes. MLC density between graders was highly correlated (r = 0.9592, p < 0.0001). MLC density was correlated with DCP GPD (r = 0.296, p = 0.049), but no other OCTA ischemia metrics. MLC density was also correlated with UWF-FA NPA (r = 0.330, p = 0.035) and NPI (r = 0.332, p = 0.034). MLC density was correlated with total ischemia on UWF-FA and local DCP GPD. Since both UWF-FA and DCP non-perfusion are associated with higher risk for DR progression, MLC density could be another potential biomarker for DR progression.

Association of inflammation-related markers and diabetic retinopathy severity in the aqueous humor, but not serum of type 2 diabetic patients.

Diabetic retinopathy (DR) is a frequent microvascular complication of diabetes mellitus, and inflammatory pathways have been linked to its pathogenesis. In this retrospective, observational pilot study, we aimed to compare the concentrations of four inflammation-related proteins, ZAG, Reg-3a, elafin and RBP-4, in the serum and aqueous humor of healthy controls and diabetic patients with different stages of DR. The concentrations of VEGF-A, IL-8, IL-6 were determined in parallel as internal controls. In the serum, we did not find significant differences in the concentrations of target proteins. In the aqueous humor, higher levels of ZAG, RBP-4, Reg-3a and elafin were observed in advanced nonproliferative DR (NPDR)/ proliferative DR (PDR) compared to controls. The levels of ZAG and RBP-4 were also higher in advanced NPDR/PDR than in nonapparent DR. Normalization of target protein concentrations to the aqueous humor total protein demonstrates that a spill-over from serum due to breakage of the blood-retina barrier only partially accounts for increased inflammation related markers in later stages. In conclusion, we found elevated levels of Reg-3a, RBP-4, elafin and ZAG in advanced stages of diabetic retinopathy. Higher levels of pro-inflammatory proteins, Reg-3a and RBP-4, might contribute to the pathogenesis of diabetic retinopathy, as the parallel increased concentrations of anti-inflammatory molecules elafin and ZAG might indicate a compensatory mechanism.

Risk of Diabetic Retinopathy in Patients With Type 2 Diabetes After SGLT-2 Inhibitors: A Nationwide Population Cohort Study.

Diabetic retinopathy (DR) accounts for 80% of cases of vision loss in patients with type 2 diabetes mellitus (T2DM). Interventional treatments are only indicated in advanced DR and are ineffective in some patients. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are used to attenuate T2DM-associated cardiovascular complications. We conducted the cohort study to investigate the effect of SGLT2is on DR development. Data (May 2016-December 2018) obtained from the Taiwan National Health Insurance Research Database were analyzed in this nationwide retrospective cohort study. After propensity score matching, a total of 31,764 patients receiving SGLT2is and another 31,764 patients receiving dipeptidyl peptidase 4 inhibitors (DPP4is) were included in this study. Multiple Cox proportional-hazards regression models were used to evaluate DR risk. Overall DR incidence among SGLT2i or DPP4i users was 10.9 or 15.6 per 10,000 patient-years, respectively. After covariate adjustment, DR (both early and late stage) risk was substantially lower in SGLT2i users (adjusted hazard ratio: 0.68, 95% confidence interval: 0.6-0.78) than in DPP4i users. DR risk appears to be considerably lower in SGLT2i users than in DPP4i users. Glycemic control measurement with HbA1C level was unavailable in this claim database.

Rates of diabetic retinopathy among cluster analysis—identified type 2 diabetic mellitus subgroups

PurposeTo determine whether phenotypic clustering of patients with diabetes mellitus (DM) is associated with more advanced diabetic retinopathy (DR).MethodsRetrospective cohort study of 495 patients with no prior DR treatment seen at a tertiary care clinic 2014–2020. Four previously identified clusters from Ahlqvist’s 2018 paper were reproduced utilizing baseline hemoglobin A1c, body mass index, and age at DM diagnosis. Age-adjusted Cox proportional hazard ratios were used to compare clusters with reference as the lowest risk cluster.ResultsAll four type 2 DM clusters were replicated with our cohort. There was a significant difference in racial distribution among clusters (p = 0.018) with severe insulin-resistant diabetes (SIRD) having the higher percentage of Caucasians and lower percentage of Hispanics compared to other groups and a higher percentage of African Americans comprising the severe insulin-deficient diabetes (SIDD) cluster than other groups. Rates of proliferative diabetic retinopathy were higher in mild obesity-related diabetes (MOD) (28%), SIDD (24%), mild age-related diabetes (MARD) (20%), and lowest in SIRD (7.9%), overall p = 0.004. Rates of vitreous hemorrhage were higher in MOD (p = 0.032) and MARD (0.005) compared to SIRD.ConclusionBaseline clinical measures may be useful in risk stratifying patients for progression to retinopathy requiring intervention.