Stages Of Diabetic Macular Edema Research Articles

ASSOCIATION OF DIABETIC MACULAR EDEMA WITH QUALITY OF LIFE IN PATIENTS WITH TYPE 2 DIABETES: The Fushun Diabetic Retinopathy Cohort Study.

To report the vision-related quality of life in patients with diabetic macular edema (DME) in a population-based study. In this cross-sectional study, we analyzed 1,659 subjects with type 2 diabetes. Questionnaires were administered to assess the patient's vision-related quality of life. Diabetic macular edema severity was graded according to the established protocols. A subject's DME score ranged from 1 (no DME in either eye) to 7 (severe bilateral DME) using predefined criteria. Composite 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores for participants with DME were 88.9 (interquartile range [IQR]: 76.2-94.9) compared with 92.0 (IQR: 82.7-96.0) for those without DME ( P < 0.001). Locally weighted scatterplot smoothing plots depicted a consistent decline in composite NEI-VFQ-25 scores corresponding to the escalation of bilateral DME severity: starting from 88.59 for no DME in either eye, progressing through 86.65, 85.83, 85.31, 84.91, 83.85, and culminating at 82.71 for bilateral severe DME. Notably, the locally weighted scatterplot smoothing plots highlighted significant NEI-VFQ-25 composite score reduction at unilateral mild DME (slope m = -1.94). Significant changes in vision-related quality of life manifest in the early stage of DME. Therefore, early identification and intervention for these patients are crucial clinical objectives.

Optical Coherence Tomography-Based Grading of Diabetic Macular Edema Is Associated with Systemic Inflammatory Indices and Imaging Biomarkers

Introduction: Objectives of the study were to investigate the correlation between optical coherence tomography (OCT)-based grading of diabetic macular edema (DME) and systemic inflammatory indices, imaging biomarkers, and early anti-vascular endothelial growth factor (VEGF) treatment response. Methods: A total of 111 eyes from 111 patients with DME treated with intravitreous anti-VEGF therapy for 3 consecutive months every month were enrolled in this retrospective study. According to a protocol termed “TCED,” DME was divided into early, advanced, severe, and atrophic stages. The best-corrected visual acuity (BCVA), subretinal fluid (SRF), and the number of hyperreflective foci (HRF) in the whole retinal layers were analyzed at baseline and 3 months after the first injection. Peripheral blood inflammatory indices were calculated, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet (PLT)-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and C-reactive protein (CRP). Statistical analysis was performed to compare the visual and anatomical results and evaluate HRF and SRF in different stages of DME before and after treatment. Results: There were significant differences in systemic inflammatory indices among the four groups, including NLR, PLR, MLR, SII, and CRP (all p < 0.05). The CRP, NLR, PLR, MLR, and SII were significantly higher in the atrophic stage compared to the advanced stage (all p < 0.05). Conversely, the CRP, NLR, PLR, MLR, and SII were significantly lower in the advanced stage compared to the early stage (all p < 0.05). Except for the atrophic stage, BCVA and central retinal thickness (CRT) were significantly improved after treatment in early, advanced and severe stages (all p < 0.05), especially in the severe stage. The decline in the proportion of SRF and HRF ≥20 was the most significant in the advanced stage after anti-VEGF treatment (p < 0.001, p = 0.016), but not in the early and severe stages (all p > 0.05). Conclusion: Systemic inflammatory indices and the decline in the proportion of SRF and HRF ≥20 were closely associated with different stages of DME based on “TCED.” Meanwhile, the “TCED” grading system can predict visual and anatomical prognosis of DME after anti-VEGF treatment, which may be a biomarker for identifying risk stratification and management of DME.

OCT biomarkers as predictors of visual improvement in diabetic macular edema eyes receiving dexamethasone implants

BackgroundSeveral optical coherence tomography (OCT) biomarkers have been proposed as predictors for functional and anatomical outcomes in Diabetic Macular Edema (DME). This study aims to examine the impact of these OCT features on the visual acuity improvement of patients with DME after long-acting Dexamethasone intravitreal implants (DEX-I) injection. Furthermore, the safety and impact of DEX-I on clinical parameters, including intraocular pressure (IOP) were assessed.MethodsIn this retrospective observational study, we reviewed the medical records of naïve and non-naïve eyes with DME who received at least one DEX-I. The primary endpoint was visual acuity improvement of ≥ 5 ETDRS letters at 1 month and 4 months after treatment. Secondary outcomes were the changes in OCT biomarkers and the impact of DEX-I on IOP at 1 and 4 months of follow-up. Linear panel regression analysis was used to test for differences in central subfield thickness (CST) over time and it was stratified according to biomarkers at baseline. Finally, a logistic regression analysis was used to identify factors predicting visual improvement at 1 and 4 months.ResultsWe included 33 eyes of which 63.6% were at an advanced stage of DME. Overall, CST, cube average thickness (CAT), cube volume (CV), and intraretinal cystoid spaces > 200 μm (ICS) decreased following DEX-I injection (p < 0.001). Additionally, a thicker CST at baseline was observed in eyes with better visual improvement at one month (p = 0.048). After logistic regression analysis, CST was retained as the only predictor for visual improvement at one month (p = 0.044). Furthermore, panel regression analysis identified a relation between subfoveal neuroretinal detachment (SND) at baseline and CST increase at four months. Lastly, only 15.2% of the eyes necessitated topical medication for IOP reduction, with no differences observed when stratifying between naïve and non-naïve eyes.ConclusionOur analyses suggest that a ticker baseline CST may serve as a positive predictor of early visual improvement and SND presence at baseline may be a negative prognostic factor for CST increase 4 months after DEX-I injection. Other well-known biomarkers, such as disorganization of the inner retinal layers (DRIL) and hyperreflective foci (HF), did not demonstrate prognostic value on visual outcomes, at least within the first four months following the injection.

Optical coherence tomography angiography metrics in different stages of diabetic macular edema

BackgroundTo investigate the optical coherence tomography angiography (OCTA) characteristics of diabetic macular edema (DME) at different stages.MethodsThis study was a cross-sectional study. Patients diagnosed with DME were recruited. DME was classified into early, advanced, and severe DME. The vessel density (VD) in the superficial vascular plexus (SVP), deep vascular plexus (DVP) and foveal avascular zone (FAZ) parameters, including FAZ area, FAZ perimeter, acircularity index and foveal VD in a 300-μm-wide region around the FAZ (FD-300), were calculated by the AngioVue software. A multivariate generalized estimating equation was used to evaluate the associations between visual acuity and OCTA metrics.ResultsNinety-two eyes from 74 patients with DME were included in this study. Compared to early (P = 0.006) and advanced DME (P = 0.003), the acircularity index was higher in severe DME. Both whole and parafoveal VD in the DVP decreased in eyes with severe DME compared to early DME (P = 0.018, P = 0.005, respectively) and advanced DME (P = 0.035, P = 0.012, respectively). In the multivariate generalized estimating equation, DME severity, FAZ area and foveal thickness were positively associated with worse visual acuity (P = 0.001, P = 0.007 and P = 0.001, respectively).ConclusionCompared to early and advanced DME, severe DME showed increased irregularity in the FAZ and more extensive vessel damage in the DVP. Greater severity level of DME, larger FAZ area, and increased foveal thickness could be risk factors for poor visual acuity.Trial registration The protocol was published in the Chinese Clinical Trial Registry (ChiCTR2000033082).

Differential response to intravitreal dexamethasone implant in na\xefve and previously treated diabetic macular edema eyes

BackgroundTo identify different response patterns to intravitreal dexamethasone implants (IDI) in naïve and previously treated (PT) diabetic macular edema (DME) eyes in a real-life setting.Methods342 IDI injections (203 DME eyes) were included. Number of IDI injections, percentage (%) of eyes with 1, 2, 3 and ≥ 4 injections, time to reinjections, visual acuity (VA), intraocular pressure (IOP) and central retinal thickness (CRT) were evaluated for naïve and PT DME eyes over 24 months.ResultsMean number of injections was significantly lower in naïve vs PT DME eyes (1.40 ± 0.9 vs 1.82 ± 0.9, p < 0.001). The percentage of eyes receiving 1 injection was significantly higher in naïve vs PT DME eyes (76.1 vs 47.7), (p < 0.001). However, it was significantly lower for 2 (16.4 vs 29.4), or 3 injections (1.4 vs 17.6) (both p < 0.001), with no differences in eyes receiving ≥4 injections (5.9 vs 5.1 respectively, p = 0.80). Mean time to reinjection was not significantly different between both groups for the second, third and fourth injection (9.6 ± 4.0 vs 10.0 ± 5.5, p = 0.75, 13.2 ± 4.0 vs 16.0 ± 3.5, p = 0.21 and 21.7 ± 3.8 vs 19.7 ± 5.8, p = 0.55). VA scores were consistently better in naïve vs PT DME eyes at all studied timepoints, with no significant differences in CRT reduction or adverse effect rates.ConclusionNaïve DME eyes received lower number of IDI injections and showed better VA levels than PT DME eyes for 24 months in a real-world setting. This data supports the IDI use in early DME stages and provide further evidence of better IDI response when used as first-line therapy.

Spectral domain optical coherence tomography classification of diabetic macular edema: a new proposal to clinical practice.

To classify the types of diabetic macular edema (DME) and evaluate its morphological features on spectral domain optical coherence tomography (SD-OCT) and determine correlations between visual acuity and OCT findings. We assessed 406 eyes of 309 patients with a diagnosis of DME retrospectively. Three types based on SD-OCT were identified: diffuse macular edema, cystoid macular edema, and cystoid degeneration. Morphological features such as serous macular detachment (SMD), vitreomacular interface abnormalities (VMAI), hard exudates, photoreceptor status, and correlations between visual acuity and those morphological features were also evaluated by SD-OCT. The most common type of DME was cystoid edema (68.5%). No statistically significant difference was found between groups in sex (P = 0.40), type of diabetes (P = 0.50), or diabetic retinopathy (P=0.78). However, the duration of symptoms and BCVA was significantly lower in the group with cystoid degeneration compared with the group with cystoid edema (P < 0.001) and the group with diffuse macular edema (P < 0.001). In the group with cystoid degeneration compared with the groups with cystoid and diffuse edema, the central fovea and central subfield were significantly thicker (both (P < 0.001), the subfoveal choroid was significantly thinner (P = 0.049), rate of serous macular detachment was significantly lower (P < 0.001), and the rate of outer retinal damage was significantly higher (P < 0.001). Cystoid macular degeneration, which is consistent with poor functional and morphological outcomes, should be differentiated from cystoid macular edema. Serous macular detachment, which is mostly seen in eyes with early stages of DME, should be evaluated as an accompanying morphological finding rather than a type of DME.

Оцінювання діабетичного макулярного набряку за допомогою апарату нечітких множин

The paper proposes a mathematical model based on the description of cause and effect relationships between risk factors and a specific diagnosis, which are presented in the form of expressions that are convenient for formalization with the help of fuzzy logic, which allows for comprehensive diagnosis of the retina and macular diagnosis. The criteria for the classification of stages of diabetic macular edema, which allow to combine the main features of the disease, taking into account the anatomical and functional results of modern methods of diagnosis, have been formed.

RETINAL HYPERREFLECTIVE FOCI IN TYPE 1 DIABETES MELLITUS.

To investigate hyperreflective foci (HF) on spectral-domain optical coherence tomography in patients with Type 1 diabetes mellitus across different stages of diabetic retinopathy (DR) and diabetic macular edema (DME) and to study clinical and morphological characteristics associated with HF. Spectral-domain optical coherence tomography scans and color fundus photographs were obtained of 260 patients. Spectral-domain optical coherence tomography scans were graded for the number of HF and other morphological characteristics. The distribution of HF across different stages of DR and DME severity were studied. Linear mixed-model analysis was used to study associations between the number of HF and clinical and morphological parameters. Higher numbers of HF were found in patients with either stage of DME versus patients without DME (P < 0.001). A trend was observed between increasing numbers of HF and DR severity, although significance was only reached for moderate nonproliferative DR (P = 0.001) and proliferative DR (P = 0.019). Higher numbers of HF were associated with longer diabetes duration (P = 0.029), lower high-density lipoprotein cholesterol (P = 0.005), and the presence of microalbuminuria (P = 0.005). In addition, HF were associated with morphological characteristics on spectral-domain optical coherence tomography, including central retinal thickness (P = 0.004), cysts (P < 0.001), subretinal fluid (P = 0.001), and disruption of the external limiting membrane (P = 0.018). The number of HF was associated with different stages of DR and DME severity. The associations between HF and clinical and morphological characteristics can be of use in further studies evaluating the role of HF as a biomarker for disease progression and treatment response.

Modeling a Telemedicine Screening Program for Diabetic Retinopathy in Iran and Implementing a Pilot Project in Tehran Suburb.

Purpose To model a community-based telescreening program for diabetic retinopathy (DR) in Iran and to implement a pilot project at the Iranian Diabetes Society (IDS) branch in a Tehran suburb. Methods In this mixed model study, a web application called the “Iranian Retinopathy Teleophthalmology Screening (IRTOS)” was launched. The educational course for DR screening was established for general practitioners (GPs). Registered patients in IDS branch were recalled for fundus photography; images were transferred to the reading center via IRTOS to be graded by GPs, and patients were informed about the results via mobile messaging. All images were independently reviewed by a retina specialist as the gold standard. Patients who required further assessment were referred to an eye hospital. Results Overall, 604 subjects with diabetes were screened; of these, 50% required referral. The sensitivity and specificity for diagnosis of any stage of DR by trained GPs were 82.8% and 86.2%, respectively, in comparison to the gold standard. The corresponding values for detecting any stage of diabetic macular edema (DME) were 63.5% and 96.6%, respectively. Conclusions Telescreening was an effective method for detecting DR in a Tehran suburb. This screening model demonstrated its capacity for promoting diabetic eye care services at the national level. However, the sensitivity for detecting DME needs to be improved by modifying the referral pathway and promoting the skill of GPs.

Characterization of Initial Stages of Diabetic Macular Edema

Purpose: This study is aimed at characterizing the type of retinal edema in the initial stages of retinopathy in type 2 diabetes. Methods: In this retrospective cross-sectional study, spectral domain optical coherence tomography (OCT) layer by layer analysis of the retina in association with OCT-Leakage, an algorithm to detect sites of low optical reflectivity, were used to examine eyes with minimal, mild, and moderate diabetic retinopathy (DR). Results: A total of 142 eyes from 142 patients (28% women) aged 52–88 years were imaged. Macular edema, either subclinical (SCME) or central-involved macular edema (CIME), was present in 43% of eyes in group 10–20, 41% of eyes in group 35, and 38% of eyes in group 43–47. The inner nuclear layer (INL) was the layer showing higher and most frequent increases in retinal thickness (79%). The edema was predominantly intracellular in group 10–20 (65%) and extracellular in groups 35 (77%) and 43–47 (69%). Conclusions: Eyes from diabetic patients in the initial stages of DR with different Early Treatment Diabetic Retinopathy Study gradings show similar prevalence of SCME and CIME, independent of the severity of the retinopathy. Retinal edema is located mainly in the INL and appears to be mostly extracellular except in the earliest stages of diabetic retinal disease where intracellular edema predominates.

Choroidal thickness in type 2 diabetic patients with various stages of diabetic macular edema and retinopathy: A prospective study from central India

Background: The objective of this study is to assess the changes in choroidal thickness in patients with type 2 diabetes with diabetic macular edema (DME) and diabetic retinopathy (DR), using enhanced-depth imaging (EDI) spectral domain optical coherence tomography (OCT). Materials and Methods: A total of 164 eyes from 104 patients were divided into no DR, DR without DME, and DR with DME. Eyes were also divided according to subtypes of DME. Subfoveal choroidal thickness (SFChT) and parafoveal choroidal thickness (PFChT) at 500 μm, 1000 μm and 1500 μm were measured using EDI-OCT and compared across groups. Results: A sample of 104 patients with diabetes consisted of 28 females and 76 males. The adjusted mean SFChT was 266.1 ± 42.40 μm in no DR eyes, 258.32 ± 39.52 μm in DR without DME eyes, and 246.11 ± 35.42 μm in DR with DME eyes (P = 0.028). The adjusted mean SFChT was 242.5 ± 33.04 μm in spongy edema eyes, 242.05 ± 39.73 μm in cystic edema eyes, and 247.9 ± 39.54 μm in serous retinal detachment eyes (P

Central retinal thickness assessment in a real life setting after cataract surgery in diabetic patients

To assess in a real life setting the progression of central retinal thickness (CRT) during the first month after surgery in diabetic patients without previous diabetic macular edema (DME) and to identify potential risk factors for DME leading to increased postoperative follow-up. We conducted a prospective study of diabetic patients without history of DME who underwent uncomplicated cataract surgery. Best-corrected visual acuity (BCVA) and SD-OCT were performed 7 days and 1 month after surgery. We assumed absence of preoperative DME when there was no edema of SD-OCT at D7. Our primary endpoint was the central retinal thickness (CRT) variation between 7 days and 1 month after cataract surgery in patients without previous history of DME. We included 55 eyes of 42 patients. BCVA was 0.57±0.72 logMar (20/80) prior to surgery and increased significantly to 0.11±0.17 (20/25) at one month (P=0.001) post-surgery. The mean baseline CRT was 209±35μm and 229±69μm (P=0.06) one month after surgery. Four eyes (7.4%) developed macular edema at one month. We found no linear correlation between HbA1C and CRT. We found no link between a high level of HbA1C and postoperative increase in CRT. We found that cataract surgery in diabetic patients without previous DME has no negative impact on CRT, and visual outcomes are good. We suggest that in diabetic patients without complete visual recovery at 1-month post-cataract surgery, OCT examination should be performed in order to detect an early stage of DME.

Outcomes of pars plana vitrectomy for the treatment of persistent diffuse diabetic macular edema

Aim The aim of this study was to evaluate surgical outcome of pars plana vitrectomy on patients with persistent diffuse diabetic macular edema (dDME) in the presence or absence of complete posterior vitreous detachment (PVD). Patients and methods Pars plana vitrectomy was performed on 37 eyes of 37 patients with dDME. They were divided into two groups: group I consisted of 21 eyes of 21 patients with dDME and attached posterior vitreous face. Group II consisted of 16 eyes of 16 patients with dDME and detached posterior vitreous face. Both visual acuity (VA) as logMAR values and central macular thickness using optical coherence tomography were measured before,1, 3, and 6 months postvitrectomy. Results The baseline VA was 0.8±0.17 and 0.7±0.39 logMAR in groups I and II, respectively. One month after vitrectomy, VA significantly improved to 0.5±0.23 (P=0.002) and to 0.5±0.24 (P=0.015) in groups I and II, respectively. The VA was 0.4±0.13 (P=0.001), 0.5±0.19 (P=0.003) 3 months postvitrectomy and was 0.4±0.25 (P=0.005) and 0.5± 0.22 (P=0.014) after 6 months in groups I and II, respectively. The mean foveal thickness before surgery was 598.6±105.4 and 520.87±103.15 µm in groups I and II, respectively. After 3 months it significantly improved to 235.25±110.2 µm (P=0.0001) and 280.23±112.3 µm (P=0.002), whereas after 6 months it was 220.13±98.15 and 270.62±85.15 µm in groups I and II, respectively. Conclusion Vitrectomy with removal of the posterior hyaloid face and the premacular vitreous pocket may achieve resolution of dDME and improve vision in some patients who failed to respond to conventional treatment. The visual and anatomical outcomes seem to be better in eyes with early stages of diabetic macular edema and good preoperative VA.

Subthreshold micropulse laser reduces anti-VEGF injection burden in patients with diabetic macular edema

To evaluate the efficacy of micropulse laser in the early treatment of diabetic macular edema (DME) and its associated burden of anti-vascular endothelial growth factor (VEGF) injections. This retrospective comparative study compared a group of 19 eyes with DME treated with micropulse laser to a matched control group of 19 eyes with DME treated with ranibizumab injections without micropulse laser. Recorded parameters included previous medical and ocular history, previous and subsequent ranibizumab injections administered for DME, visual acuity (VA), central macular thickness throughout the follow-up period, and the occurrence of any complications. The improvement in VA was comparable in both groups, at 12 months and at the final follow-up. Patients treated with micropulse laser required significantly fewer ranibizumab injections than their controls, both at 12 months (1.7 ± 2.3 vs 5.6 ± 2.1) and by the end of the follow-up (2.6 ± 3.3 vs 9.3 ± 5.1) (p<0.001 for both). No complications related to the micropulse laser were encountered. Micropulse laser is a safe and effective treatment for DME, which may achieve comparable improvement in VA along with a significant reduction in the burden of anti-VEGF injections. We suggest a treatment approach for its inclusion in the early stages of DME.

Correlation between diabetic retinopathy severity and elevated skin autofluorescence as a marker of advanced glycation end-product accumulation in type 2 diabetic patients

AimsWe evaluated skin autofluorescence (AF) as a marker of tissue advanced glycation end-product (AGE) accumulation and examined whether it was related to the prevalence and severity of diabetic retinopathy (DR) and of diabetic macular edema (DME) in patients with type 2 diabetes mellitus (DM). MethodsThis study included 138 type 2 DM patients consisting of 31 patients with proliferative DR, 71 patients with non-proliferative DR, and 36 patients without retinopathy, in addition to 111 non-DM control subjects. At the time of skin AF and HbA1c measurement, self-assessed duration of DM was also determined. DR and DME stages were classified according to international guidelines. ResultsSkin AF was significantly increased in patients with DM as compared with non-DM controls. Furthermore, skin AF was correlated with the severity of DR, whereas single measurement of HbA1c and self-assessed DM duration were not. None of these 3 factors showed a correlation with DME prevalence or severity. ConclusionsSkin AF levels, which can be measured non-invasively on a screening basis without skin biopsy or blood sampling, have a greater predictive ability for the presence and severity of DR than single measurement of HbA1c or self-assessed DM duration in patients with type 2 DM.

Functional and morphological changes in diabetic macular edema over the course of anti-vascular endothelial growth factor treatment

To evaluate macular morphology and function in diabetic macular edema (DME) over the course of intravitreal anti-vascular endothelial growth factor (VEGF) treatment with Ranibizumab. A consecutive series of 39 study eyes with centre-involving DME were included in this study. In all subjects, best-corrected visual acuity (BCVA) according ETDRS protocol, fluorescein angiography (FA), microperimetric macular sensitivity (MP) and Spectral Domain optical coherence tomography (SD-OCT) cross-sectional scans were obtained before treatment and after 3 monthly applied intravitreal Ranibizumab injections. Six different morphological qualities [IS/OS layer integrity, outer nuclear layer (ONL) cysts, ONL cyst size, inner nuclear layer (INL) cysts, blocking phenomenon and subretinal fluid] were graded of each cross-sectional OCT scan before and over the course of treatment by two experienced graders. Correlation analyses between functional and morphological parameters were obtained. Mean BCVA increased from 26 ± 14 to 33 ± 13 letters after 3 consecutive monthly applied Ranibizumab injections (p < 0.001). Central retinal thickness (CRT) decreased from 504 ± 144 to 387 ± 122 μm (p < 0.001). Over the course of treatment, IS/OS continuity improved (index: 0.56 ± 0.52 to 0.43 ± 0.49, Z = -1.415, p = 0.157), ONL cyst prevalence and size decreased significantly (index: 0.61 ± 0.44 to 0.56 ± 0.35, Z = -3.41, p = 0.001 and 1.75 ± 0.88 to 1.17 ± 1.05, Z = -4.02, p < 0.001), INL cyst prevalence decreased (index: 0.35 ± 0.52 to 0.28 ± 0.52, Z = -1.60, p = 0.109), blocking phenomenon did not change significantly (index: 00.12 ± 0.16 to 0.13 ± 0.15, Z = -0.45, p = 0.656) and subretinal fluid almost disappeared (index: 0.10 ± 0.24 vs. 0.00 ± 0.01, Z = -2.56, p = 0.011). Correlation analyses revealed highest significant correlations between ONL cyst prevalence and their size and CRT as well as BCVA and MP before treatment and over the course of treatment. ONL cysts and their size as morphological parameters correlate with retinal function measured with BCVA and microperimetry before and over the course of anti-VEGF therapy with Ranibizumab in patients with DME.

LONG-TERM EFFECT OF INTRAVITREAL BEVACIZUMAB (AVASTIN) IN PATIENTS WITH CHRONIC DIFFUSE DIABETIC MACULAR EDEMA

To evaluate the long-term efficacy of bevacizumab for the treatment of chronic diffuse diabetic macular edema after various previous treatments. A total of 126 patients (mean age: 66 years) with chronic diffuse diabetic macular edema were consecutively incorporated in this prospective, noncomparative case series. Inclusion was performed independently from the size of edema, retinal thickness, visual acuity (VA), age, metabolic control, type of diabetes, or type of previous treatments. The patients underwent a complete eye examination including best-corrected VA with ETDRS charts, slit lamp examination, intraocular pressure measurement, stereoscopic biomicroscopy of the macula, retinal thickness measurement using optical coherence tomography (OCT), fluorescein angiography, and fundus photography. All patients were treated with repeated intravitreal injections of bevacizumab (1.25 mg). Patients were observed in intervals of 4-12 weeks for a period of up to 6-12 months. All patients had received various previous treatments such as laser treatment (62% focal laser treatment, 38% panretinal laser treatment), vitrectomy (11%), or intravitreal injection of triamcinolone (41%). All patients completed 6 months and 59 patients (47%) completed 12 months of follow-up; within this period 48% had received at least three intravitreal injections of bevacizumab. Mean diameter of foveal avascular zone was 858 +/- 341 microm. At baseline mean VA was 40.3 ETDRS letters (0.82 logMAR Snellen VA) and mean central retinal thickness on OCT was 463 microm. Throughout follow-up VA changes were not significant with a mean change of -1.6 ETDRS letters after 6 months, but significant with +5.1 ETDRS letters after 12 months. Mean central retinal thickness (OCT) decreased to 374 microm after 6 months (P < 0.001) and to 357 microm after 12 months (P < 0.001). Changes of retinal thickness and visual acuity did not correlate. No other factors investigated, such as age, central retinal thickness, or previous treatments, were predictive for a change of VA. Macular ischemia was not exacerbated as a result of the treatment. Even in cases with chronic diffuse ischemic diabetic macular edema, a long-term decrease of central retinal thickness can be observed following repeated intravitreal injections of bevacizumab. In these patients, mean decrease in retinal thickness is aligned with a gain in mean VA. Treatment with bevacizumab at an earlier stage of diabetic macular edema without ischemia may be associated with an even better functional outcome.

Intravitreal steroids for macular edema in diabetes

Macular edema is secondary to leakage from diseased retinal capillaries and is an important cause of poor central visual acuity in patients with diabetic retinopathy. This review evaluated the effectiveness and safety of intraocular steroids in treating diabetic macular edema (DME). We searched CENTRAL, MEDLINE, EMBASE in June 2007, reference lists, Science Citation Index and conference proceedings. We included randomized clinical trials (RCTs) evaluating any form of intravitreal steroids for treating DME. Two authors independently assessed eligibility, methodological quality and extracted data. We performed meta-analyses when appropriate. Seven studies, involving 632 DME eyes were included. Four examined the effectiveness of intravitreal triamcinolone acetate injection (IVTA), three examined intravitreal steroids implantation (fluocinolone acetonide implant (FAI) or dexamethasone drug delivery system (DDS)). Two trials were at low risk of bias, one was at median risk of bias, two were at high risk of bias and the remaining two were at unclear risk of bias. The preponderance of data suggest a beneficial effect from IVTA. Comparing IVTA with controls, the mean difference in visual acuity was -0.15 LogMAR (95% CI -0.21 to -0.09) at 3 months (based on three trials), -0.23 LogMAR (95% CI -0.33 to -0.13) at 6 months (two trials), -0.29 LogMAR (95% CI -0.47 to -0.11) at 9 months (one trial), and -0.11 LogMAR (95% CI -0.20 to -0.03) at 24 months (one trial), all in favor of IVTA. The relative risk (RR) for one or more lines improvement in visual acuity was 2.85 (95% CI 1.59 to 5.10) at 3 months (two trials), 1.25 (95% CI 0.66 to 2.38) at 6 months (one trial), and 2.17 (95% CI 1.15 to 4.11) at 24 months (one trial), all in favor of IVTA. We did not find evidence for three or more lines improvement in visual acuity. The mean difference in retinal thickness was -131.97 um (95% CI -169.08 to -94.86) at 3 months (two trials), -135.00 um (95% CI -194.50 to -75.50) at 6 months (one trial), -133.00 um (95% CI -199.86 to -66.14) at 9 months (one trial), and -59.00 um (95% CI -103.50 to -14.50) at 24 months (one trial), all in favor of IVTA. The RR for at least one grade macular edema resolution was 5.15 (95% CI 2.23 to 11.88) at 3 months in favor of IVTA (one trial). Two trials reported improved clinical outcome when FAI was compared to standard of care. Beneficial effect was also observed in one dexamethasone DDS trial. Increased intraocular pressure and cataract formation were side effects requiring monitoring and management. RCTs included in this review suggest that steroids placed inside the eye by either intravitreal injection or surgical implantation may improve visual outcomes in eyes with persistent or refractory DME. Since the studies in our report focused on chronic or refractory DME, the question arises whether intravitreal steroids therapy could be of value in other stages of DME, especially the earlier stages either as standalone therapy or in combination with other therapies, such as laser photocoagulation.

Short-term variation of autorefraction in Diabetic Macular Edema (DME) *

Very few studies have investigated autorefraction in diabetic subjects presenting either with diabetic retinopathy (DR) and/ or diabetic macular edema (DME). To the best of our knowledge this is the first study using multivariate methods for investigating short-term autorefraction in a small sample of subjects diagnosedwith DME. Forty consecutive autorefractor measurements were taken over a short interval on each of seven diabetic subjects with varying stages of DME, and the results were compared to a smaller group of four diabetic control subjects without DME (reasons for the differences in sample sizes will be explained later). Measurements were obtained from both the right and left eyes of all subjects. Subjects in the two groups were similarly matched according to duration of diabetes mellitus (DM), age and glycated hemoglobin (HbA1c) values. Normality of data distribution was mostly achieved with the removal of outliers (where necessary) until profiles of skewness, kurtosis, and standard mean deviation exhibited near-normal distribution. Thereafter, stereo-pair scatter plots with 95% surfaces of constant probability density (distribution ellipsoids) were generated and compared between the experimental and control subjects.The diabetic subjects with DME demonstrated a larger spread of measurements in the eyes with the more severe DME, with the exception of one subject (subject 5). The volumes and orientation of the distribution ellipsoids also differed between the subject’s eyes. Some eyes with severe DME and poor visual acuitydisplayed more stigmatic variation (for example, subjects 2 and 4), while others (subjects 1 and 3) displayed more ortho-antistigmatic variation or near oblique antistigmatic variation (subject 7). In all experimental subjects, with the exception of subject 5, the eye with the more severe DME had a larger distribution ellipsoidvolume, indicating greater variation in autorefraction and thus it might be surmised that this paper provides some preliminary data to suggest that diabetic subjects with DME display greater short-term variation of refractive behaviour when compared to diabetic subjects without DME. Secondly, in diabetic subjects withDME, eyes with the more severe DME or worse VA also display greater variation of refractive status. However, there seemed to be no distinctive or obvious pattern to the type of variation.In addition, a suitable statistic in terms of a Cubic Root Difference (CRD) was introduced in this study to compare inter-ocular ellipsoidal volumes. This statistic is also useful for comparing variances between eyes, or between means for groups of eyes, and could be used in studies involving anisometropia, et cetera. Nevertheless, this study suggests that further investigation remains necessary before autorefraction can be used effectively in the early diagnosis, monitoring, and assessment of eyes with diabetic-related complications to the macular regions.

An Extension of the Early Treatment Diabetic Retinopathy Study (ETDRS) System for Grading of Diabetic Macular Edema in the Astemizole Retinopathy Trial

Purpose: To compare the effects of astemizole, an antihistamine, versus placebo on the 1-year course of diabetic macular edema (DME) and to illustrate use of a modified ETDRS system for grading areas of retinal thickening and hard exudates that may be useful in clinical trials of treatments for this disorder. Methods: Between June 1994 and September 1997, at 2 clinics, 63 patients who had, in at least one eye (the study eye), DME that had not previously been treated with macular photocoagulation, and for which photocoagulation was not currently recommended by the investigator, were enrolled and randomly assigned to astemizole or placebo. Fifty-four of the 63 patients (86%, 26 in Clinic 1 and 28 in Clinic 2) completed 1 year of followup and had adequate 7-field stereoscopic film-based color fundus photographs of the study eye at the baseline and 1-year visits. DME was > 0.33 disc diameters (DD) from the center of the macula in 48% of study eyes and involved the center in 13%. Photographs were graded using the ETDRS protocol modified to allow estimates of areas of retinal thickening (RT) and hard exudate (HE) to be made on continuous scales in disc area (DA) units. Principal outcome measures were mean change in the square root of RT area (the average diameter of the area in DD), mean change in area of HE, and change in the degree to which RT involved or threatened the center of the macula. Results: At baseline, RT area in the 54 study eyes ranged from 0.09 to 4.0 DA (median 1.1). At the 1-year visit the square root of RT area (RTdd) had decreased by ≥ 0.3 DD in 10 eyes, increased by ≥ 0.3 DD in 19 and was about the same in 25. Mean change at 1 year was +0.09 DD (SD 0.57) for astemizole versus +0.19 DD (SD 0.48) for placebo, for a difference of −0.10 DD (95% CI −0.38, +0.19; p = 0.51). Adjustments for baseline and time-dependent risk factors did not change this result appreciably, although there was a trend towards a difference in favor of astemizole in the subgroup of patients with more severe retinopathy. Other morphologic outcomes paralleled change in RTdd. Change in RTdd did vary by clinic: −0.03 DD in Clinic 2, versus + 0.32 DD in Clinic 1, for a difference of −0.35 DD (95% CI −0.62, −0.07; p = 0.014). Clinic 1 is a tertiary retinal referral center in Pennsylvania and Clinic 2 a retinal clinic closely affiliated with a large diabetes clinic in Copenhagen. The unexpected clinic difference in outcome provided an opportunity for further analyses using the modified ETDRS system. In comparison to Clinic 1, Clinic 2 patients were more often male, were younger at diagnosis of diabetes, and had less severe retinopathy and better visual acuity, but these differences did not appear to explain the trend for lesser increase in RTdd. Conclusion: No effect of astemizole was found, but the confidence interval for the principal outcome, mean change in RTdd, included both a modest beneficial effect and a small harmful effect. This outcome measure did demonstrate a small difference in outcome by clinic, which could not be explained by baseline characteristics but may reflect differences in access to and/or continuity of care or other unmeasured differences associated with different referral patterns. Although optical coherence tomography may supplant photography as a measure of central RT, photographic assessments of change in RT and HE areas analyzed with the methods described herein may be useful outcomes in trials assessing treatment of early stages of DME. Application of these methods to other data sets is needed to confirm this conclusion.