Diabetic Macular Edema Eyes Research Articles

Foveal thickness reduction after anti-vascular endothelial growth factor treatment in chronic diabetic macular edema.

To report foveal thickness reduction in eyes with resolution of macular edema and recovery of a foveal depression after one-year of anti-vascular endothelial growth factor (anti-VEGF) therapy for center-involving diabetic macular edema (DME). Foveal thickness was assessed with optical coherence tomography to determine the central subfield foveal thickness (CSFT) and macular volume in 42 eyes with DME (CSFT>275 µm). Evaluations also included measurement of best-corrected visual acuity (BCVA), and were performed at baseline, and upon foveal depression recovery achieved after 12 monthly intravitreal injections of either 1.5 mg/0.06 mL bevacizumab (n=21) or 0.5 mg/0.05 mL ranibizumab (n=21). Data was compared to 42 eyes of normally sighted, non-diabetic, healthy individuals with similar age, gender and race distributions. Mean baseline BCVA was 0.59±0.04 and 0.32± 0.03 logMAR (P<0.001) after treatment and resolution of DME, with all, but 3 eyes, showing BCVA improvement. Mean CSFT before treatment was 422.0±20.0 µm, and after treatment, decreased to 241.6±4.6 µm (P<0.001), which is significantly thinner than CSFT found in control subjects (272.0±3.4 µm; P<0.001). Moreover, in 33/42 DM eyes (79%), CSTF was thinner than the matched control eye. Macular volume showed comparable results, but with lower differences between groups (control: 8.5±0.4 mm3; DME: 8.2±1.0 mm3; P=0.0267). DME eyes show significantly lower foveal thickness than matched controls after DME resolution achieved with one-year anti-VEGF therapy. Further investigation into the reasonsfor this presumable retinal atrophy using fluorescein angiography and functional parameters as well as establishing possible predictors is warranted. This finding should be considered during the treatment of DME.

Predictive factors of better outcomes by monotherapy of an antivascular endothelial growth factor drug, ranibizumab, for diabetic macular edema in clinical practice.

Intravitreal ranibizumab (IVR) has been approved for treating diabetic macular edema (DME), and is used in daily clinical practice. However, the treatment efficacies of IVR monotherapy in real-world clinical settings are not well known.The medical records of 56 eyes from 38 patients who received their first IVR for DME between April 2014 and March 2015, and were retreated with IVR monotherapy as needed with no rescue treatment, such as laser photocoagulation, were retrospectively reviewed. The clinical course, best-corrected visual acuity (BCVA), and fundus findings at baseline, before the initial IVR injection, and at 12 months, were evaluated.Twenty-five eyes from 25 patients (16 men; mean age 68.7 ± 9.8 years) who received IVR in the first eye, or unilaterally, without any other treatments during follow-up were included. After 12 months, mean central retinal thickness (CRT), which includes edema, was reduced (P = .003), although mean BCVA remained unchanged. There was a negative correlation between individual changes in BCVA (r = −0.57; P = .003) and CRT (r = −0.60; P = .002) at 12 months compared with baseline values. BCVA changes were greater in individuals with a history of pan-retinal photocoagulation at baseline (P = .026). After adjusting for age and sex, CRT improvement >100 μm at 12 months was associated with a greater CRT at baseline (OR 0.87 per 10 μm [95% CI 0.72–0.97]; P = .018) according to logistic regression analyses; however, better BCVA and CRT at 12 months were associated with a better BCVA (r = 0.77; P < .001) and lower CRT (r = 0.41; P = .039) at baseline, respectively, according to linear regression analyses.IVR monotherapy suppressed DME, and the effects varied according to baseline conditions. Eyes that had poorer BCVA or greater CRT, or a history of pan-retinal photocoagulation at baseline, demonstrated greater improvement with IVR monotherapy. In contrast, to achieve better outcome values, DME eyes should be treated before the BCVA and CRT deteriorate. These findings advance our understanding of the optimal use of IVR for DME in daily clinical practice, although further study is warranted.

Intravitreal aflibercept versus intravitreal ranibizumab for the treatment of diabetic macular edema.

PurposeThe purpose of this study was to compare the efficacy of intravitreal aflibercept and ranibizumab in the treatment of diabetic macular edema (DME) in eyes with moderate visual loss.Patients and methodsThis study is a randomized prospective study. Seventy eyes with DME were divided into two groups (each containing 35 eyes). Eyes in group I were treated with intravitreal injection of 2 mg/0.05 mL aflibercept and eyes in group II were treated with intravitreal injection of 0.5 mg/0.1 mL ranibizumab. All the eyes had three successive injections as a loading dose (with 1 month interval), and then the patients were followed up monthly for 12 months. The outcomes of the study were visual acuity, central macular thickness (CMT), and the number of re-injections of the drug.ResultsMean age of the patients in group I was 55.05±4.7 years and in group II was 56.64±5.8 years (P=0.17). The mean baseline best corrected visual acuity (BCVA) of eyes treated with aflibercept was 0.17±0.05 and with ranibizumab was 0.18±0.04 (P=0.9). BCVA was improved in both the groups at the end of the follow-up period and was found to be 0.42±0.28 and 0.37±0.23, respectively (P=0.27). The mean baseline CMT of eyes in group I was 465.29±33.7 µm and in group II was 471.5±34.4 µm (P=0.65). CMT decreased in both the groups to 360.8±85.7 µm and 387.3±87.8 µm, respectively (P=0.2). The mean number of drug re-injection was 2.62±0.68 and 3.03±0.95 in both the groups, respectively (P=0.02).ConclusionAflibercept and ranibizumab have the same efficacy in the treatment of DME in eyes with moderate visual loss but with less number of drug re-injection and less treatment burden with aflibercept (2.62±0.68 versus 3.03±0.95).

Prediction of Anti-VEGF Response in Diabetic Macular Edema After 1 Injection.

With multiple anti-vascular endothelial growth factor and steroid therapies available for diabetic macular edema (DME), there is a need for early determination of the best treatment for a particular patient to prevent irreversible vision loss from chronic DME. In this study, we classify patients as responders or non-responders to anti-vascular endothelial growth factor (VEGF) monotherapy in the treatment of DME after a single anti-VEGF injection. The study was designed as a single center, retrospective, interventional case series. We included patients who received 3 consecutive monthly injections with the same anti-VEGF agent. We excluded patients who were treated for DME in the preceding 3 months with any form of anti-VEGF therapy. Visual acuity and central retinal thickness (CRT) data were followed for one year. Receiver operating characteristic (ROC) curve analysis was performed in order to identify cutoff values for identifying responders. 107 eyes were reviewed, with 40 eyes of 34 patients meeting all inclusion criteria. Based on ROC curve analysis, a reduction in CRT by > 15% at 1-month, identified eyes that responded to treatment and had a >25% reduction in CRT at 3-months (sensitivity 0.75, specificity 0.92). DME eyes that have early response to anti-VEGF treatment by reduction in CRT will have significant response to treatment by 3 months.

The incidence and risk factors for the development of vitreomacular interface abnormality in diabetic macular edema treated with intravitreal injection of anti-VEGF.

PurposeTo report the incidence and associated factors for the development of vitreomacular interface abnormality (VMIA) in patients with diabetic macular edema (DME) who received intravitreal injection (IVI) of anti-VEGF (Bevacizumab and Ranibizumab) treatment.MethodsA retrospective observational study. Patients with DME followed at least 6 months were reviewed. Baseline best-corrected visual acuity (BCVA), central retinal thickness (CRT) and final BCVA, CRT in eyes with and without VMIA were compared. Multiple logistic regression was also used to investigate the risk factors of VMIA formation in patients with DME treated by anti-VEGF.ResultsA total of 201 eyes in 142 patients met the inclusion criteria of the study. VMIA developed in 44 eyes (21.89%) of patients during a mean follow-up period of 40.84 months. The estimated mean incidence of VMIA formation was 6.43% per year. Poor baseline BCVA was found to be a risk factor for VMIA development (P=0.001, odds ratio=5.299, 95% confidence interval: 1.972 to 14.238). There was no difference between eyes with and without VMIA formation in improving BCVA (P=0.557) and lowering the macular edema (eyes without VMIA formation: -107.72±171.91 μm; eyes with VMIA formation: -155.02±212.27 μm, P=0.133).ConclusionsThis study revealed the incidence of VMIA formation in IVI anti-VEGF treated DME eyes was 6.43%. Poor baseline BCVA was found to be a risk factor for VMIA formation. Both eyes with and without VMIA development had favorable response to anti-VEGF treatment.

Optical Coherence Tomography Angiography of DME and Its Association with Anti-VEGF Treatment Response

To investigate the structural integrity of the superficial capillary plexuses (SCPs) and deep capillary plexuses (DCPs) using optical coherence tomography (OCT) angiography (OCTA) in patients with diabetic macular edema (DME) and its association with the response to anti-vascular endothelial growth factor (VEGF) treatment. Retrospective, case-control study. We included 51 DME eyes with a poor response to anti-VEGF agents and 32 age-matched DME eyes with a good response to anti-VEGF treatment, along with 20 fellow eyes without DME from the cases and controls. The medical records, including OCTA and spectral-domain OCT (SD OCT), were reviewed and compared between the groups. En face OCTA images of the SCP and DCP were obtained for each eye. An anti-VEGF responder was defined by a reduction of more than 50 μm in central retinal thickness after 3 consecutive anti-VEGF treatments. A poor responder was defined by a reduction of less than 50 μm or an increase in central retinal thickness after 3 monthly injections. We measured the vascular density and foveal avascular zone (FAZ) area and counted the number of microaneurysms in each layer. The SD OCT images were compared with OCTA findings. Compared with non-DME eyes, DME eyes had a lower vascular density (P < 0.001) and larger FAZ area (P < 0.001) in the DCP and more microaneurysms (P < 0.001) in both layers. Although there was no significant difference in the SCP between anti-VEGF responders and poor responders, poor responders tended to show greater damage and more microaneurysms in the DCP (P < 0.001) and a larger FAZ area (P < 0.001). The topographic location of the disrupted synaptic portion of the outer plexiform layer (OPL) in SD OCT exactly corresponded to the nonflow area of the DCP in OCTA. Compared with DME eyes that responded to anti-VEGF treatment, poor responders show significant damage to the integrity of the DCP, but not the SCP. The degree of OPL disruption in SD OCT corresponds well with the extent of DCP loss in DME eyes. The extent of DCP loss and the corresponding OPL disruption could be useful predictors of responsiveness to anti-VEGF treatment.

Dynamic functionality and static changes of retinal vessels in diabetic patients treated with intravitreal ranibizumab.

To investigate the short-term effects of intravitreal ranibizumab on retinal vessel functionality in patients with diabetic macular edema (DME) by Dynamic Vessel Analyzer (DVA). Patients presenting with DME were enrolled in the study. All patients underwent a complete ophthalmic evaluation, including optical coherence tomography and dynamic and static vessel analysis, using the DVA before (baseline), 1week and 1month after administration of intravitreal ranibizumab. DME subject were compared with diabetic retinopathy (DR) without DME subjects, and with normal non diabetic subjects (controls) matched for age and sex. A total of 45 eyes of 45 subjects (15 eyes for each group) were included in the analysis. In DME patients, dynamic analysis showed a significant decrease in mean arterial dilation from baseline to 1week. Mean central retinal artery equivalent (CRAE) of DR patients without DME was significantly different from baseline and week 1 of DME eyes. In healthy control subjects, CRAE was significantly different from CRAE at baseline and 1week on DME patients, but not significantly different from DR patients without DME. Using DVA in patients with DME, dynamic analysis showed a significant decrease in mean arterial dilation from baseline to 1week in DME eyes. A significant reduction in arterial vessels could be demonstrated in DME patients compared to DR patients without DME and controls.

Aflibercept for Diabetic Macular Edema in Eyes Previously Treated With Ranibizumab and/or Bevacizumab May Further Improve Macular Thickness.

To evaluate the short-term anatomic and visual outcomes after aflibercept (Eylea; Regeneron, Tarrytown, NY) in eyes with diabetic macular edema (DME) previously treated with ranibizumab (Lucentis; Genentech, South San Francisco, CA) and/or bevacizumab (Avastin; Genentech, South San Francisco, CA). A single-center, retrospective, noncomparative study of 30 eyes in 23 patients with DME treated with prior ranibizumab and/or bevacizumab before switching to aflibercept. Eyes received an average of 16 prior injections (range: three injections to 31 injections; median: 17 injections). The mean central subfoveal thickness (CST) improved from 453 µm at the time of first anti-vascular endothelial growth factor (VEGF) injection (range: 304 µm to 686 µm; median: 429 µm), to 374 µm at the time of the switch to aflibercept (range: 267 µm to 547 µm; median: 361 µm; P = .02), to 332 µm after the first aflibercept injection (range: 242 µm to 545 µm; median: 318 µm; P < .001). Visual acuity improved after switching to aflibercept at the first follow-up visit (logMAR 0.40 [Snellen equivalent 20/50]) to logMAR 0.35 (Snellen equivalent 20/45) (P = .044). In eyes with persistent DME treated with ranibizumab and/or bevacizumab, switching to aflibercept may further improve macular thickness. Given the cost difference between the three drugs, a randomized trial evaluating a stepwise approach may be worthwhile. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:836-839.].

Comparison of the Effectiveness of Intravitreal Ranibizumab for Diabetic Macular Edema in Vitrectomized and Nonvitrectomized Eyes

Purpose: To compare the effectiveness of intravitreal ranibizumab (IVR) for diabetic macular edema (DME) between eyes with and without previous vitrectomy. Procedures: We prospectively assessed the best-corrected visual acuity (BCVA) and central macular thickness (CMT) after IVR for 6 months. Results: There were no significant differences in the baseline BCVA and CMT between both groups. In the nonvitrectomized group (n = 15), the mean changes of BCVA and CMT from baseline to month 6 were significant (p < 0.01). In the vitrectomized group (n = 10), the improvement appeared to be slower, and the mean BCVA improvement was not significant (p = 0.5), although the mean CMT decrease was significant (p < 0.05). There were no significant differences in the mean changes of BCVA and CMT between both groups at 6 months. Conclusions: The difference in the effectiveness of IVR between both groups was not significant. IVR can be a treatment option even for vitrectomized DME eyes.

Subfoveal choroidal thickness changes after intravitreal bevacizumab injection for neovascular age-related macular degeneration and diabetic macular edema.

The purpose of this study was to investigate the changes in subfoveal choroidal thickness (SFCT) after intravitreal injection of bevacizumab (IVB) for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME). This retrospective, consecutive, interventional case series study included 43 eyes [21 affected eyes with neovascular AMD (AMD group) and 22 affected eyes with DME (DME group)] which were treated with 1.25mg/0.5ml IVB and 43 untreated fellow eyes of 43 patients. SFCT was measured in all 86 eyes at baseline before IVB injection and at day 1, week 1, and month 1 after injection by use of enhanced depth imaging optical coherence tomography (EDI OCT). Central foveal thickness (CFT) and best-corrected visual acuity were analyzed at baseline and during follow-up visits. Main outcome measure was change in SFCT in 1month after treatment. All 43 eyes treated with IVB showed a significant reduction in SFCT. Mean SFCT in treated eyes decreased from 237.1±75.3µm at baseline to 214.0±65.7µm at day 1, 205.4±59.7 at week 1, and 222.7±73.3 at month 1, whereas SFCT in fellow eyes changed from 228.4±63.6 at baseline to 224.5±68.5 at day 1, 220.4±72.1 at week 1, and 226.9±74.0 at month 1. SFCT demonstrated a similar trend toward decrease in both groups. CFT decreased significantly and visual acuity improved significantly. SFCT decreased significantly in AMD and DME eyes following injection. The decreasing effect of bevacizumab on choroidal thickness was highest at first week and continued to the end of first month after injection.

RANIBIZUMAB PLUS PROMPT OR DEFERRED LASER FOR DIABETIC MACULAR EDEMA IN EYES WITH VITRECTOMY BEFORE ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

The approach to managing diabetic macular edema in eyes with previous vitrectomy is based on limited evidence. Therefore, an exploratory post hoc assessment of 3-year data from eyes with and without vitrectomy before randomization in a DRCR.net trial that evaluated ranibizumab + prompt or deferred laser for diabetic macular edema is presented. Visual acuity and optical coherence tomography outcomes were compared between eyes with and without previous vitrectomy. At baseline, eyes with previous vitrectomy (n = 25) had longer duration of diabetes, worse visual acuity, less thickened central subfield measurements on optical coherence tomography and were more apt to have worse diabetic retinopathy severity level or previous treatment for macular edema or cataract surgery than eyes without a history of vitrectomy (n = 335). Analyses adjusted for these baseline imbalances did not identify substantial differences between eyes with and without previous vitrectomy at each annual visit through 3 years for the favorable visual acuity, optical coherence tomography central subfield thickness, or volume outcomes, although optical coherence tomography improvement appeared slower in vitrectomy eyes during the first year. This study provides little evidence that the beneficial clinical outcomes for patients with center-involved diabetic macular edema treated with anti-vascular endothelial growth factor are affected in the long term by previous vitrectomy.

Switching to ranibizumab for diabetic macular edema with persistent fluid on bevacizumab: Who is likely to benefit from the switch?

PurposeTo evaluate the efficacy of switching from bevacizumab to ranibizumab in patients with diabetic macular edema (DME).MethodsThe medical records of 41 DME eyes which showed persistent fluid after at least three monthly bevacizumab injections, and switched to ranibizumab injection were reviewed. Each patient received a single ranibizumab injection and followed up at 1 month. Anatomic responders to ranibizumab were followed up monthly and given ranibizumab injections on an as‐needed basis until 3 months.ResultsAt 1 month, the mean central foveal thickness (CFT) decreased from 431 μm to 349 μm (P &lt; .001), and mean best‐corrected visual acuity (BCVA) improved from 20/53 to 20/48 (P = .062). Twenty‐six eyes (65.9%) were classified as anatomical responders, and the mean CFT improved and maintained until 3 months (439 μm to 320 μm, P &lt; .001) after repeated injections (mean number: 2.8), while the mean BCVA stabilized (20/59 to 20/54, P = .075) in these eyes. Dry macula were achieved in 9 of 26 eyes at least once during the follow‐up period. Favorable anatomic response to ranibizumab at month 1 was related with previous partial response to bevacizumab.ConclusionsSwitching to ranibizumab may present an alternative option in the treatment of DME with persistent fluid after repeated bevacizumab injections, and the switch was more effective in eyes that showed partial response to previous bevacizumab.

Efficacy of dexamethasone intravitreal implant for the treatment of diabetic macular edema.

To assess the efficacy of a single dexamethasone intravitreal implant (Dex-I) injection for the treatment of diabetic macular edema (DME). This was a retrospective chart review of 39 eyes (34 consecutive patients). Best-corrected visual acuity (BCVA), central macular thickness (CMT), and increase in intraocular pressure (IOP) (gt;24 mm Hg) were analyzed before treatment and 2 and 4 months after injection. Preoperative mean CMT was 559 ± 111 μm and decreased to 338 ± 84 and 477 ± 140 μm 2 and 4 months after injection, respectively. Although all eyes showed a significant decrease in CMT 2 months after injection (p&lt;0.0001), a recurrence of the macular edema was observed 4 months after injection in 79% of eyes. Mean BCVA improvement (logMAR) was 0.13 ± 0.18 (p&lt;0.0001) and 0.07 ± 0.21 (p = 0.049) 2 and 4 months after injection, respectively, without significant difference between vitrectomized and nonvitrectomized eyes. Eight eyes (21%) developed reversible increase in IOP 2 months after injection. Thirty percent of DME eyes had gained more than 2 logMAR lines 2 months after Dex-I injection and safety was good. Visual acuity gain was maintained 4 months after injection despite a recurrence of edema in most cases.

Real-world assessment of intravitreal dexamethasone implant (0.7 mg) in patients with macular edema: the CHROME study.

BackgroundThe purpose of this study was to evaluate the real-world use, efficacy, and safety of one or more dexamethasone intravitreal implant(s) 0.7 mg (DEX implant) in patients with macular edema (ME).MethodsThis was a retrospective cohort study of patients with ME secondary to retinal disease treated at ten Canadian retina practices, including one uveitis center. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), glaucoma and cataract surgery, and safety data were collected from the medical charts of patients with ≥3 months of follow-up after the initial DEX implant.ResultsOne hundred and one patient charts yielded data on 120 study eyes, including diagnoses of diabetic ME (DME) (n=34), retinal vein occlusion (RVO, n=30; branch in 19 and central in 11), and uveitis (n=23). Patients had a mean age of 60.9 years, and 73.3% of the study eyes had ME for a duration of ≥12 months prior to DEX implant injection(s). Baseline mean (± standard error) BCVA was 0.63±0.03 logMAR (20/86 Snellen equivalents) and mean CRT was 474.4±18.2 μm. The mean number of DEX implant injections was 1.7±0.1 in all study eyes; 44.2% of eyes had repeat DEX implant injections (reinjection interval 2.3–4.9 months). The greatest mean peak changes in BCVA lines of vision occurred in study eyes with uveitis (3.3±0.6, P<0.0001), followed by RVO (1.3±0.5, P<0.01) and DME (0.7±0.5, P>0.05). Significant decreases in CRT were observed: −255.6±43.6 μm for uveitis, −190.9±23.5 μm for DME, and −160.7±39.6 μm for RVO (P<0.0001 for all cohorts). IOP increases of ≥10 mmHg occurred in 20.6%, 24.1%, and 22.7% of DME, RVO, and uveitis study eyes, respectively. IOP-lowering medication was initiated in 29.4%, 16.7%, and 8.7% of DME, RVO, and uveitis study eyes, respectively. Glaucoma surgery was performed in 1.7% of all study eyes and cataract surgery in 29.8% of all phakic study eyes receiving DEX implant(s).ConclusionDEX implant(s) alone or combined with other treatments and/or procedures resulted in functional and anatomic improvements in long-standing ME associated with retinal disease.

Safety of transfoveal subthreshold diode micropulse laser for fovea-involving diabetic macular edema in eyes with good visual acuity.

To determine the safety of transfoveal subthreshold diode micropulse laser for fovea-involving diabetic macular edema. The records of all patients treated with transfoveal subthreshold diode micropulse laser for fovea-involving diabetic macular edema in two retina clinics were reviewed. The eligibility included fovea-involving diabetic macular edema by spectral domain optical coherence tomography and pretreatment visual acuity of 20/40 or better. Thirty-nine eyes of 27 patients aged 50 years to 87 years (mean, 69 years) were included. Postoperative follow-up ranged from 3 months to 36 months (mean, 11 months). Fourteen patients were insulin dependent, and 19 had nonproliferative retinopathy. The preoperative visual acuity was 20/20 (10 eyes), 20/25 (10 eyes), 20/30 (8 eyes), and 20/40 (11 eyes). No eye had evidence of laser-induced macular damage by any imaging means postoperatively. There were no adverse treatment effects. Logarithm of the minimum angle of resolution visual acuity was improved on average of 0.03 units at 4 months to 7 months of follow-up (P = 0.0449, paired t-test) and otherwise stable. The central foveal thickness was improved at 4 months to 7 months (P = 0.05, paired t-test) and 8 months to 12 months, postoperatively (P = 0.04, mixed model accounting). Maximum macular thickness was improved at 4 months to 7 months postoperatively (P = 0.01, paired t-test and mixed model accounting). In a small retrospective series, transfoveal subthreshold diode micropulse laser was safe and effective for the treatment of fovea-involving diabetic macular edema in eyes with good preoperative visual acuity that were not the candidates for conventional photocoagulation or intravitreal injection. Further study is warranted.

Three-Dimensional Automated Choroidal Volume Assessment on Standard Spectral-Domain Optical Coherence Tomography and Correlation With the Level of Diabetic Macular Edema

To measure choroidal thickness on spectral-domain optical coherence tomography (SD OCT) images using automated algorithms and to correlate choroidal pathology with retinal changes attributable to diabetic macular edema (DME). Post hoc analysis of multicenter clinical trial baseline data. SD OCT raster scans/fluorescein angiograms were obtained from 284 treatment-naïve eyes of 142 patients with clinically significant DME and from 20 controls. Three-dimensional (3D) SD OCT images were evaluated by a certified independent reading center analyzing retinal changes associated with diabetic retinopathy. Choroidal thicknesses were analyzed using a fully automated algorithm. Angiograms were assessed manually. Multiple endpoint correction according to Bonferroni-Holm was applied. Main outcome measures were average retinal/choroidal thickness on fovea-centered or peak of edema (thickest point of edema)-centered Early Treatment Diabetic Retinopathy Study grid, maximum area of leakage, and the correlation between retinal and choroidal thicknesses. Total choroidal thickness is significantly reduced in DME (175 ± 23 μm; P = .0016) and nonedematous fellow eyes (177 ± 20 μm; P = .009) of patients compared with healthy control eyes (190 ± 23 μm). Retinal/choroidal thickness values showed no significant correlation (1-mm: P = .27, r(2) = 0.01; 3-mm: P = .96, r(2) < 0.0001; 6-mm: P = .42, r(2) = 0.006). No significant difference was found in the 1- or 3-mm circle of a retinal peak of edema-centered grid. All other measurements of choroidal/retinal thickness (DME vs healthy, DME vs peak of edema-centered, DME vs fellow, healthy vs fellow, peak of edema-centered vs healthy, peak of edema-centered vs fellow eyes) were compared but no statistically significant correlation was found. By tendency a thinner choroid correlates with larger retinal leakage areas. Automated algorithms can be used to reliably assess choroidal thickness in eyes with DME. Choroidal thickness was generally reduced in patients with diabetes if DME is present in 1 eye; however, no correlation was found between choroidal/retinal pathologies, suggesting different pathogenetic pathways.

Subclinical Macular Edema as a Predictor of Progression to Clinically Significant Macular Edema in Type 2 Diabetes

Objective: To examine the relationship between subclinical diabetic macular edema (DME) and the development of clinically significant macular edema (CSME) in nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes. Methods: A prospective, monocenter, observational study was designed to follow patients/eyes with type 2 diabetes and NPDR (Early Treatment Diabetic Retinopathy Study levels 20 and 35) with no prior laser treatment for 2 years or until development of CSME. Ophthalmologic examinations, including best-corrected visual acuity, fundus photography and optical coherence tomography (OCT), were performed at baseline, 6 months and a final visit. Results: A total of 348 patients completed study follow-up; 26 eyes developed CSME. Six out of 32 eyes/patients presenting subclinical DME at baseline developed CSME (18.7%), while 20 out of 316 eyes without subclinical DME developed CSME (6.3%). Eyes/patients with subclinical DME presented a risk for DME progression 3.686 times higher than that of eyes/patients without subclinical DME (95% confidence interval 1.221-7.988). Conclusions: Subclinical DME in eyes with NPDR identified by center point thickness measured on a Stratus OCT is a good predictor of CSME development.

EFFECTS OF SOLUBLE CD14 AND CYTOKINE LEVELS ON DIABETIC MACULAR EDEMA AND VISUAL ACUITY

The pathogenesis of diabetic retinopathy has been suggested to be associated with ocular inflammation. Macrophages and monocytes that infiltrate the eye are known to express CD14. After shedding from the membrane-bound CD14, soluble CD14 (sCD14) is released, which could potentially activate inflammatory signaling. In this study, the authors investigated ocular fluid and serum levels of vascular endothelial growth factor (VEGF), sCD14, and other inflammatory cytokines in patients with diabetic macular edema (DME). Furthermore, the authors determined any potential correlation between these factors and visual acuity. Vitreous fluid, aqueous humor, and serum samples from 14 eyes with DME and 24 control eyes were investigated. Soluble CD14, interleukin 8, interferon-inducible protein 10, monocyte chemotactic protein 1, monokine induced by interferon γ, and VEGF were measured simultaneously by FACSCalibur flow cytometer. Visual acuity was measured in all patients with DME before surgery, with the assessors being blinded to the patients' diagnoses. All factors were significantly elevated in vitreous fluid of DME eyes. Soluble CD14 and VEGF levels in vitreous fluid and aqueous humor were significantly higher in patients with DME than in nondiabetic controls (P < 0.05). In patients with DME, vitreous and aqueous humor concentrations of sCD14 correlated significantly. In these patients, vitreous fluid concentration of sCD14 correlated significantly with that of VEGF or interleukin 8 or monocyte chemotactic protein 1. In addition, there was a significant positive correlation between preoperative visual acuity and intraocular sCD14 concentrations. Soluble CD14 may act as key regulator of VEGF production and contribute to the pathogenesis of diabetic retinopathy.

Blood‐retinal barrier function status from OCT data

AbstractPurpose To demonstrate the presence of blood‐retinal barrier (BRB) function information within OCT data.Methods It was recently suggested that OCT data embeds functional information on BRB status. In this work a different approach was followed resorting to the use of support vector machines (SVM) to discriminate between healthy (N=31), ETDRS level 10 diabetic retinopathy (DR) (N=31) and diabetic macular edema (DME) eyes (N=31). Healthy volunteers and diabetic patients underwent Cirrus HD‐OCT (Carl Zeiss Meditec, Dublin, USA) using both the 512x128 and the 200x200 Macular Cube Protocols. Data was exported and the intensity distributions were computed for each eye, taking into consideration only the retina (between the inner limiting membrane ILM and the retinal pigment epithelium RPE), both on the logarithmic and linear spaces. A total of 43 parameters per eye were computed and labeled accordingly (healthy, DR and DME). A publicly available SVM toolbox (LIBSVM) was applied to assess the possibility of discriminating between each of these groups using a radial basis function (RBF) kernel and the leave‐one‐out approach for validation.Results Achieved results allow to conclude on the possibility of discriminating between healthy and DR eyes (level 10 ETDRS and DME eyes). Of added value is the fact the system is able to discriminate between healthy and ETDRS level 10 DR eyes. This suggests that optical properties of the retina are modified and that this change cannot be currently detected using any other available technique.Conclusion In this work, it was demonstrated the presence of early changes in the optical properties of the human retina related to diabetes, and that this information is embedded in OCT data. Support: FCT/PTDC/SAU‐BEB/103151/2008

Intravitreal gas injection for the treatment of diabetic macular edema

PurposeThis study investigates the efficacy of an intravitreal gas injection in inducing a posterior vitreous detachment (PVD) in patients with clinically significant diabetic macular edema refractory to laser therapy.MethodsA local ethics committee-approved technique of an intravitreal injection of pure perfluoropropane gas (C3F8) was performed for all participants. After a period of prone positioning, the patients underwent regular and detailed clinical review.Main outcome measuresThe induction of a PVD, change in macular thickness, change in visual acuity.ResultsA PVD was induced in all five eyes with subsequent signs of reduction in macular thickness and resolution of exudates. Mean visual improvement was 11 ETDRS (Early Treatment Diabetic Retinopathy Study) letters (range 4–21). Apart from a transient vitreous hemorrhage in one eye, there were no significant treatment-related complications.ConclusionThe induction of a PVD by pneumatic retinopexy appears to have a significant influence on diabetic macular edema in eyes which have not successfully responded to macular laser therapy. A randomized clinical trial is justified on the basis of the initial promising data.