Clinically Significant Diabetic Macular Edema Research Articles

Evaluation of an AI algorithm trained on an ethnically diverse dataset to screen a previously unseen population for diabetic retinopathy.

This study aimed to determine the generalizability of an artificial intelligence (AI) algorithm trained on an ethnically diverse dataset to screen for referable diabetic retinopathy (RDR) in the Armenian population unseen during AI development. This study comprised 550 patients with diabetes mellitus visiting the polyclinics of Armenia over 10 months requiring diabetic retinopathy (DR) screening. The Medios AI-DR algorithm was developed using a robust, diverse, ethnically balanced dataset with no inherent bias and deployed offline on a smartphone-based fundus camera. The algorithm here analyzed the retinal images captured using the target device for the presence of RDR (i.e., moderate non-proliferative diabetic retinopathy (NPDR) and/or clinically significant diabetic macular edema (CSDME) or more severe disease) and sight-threatening DR (STDR, i.e., severe NPDR and/or CSDME or more severe disease). The results compared the AI output to a consensus or majority image grading of three expert graders according to the International Clinical Diabetic Retinopathy severity scale. On 478 subjects included in the analysis, the algorithm achieved a high classification sensitivity of 95.30% (95% CI: 91.9%-98.7%) and a specificity of 83.89% (95% CI: 79.9%-87.9%) for the detection of RDR. The sensitivity for STDR detection was 100%. The study proved that Medios AI-DR algorithm yields good accuracy in screening for RDR in the Armenian population. In our literature search, this is the only smartphone-based, offline AI model validated in different populations.

Foveal Avascular Zone Does Not Correspond to Choroidal Characteristics in Patients with Diabetic Retinopathy: A Single-Center Cross-Sectional Analysis.

PurposeThe aim of the study was to compare two non-overlapping blood supply systems of the retina to obtain a better insight into the relation between diabetic macular retinopathy and choroidopathy. Specifically, the study focused on the relationships between (1) retinal vascular changes around the fovea in fluorescein angiography (FA) and (2) choroidal thickness, volume and other parameters assessed by optical coherence tomography (OCT).Patients and MethodsThe retrospective cross-sectional single-center study included 210 eyes from 152 patients with diabetic retinopathy (mean age 60.7±12.4 years, 49.3% of women; foveal avascular zone [FAZ] outline: 44.3% grade ≤2, 55.7% grade ≥3). The outline of FAZ, a measure of capillary loss due to ischemic processes, was analyzed on FA according to the Early Treatment Diabetic Retinopathy Study Research Group (ETDRS) standards. The eyes were stratified according to the FAZ outline and size and the presence of clinically significant diabetic macular edema (CSME). Then, resultant groups were compared in terms of the spectral domain OCT parameters: choroidal thickness and volume (within ETDRS subfields), luminal, stromal and total choroidal areas and choroidal vascularity index (based on the foveal scan). Statistical analysis was based on univariate models with the choroidal parameters as independent variables, and age, sex, panretinal photocoagulation, the severity of diabetic retinopathy and CSME as covariates.ResultsNo significant relationships were found between the FAZ outline and area and choroidal characteristics of patients with diabetic retinopathy. In patients without CSME, no correlation was observed between the FAZ area and choroidal characteristics. In patients with CSME, no correlation was found between the FAZ area and choroidal characteristics other than the choroidal vascularity index.ConclusionIn patients with diabetic retinopathy, damage to the macular retinal vasculature (FAZ) does not seem to be associated with changes in the choroidal vasculature, and these two processes appear to occur independently.

35-LB: Reliability of an Artificial Intelligence (AI) Diabetic Retinopathy (DR) Detection System

A prospective study (NCT04302012) evaluated the reliability of the EyeArt AI DR detection system (Eyenuk, Inc.) across repeated examinations, operators, and cameras. Using retinal images from off-the-shelf color fundus retinal cameras, this AI system is intended to detect patient eyes with referable DR (rDR) [moderate non-proliferative DR (NPDR) or higher on the International Clinical DR (ICDR) severity scale or clinically significant diabetic macular edema (CSDME)] and vision-threatening DR (vtDR) [severe NPDR or higher on the ICDR scale or CSDME].A total of 62 subjects with diabetes were enrolled at 2 U.S. primary diabetes care centers and completed digital DR examination using the AI system (including retinal imaging) multiple times. Of these, 31 subjects underwent 12 AI exams for each eye performed by 3 operators on 4 cameras, and another 31 subjects underwent 6 AI exams for each eye performed by 1 operator on 2 cameras. Subjects had a median age of 50 (22-70) years, 42% were female, 79% were White, 6.5% were Black or African-American, and 6.5% were Asian. Mean (± std. dev.) diabetes duration was 12.5 ± 9 years and 66% had type 2 diabetes. Of the 1116 repeated exams (= 31 subjects x 12 exams x 2 eyes/subject + 31 subjects x 6 exams x 2 eyes/subject), 16 eye exams had missing data (due to minor protocol deviations) and 22 eye exams (all from the same subject) did not have sufficient exam quality to rule out presence of disease. Of the remaining 1078 eye exams, 97.5% were in agreement for the referable DR detection results with a majority of the disagreements limited to only 5 eyes. For the vision-threatening DR detection results, 99.5% were in agreement. This study demonstrates that the EyeArt AI system is robust to variations and can be used to reliably detect diabetic retinopathy in non-ophthalmology settings across different operators and cameras. Disclosure E. Ipp: Research Support; Self; Eyenuk, Inc. D.R. Liljenquist: None.

Patterns of morphologic alteration correlate with vision in diabetic macular oedema: a cross-sectional evaluation of patients using the SAVE II protocol.

We sought to describe and evaluate patients with clinically significant diabetic macular oedema (CSME) according to the improved SAVE II protocol and correlate findings with visual acuity and systemic parameters in the outpatient clinic for DR (diabetic retinopathy) management. This was a cross-sectional case series study of patients with CSME, regardless of prior treatment. Visual acuity testing was performed according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol. Optical coherence tomography (OCT) and fluorescence angiography (FA) were performed. All imaging data were evaluated according to an improved version of the SAVE grading protocol for CSME (SAVE II). The main outcome measures were SAVE II oedema types and best-corrected visual acuity. Additional parameters of a blood sample (fasting glucose, haemoglobin A1c, serum creatinine, triglycerides, cholesterol, low-density lipoproteins, and high-density lipoproteins) were taken. In total, 66 eyes of 66 patients were included. The mean age of the patients was 64.9±8.2years. Two eyes were classified as SAVE oedema type 1, 19 eyes as SAVE oedema type 2, 28 eyes as SAVE oedema type 3, and 28 eyes as SAVE oedema type 4, respectively. Central retinal thickness and laboratory parameters were not significantly different between the groups. There was a statistically significant difference in ETDRS visual acuity between the SAVE groups 2 and 4 (p<0.001) with lower vision in group 4. There was no statistically significant difference between oedema types 2 and 3 (p=0.065) and oedema types 3 and 4 (p=0.13). There was a significant correlation between the four defined oedema types and visual acuity. Morphologic findings did not correlate with any of the evaluated blood parameters.

Aqueous humour cytokine changes during a loading phase of intravitreal ranibizumab or dexamethasone implant in diabetic macular oedema.

PurposeTo determine the effect of intravitreal ranibizumab and a dexamethasone implant on aqueous humour cytokine, protein and enzyme levels and to correlate findings to morphologic and functional changes.MethodsIn a prospective, randomized, controlled, double‐blind study, patients with clinically significant diabetic macular oedema (CSME) were randomly allocated to receive either monthly intravitreal injections of ranibizumab (Lucentis, Novartis Pharma) or a single dexamethasone implant (Ozurdex, Pharm‐Allergan) at baseline (BL). Aqueous humour samples were collected at BL and weeks 2, 8 and 20.ResultsThe study included 18 eyes of 18 patients. In the dexamethasone implant group, soluble intercellular adhesion molecule 1 (sICAM‐1) (weeks 2 and 8), CXCL9/monokine induced by gamma interferon (MIG) (weeks 2 and 8), soluble vascular cell adhesion protein 1 (sVCAM‐1) (weeks 2 and 8) and monocyte chemo‐attractant protein 1 (MCP‐1) (week 2) levels were significantly decreased compared with baseline. In the ranibizumab group, placental growth factor (PIGF) (week 2) and vascular endothelial growth factor (VEGF) (week 2 and 8) levels were significantly decreased compared with baseline. No significant changes in central retinal thickness (CRT) or Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) were observed in the Ozurdex group at any time‐points. ETDRS scores significantly increased at week 20 (84.88 ± 8.88 letters) compared with baseline (74.78 ± 14.85 letters), and the CRT decreased significantly at week 4 (381.00 ± 114.64 μm) compared with baseline (440 ± 144 μm) in the Lucentis group.ConclusionThe dexamethasone implant affected the aqueous cytokines and proteins MCP‐1, sICAM‐1, sVCAM‐1 and MIG, whereas ranibizumab treatments reduced VEGF and PIGF levels. Morphological changes may diverge from cytokine changes. Results may indicate a rationale for a combination therapy for CSME using both agents, the dexamethasone implant and repeatedly administered ranibizumab injections.

37-LB: Diabetic Retinopathy (DR) Screening Performance of an Artificial Intelligence (AI) System: Analysis from a Pivotal Multicenter Prospective Clinical Trial

A prospective study (NCT03112005) evaluated DR screening using the EyeArt AI eye screening system against the ETDRS clinical reference standard (CRS). A total of 893 subjects with diabetes were enrolled at 15 U.S. clinical centers and completed 2-field fundus photography for analysis by the EyeArt system and dilated 4-wide field stereo fundus photography for adjudicated expert grading to establish CRS. The EyeArt system provided eye-level results for referable DR (rDR) [moderate non-proliferative DR (NPDR) or higher on the International Clinical DR (ICDR) severity scale or clinically significant diabetic macular edema (CSDME)] and for vision-threatening DR (vtDR) [severe NPDR or higher on the ICDR scale or CSDME]. Out of 1718 eyes with gradable CRS for rDR, 1392 eyes were negative and 326 were positive. Out of 1702 eyes with gradable CRS for vtDR, 1588 were negative and 114 were positive. The EyeArt system was evaluated against CRS for identifying rDR and vtDR under an undilated protocol and a dilate-if-needed protocol (where dilated images were used for subjects with ungradable EyeArt results on undilated images). Results (Table) indicate that the EyeArt AI system compares favorably with the clinical reference standard and meets the predetermined study endpoints for the detection of referable and vision-threatening DR in people with diabetes. Disclosure B.W. Bode: Consultant; Self; ADOCIA, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; Becton, Dickinson and Company, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Eyenuk Inc., Insulet Corporation, National Institutes of Health, Novo Nordisk Inc., Sanofi Research &amp; Development, Senseonics, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US, Senseonics. Stock/Shareholder; Self; AgaMatrix, Glytec, LLC. E. Ipp: Research Support; Self; Eyenuk Inc., Novartis Pharmaceuticals Corporation. V.N. Shah: Advisory Panel; Self; Sanofi US. Consultant; Self; Dexcom, Inc. S.R. Sadda: Consultant; Self; Carl Zeiss Meditec, Centervue, Heidelberg Engineering, Optos. Other Relationship; Self; Nidek. Other Relationship; Spouse/Partner; Topcon. Funding National Institutes of Health (EY027241, EY026864)

Timing of phacoemulsification in relation to intravitreal ranibizumab injection in diabetic patients type 2 with cataract and mild center involved macular edema

Purpose: To compare preoperative ranibizumab (RBZ) 0.5 mg/0.05 ml three-injection protocol to postoperative protocol in cases with center involved macular edema (CiME), undergoing phacoemulsification. Patients and Methods: Cases with non-ischemic clinically significant diabetic macular edema (CSDME) were randomized into two groups. Both groups received three intravitreal RBZ injections on monthly basis. Group 1, received the first two injection 2 months before phacoemulsification and the third one was injected intraoperative by the end of surgey. Group 2 received the first injection intraoperatively followed by 2 other injections, 1 and 2 months postoperatively. Central subfield thickness (CST) was measured using spectral-domain optical coherence tomography (RTvue-100), 1 month after third injection for both groups. Results: The mean postoperative corrected distance visual acuity (CDVA) at 3 months postoperatively was significantly improved (P = 0.005) in Group 1 than in Group 2. The postoperative CST 1 month after the third injection for Group 1 was 252.5 μm ± 16 versus 270.1 μm ± 24.4 for Group 2, which was statistically significant (P = 0.02). Percentage of reduction in central foveal thickness (CFT) was 15.4% and 8%, Groups 1 and 2, respectively. The ellipsoid zone integrity showed Interruption in Group 1 in 19.4% of eyes, which was lower than in Group 2 (28%), however this was not statistically significant (P = 0.4). None of our cases developed epiretinal membranes in either groups. In Group 2 only, four cases developed subretinal fluid (SRF), and one case had cystoid changes. None of the cases developed SRF or de novo cystoid changes, till the last follow-up visit, in Group 1. Conclusion: Using RBZ repeated intravitreal injections protocol prior to phacoemulsification improved significantly CDVA and reduced the CST, than when injected postoperatively. In addition, the number of postoperative intravitreal injections that might be needed was significantly reduced when it is used preoperatively.

Flavoprotein Fluorescence Correlation with Visual Acuity Response in Patients Receiving Anti-VEGF Injection for Diabetic Macular Edema.

Anti-VEGF treatment of diabetic macular edema (DME) complicating diabetic retinopathy (DR) has greatly improved structural and visual outcomes for patients with diabetes mellitus. However, up to 50% of patients are either nonresponsive or refractory to anti-VEGF treatment (no improvement in BCVA or central macular thickness (CMT)). It is believed that factors such as mitochondrial structural and functional damage, due to oxidative stress, are partially responsible for this lack of improvement. Flavoprotein fluorescence (FPF) has been shown to be a sensitive marker of mitochondrial function and has been found to correlate with the degree of diabetic retinopathy. FPF may also provide additional information regarding therapeutic response of patients receiving anti-VEGF treatment for DME. Eight patients with DR and DME with clinically significant DME (CSDME) who underwent anti-VEGF (bevacizumab) treatment were imaged before injection and at follow-up visit using FPF in addition to standard color fundus photography and OCT CMT. A strong correlation r = 0.98 (p = 0.000015) between the FPF decrease and the BCVA improvement was observed; BCVA improved as FPF values decreased. Notably, in the same patients, the correlation between OCT CMT decrease and BCVA improvement (r = 0.688) was not found to be significant (p = 0.13). These findings suggest that FPF can detect improvement in metabolic function preceding structural improvement and even with small changes in edema. Additionally, FPF may be supplementary to current diagnostic methods for earlier detection of therapeutic response to anti-VEGF treatment in patients with DME.

Effect of Spectral Domain Optical Coherence Tomography Image Quality on Macular Thickness Measurements and Error Rate

ABSTRACTPurpose: To evaluate the effect of Topcon spectral domain optical coherence tomography (OCT) image quality on macular thickness measurements and the error rate in healthy subjects and patients with clinically significant diabetic macular edema (CSME).Methods: In this prospective, comparative case series, macular thickness measurements, and the rate of decentration and segmentation errors were evaluated before and after reducing the image quality factor (QF). The measurements were evaluated again after correcting the decentration and segmentation errors. To reduce the image QF below 45, tetracycline eye ointment was applied on the corneal surface.Results: Forty eyes of 40 subjects including 18 healthy eyes and 22 eyes with CSME were included. In both groups, the difference in central subfield thickness measurements before and after reducing the image QF was not statistically significant both before and after error correction (all P>0.05). The rate of decentration error was statistically similar before and after reducing image QF in normal and CSME eyes (P=0.50, P=0.69, respectively). However, the rate of segmentation error was statistically significantly higher after reducing image QF both in normal and CSME eyes (P=0.008 and P=0.004, respectively). In both groups, eyes with a segmentation error had higher image QF reduction (both P=0.01).Conclusion: Reducing image quality results in a higher rate of the segmentation error in normal eyes and in eyes with CSME.

Effects of focal/grid laser treatment on the central visual field in diabetic macular oedema: a 2-year follow-up study.

PurposeTo assess the long‐term effects of focal/grid laser treatment on the central visual field in subjects with clinically significant diabetic macular oedema (CSMO).MethodsTwenty‐six subjects with CSMO were included in the study. Fundus photography, assessment of retinal thickness by time‐domain optical coherence tomography (OCT), measurement of visual acuity (VA) and standard automated perimetry of the central 10° of the visual field were performed at baseline before focal/grid laser treatment and thereafter at four follow‐up visits 6 months apart, when the laser treatment was also repeated in subjects with persistent oedema. Changes in VA and retinal thickness between baseline and study end at 24‐month follow‐up were calculated. Trends in changes in the visual field were assessed by linear regression of number of significantly depressed test points over time.ResultsOn average after the laser treatment, retinal thickness decreased by 17% and VA decreased by three letters. In most eyes, visual fields were stable over time: the mean of the trend slopes (0.05 points/month) did not differ significantly from 0 (p = 0.63). The number of depressed test points at follow‐up was not correlated with either the total number of laser effects or the number of laser sessions.ConclusionFocal/grid laser treatment for CSMO did not affect retinal sensitivity in the central visual field in the subjects included in this 2‐year follow‐up study.

The relationship between central retinal thickness relative change and visual prognosis in diabetic macular edema patients following intravitreal injection of ranibizumab

Background The studies on intravitreal ranibizumab for diabetic macular edema (DME) primarily focuses on the absolute change of central retinal thickness, while the affection of the relative change of central retinal thickness (RCRT) or relative change of central retinal thickening (RCRTing) on visual prognosis has not been elucidated completely. Objective This study aimed to evaluate the effect of RCRT and RCRTing in assessing visual prognosis in DME patients following intravitreal injection of ranibizumab. Methods A self-controlled observational study was designed.Thirty eyes of thirty patients with clinically significant DME (CSDME) were recruited in Beijing 401 Hospital of China Nuclear Industry from November 2013 to October 2014.Ranibizumab of 0.05 ml (10 mg/ml) was intravitreally injected by 30G syringe needle at 3.5 mm posterior corneal limbus.Best corrected visual acuity (BCVA) far 2.5 meters away modified ETDRs visual chart was examined before injection and 3 and 6 months after injection, and the BCVA difference value between before injection and 6 months after injection was calculated as the absolusion BCVA (ABCVA). Spectral domian optical coherence tomography (SD-OCT) system was employed to measure the central retinal thickness (CRT) and to calculate the RCRT and RCRTing value.The correlations of RCRT or RCRTing with ABCVA was analyzed. Results The LogMAR values were (0.66±0.20), (0.40±0.25)BCVA and (0.37±0.25) before injection and 3, 6 months after injection respectively in the CSDME patients, with a significant difference among them (F=36.79, P<0.05). The values were obviously improved 3 and 6 months after injection compared with before injection (both at P<0.05). The mean ABCVA (LogMar) of the patients was (0.30±0.21). The CRT 3, 6 , pmyjd sgyrt omkrvyopm values were (508.63±130.44), (331.07±71.84) and (311.77±64.47)μm before injection and respectively in the CSDME patients, showing a significant difference among them (F=49.78, P<0.05). The CRT values were evidently reduced 3 and 6 months after injection in comparison with before injection (both at P<0.05), and the mean ACRT value was (196.87±140.59)μm.The ABCVA values were (0.13±0.13), (0.44±0.14), (0.07±0.09) and (0.41±0.15)LogMAR in the RCRT<35% group, RCRT≥35% group, RCRTing<69% group and RCRTing≥69% group, respectively.Significant differences were found in ABCVA between the RCRT<35% group and RCRT≥35% group (t=-6.27, -8.65, both at P<0.05). RCRT and RCRTing showed the positive correlations with ABCVA in the CSDME patients (r=0.86, 0.79, P<0.05). Conclusions RCRT and RCRTing can identify well the optimal responders to intravitreal ranibizumab and predict BCVA improvement after treatment.RCRT has better association with ABCVA than RCRTing.RCRTing may be preferable when retinal thickening is more severe. Key words: Diabetes retinopathy/drug therapy; Macular edema/therapy; Central retinal thickness; Vision; Antibodies, monoclonal, humanized; Tomography, optical coherence; Vitreous body

Peripapillary nerve fiber layer thickness changes after macular photocoagulation for clinically significant diabetic macular edema

PurposeTo evaluate the effect of macular photocoagulation (MPC) on peripapillary nerve fiber layer (PNFL) thickness measurement in patients with clinically significant diabetic macular edema (CSME). MethodsThis study was a prospective interventional case series. Patients with CSME underwent MPC. Optical coherence tomography (OCT) was used to measure the PNFL and central macular thicknesses before and 3months after MPC. ResultsThirty-three eyes of 25 patients with a mean age of 59.4±7.2years were included. There was no statistically significant difference between pre- and post-MPC mean best corrected visual acuity (0.35±0.29 and 0.40±0.23 LogMAR, respectively, P=0.2). Mean baseline and 3months central macular subfield thickness was 305.9±90.7 and 317.5±112.4 microns, respectively (P=0.1). Peripapillary nerve fiber layer thickness was 105.7±10.0 before and 106.1±9.9 three months after MPC (P=0.7). No significant differences were found between pre and post MPC measurements in temporal, nasal, inferior and superior nerve fiber layer thickness in each quadrant around optic nerve head (P>0.05). ConclusionsMacular photocoagulation has no statistically significant effect on PNFL thickness measurements in patients with CSME.

SAVE: a grading protocol for clinically significant diabetic macular oedema based on optical coherence tomography and fluorescein angiography

AimTo analyse a new grading protocol for clinically significant diabetic macular oedema (CSME) based on spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA).Methods56 eyes of 40 patients with...

Subthreshold diode-laser micropulse photocoagulation as a primary and secondary line of treatment in management of diabetic macular edema.

BackgroundThe purpose of this study was to evaluate subthreshold diode-laser micropulse (SDM) photocoagulation as a primary and secondary line of treatment for clinically significant diabetic macular edema (CSDME).MethodsIn this prospective nonrandomized case series, 220 cases of nonischemic CSDME were managed primarily and secondarily by SDM photocoagulation on a 15% duty cycle with a mean power of 828 mW and a spot size of 75–125 μm. SDM treatment was repeated at 3–4-month intervals if residual leakage was observed. Additional intravitreal pharmacologic therapy was used according to the response. Follow-up varied from 12 to 19 (mean 14±2.8) months. Novel software designed by the authors was used to record the subvisible threshold laser applications and their parameters on the fundus image of the eye. Evaluation of the results of treatment was done using fluorescein angiography and optical coherence tomography (OCT). Primary outcome measures included changes in visual acuity and foveal thickness at OCT. Secondary outcome measures included visual loss of one or more Snellen lines and laser scars detectable on fundus biomicroscopy or fluorescein angiography.ResultsIn the primary treatment group, there was significant improvement or stabilization of visual acuity after the first 3–4 months, which was stable thereafter. Visual acuity was stable in the secondary treatment group. A corresponding reduction of macular thickness on OCT was noted during the follow-up period in both groups. Additional therapy included repeat SDM photocoagulation, intravitreal injection of triamcinolone, and pars plana vitrectomy. Laser marks seen as changes in retinal pigment epithelium on fundus biomicroscopy and fluorescein angiography were noted in 3.3% and 5.7% of cases. Our novel software could accurately record the location of all SDM-invisible applications.ConclusionMicropulse laser is an effective minimal intensity therapy that offers the clear advantage of minimizing or avoiding laser-induced visible retinal burn/scarring while reducing the foveal thickness in the management of selected cases of CSDME. Future prospective studies should include the use of SDM photocoagulation as a combined minimally invasive therapy to consolidate the prompt but temporary effects of anti-vascular endothelial growth factor or anti-inflammatory agents. Virtual localization of SDM-invisible applications using our proprietary software could be used to guide further retreatments.

Cost-Effectiveness of Various Interventions for Newly Diagnosed Diabetic Macular Edema

Anti-vascular endothelial growth factor therapies have revolutionized the treatment of clinically significant diabetic macular edema (CSDME); yet these agents are expensive, and whether they are cost-effective is unclear. The purpose of this study is to determine the most cost-effective treatment option for patients with newly diagnosed CSDME: focal laser photocoagulation alone (L), focal laser plus intravitreal ranibizumab (L+R), focal laser plus intravitreal bevacizumab (L+B), or focal laser plus intravitreal triamcinolone (L+T) injections. Cost-effectiveness analysis. Hypothetical cohort of 57-year-old patients with newly diagnosed CSDME. By using a Markov model with a 25-year time horizon, we compared the incremental cost-effectiveness of treating patients with newly diagnosed CSDME using L, L+R, L+B, or L+T. Data came from the DRCRnet randomized controlled trial, the Medicare fee schedule, and the medical literature. Costs, quality-adjusted life years (QALYs), and incremental costs per QALY gained. Compared with L, the incremental cost-effectiveness of L+R and L+B was $89903/QALY and $11138/QALY, respectively. L+T was dominated by L. A probabilistic sensitivity analysis demonstrated that, at a willingness to pay (WTP) of $50000/QALY, L was approximately 70% likely to be the preferred therapy over L+R and L+T. However, at a WTP of $100000/QALY, more than 90% of the time, L+R therapy was the preferred therapy compared with L and L+T. In the probabilistic sensitivity analysis, L+B was found to be the preferred therapy over L and L+T for any WTP value >$10000/QALY. Sensitivity analyses revealed that the annual risk of cerebrovascular accident would have to be at least 1.5% higher with L+B than with L+R for L+R to be the preferred treatment. In another sensitivity analysis, if patients require <8 injections per year over the remainder of the 25-year time horizon, L+B would cost <$100000/QALY, whereas L+R would be cost-effective at a WTP of $100000/QALY if patients require fewer than 0.45 injections per year after year 2. With bevacizumab and ranibizumab assumed to have equivalent effectiveness and similar safety profiles when used in the management of CSDME, bevacizumab therapy confers the greatest value among the different treatment options for CSDME. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Complications of intravitreal triamcinolone acetonide for macular edema and predictive factors for intraocular pressure elevation.

To investigate the complications of intravitreal triamcinolone acetonide (IVTA) for the treatment of macular edema, and to determine the risk factors for intraocular pressure (IOP) elevation. Charts of patients with macular edema secondary to branch retinal vein occlusion (BRVO), diabetic retinopathy and uveitis who had received IVTA injections were reviewed to document its complications. IOP elevation was defined as a pressure of ≥24mmHg at some point during follow-up. Multivariate logistic regression analysis was performed to characterize baseline risk factors for this elevation. The study included 111 eyes of 65 female and 46 male patients with a mean follow-up of (11.6±5.1) months. Of the 111 eyes, 52 (46.8%) had macular edema secondary to BRVO, 44 (39.6%) had clinically significant diabetic macular edema (CSDME) and 15 (13.5%) had non-infectious uveitis with macular edema. IOP was recorded ≥ 24mmHg in 38 eyes (34.2%) during the follow-up. Higher baseline IOP (P=0.022), younger age (P=0.003), and male gender (P=0.014) were significant risk factors for IOP elevation after IVTA injection. Eyes with prior vitrectomy were less likely to have IOP elevation (P=0.054). Two eyes (5.2% of eyes with increased IOP) underwent trabeculectomy, and 9 eyes (16.3% of the phakic eyes) necessitated cataract surgery. Other complications included branch vein occlusion (1.8%), sterile endophthalmitis (0.9%) and pseudohypopyon (0.9%). IVTA has side effects with IOP elevation and cataract formation being the two most common. A subset of patients is more prone to developing increased IOP following IVTA, namely, younger male patients with higher baseline IOP.

Quantification of external limiting membrane disruption caused by diabetic macular edema from SD-OCT.

Disruption of external limiting membrane (ELM) integrity on spectral-domain optical coherence tomography (SD-OCT) is associated with lower visual acuity outcomes in patients suffering from diabetic macular edema (DME). However, no automated methods to detect ELM and/or determine its integrity from SD-OCT exist. Sixteen subjects diagnosed with clinically significant DME (CSME) were included and underwent macula-centered SD-OCT (512 × 19 × 496 voxels). Sixteen subjects without retinal thickening and normal acuity were also scanned (200 × 200 × 1024 voxels). Automated quantification of ELM disruption was achieved as follows. First, 11 surfaces were automatically segmented using our standard 3-D graph-search approach, and the subvolume between surface 6 and 11 containing the ELM region was flattened based on the segmented retinal pigment epithelium (RPE) layer. A second, edge-based graph-search surface-detection method segmented the ELM region in close proximity "above" the RPE, and each ELM A-scan was classified as disrupted or nondisrupted based on six texture features in the vicinity of the ELM surface. The vessel silhouettes were considered in the disruption classification process to avoid false detections of ELM disruption. In subjects with CSME, large areas of disrupted ELM were present. In normal subjects, ELM was largely intact. The mean and 95% confidence interval (CI) of the detected disruption area volume for normal and CSME subjects were mean(normal) = 0.00087 mm(3) and CI(normal) = (0.00074, 0.00100), and mean(CSME) = 0.00461 mm(3) and CI(CSME) = (0.00347, 0.00576) mm(3), respectively. In this preliminary study, we were able to show that automated quantification of ELM disruption is feasible and can differentiate continuous ELM in normal subjects from disrupted ELM in subjects with CSME. We have started determining the relationships of quantitative ELM disruption markers to visual outcome in patients undergoing treatment for CSME.

Sequential posterior subtenon injection of triamcinolone acetonide with macular grid/focal photocoagulation for clinically significant diabetic macular edema

PurposeTo evaluate the efficacy of sequential posterior subtenon triamcinolone acetonide (PSTA) injection with macular grid/focal laser photocoagulation for clinically significant diabetic macular edema (CSME). MethodsProspective, interventional clinical trial. Between July 2007 and March 2008, 41 eyes of 32 patients (17 males and 15 females) with Type II diabetes mellitus and diffuse clinically significant macular edema according to the Early Treatment Diabetic Retinopathy Study criteria were recruited. PSTA was used as the first line of treatment, followed by macular focal/grid photocoagulation 2 weeks later. In patients with persistent macular edema, a second dose of PSTA followed by additional focal laser treatment was administered 8–10 weeks later. ResultsBest-corrected visual acuity (BCVA) calculated as logarithm of the minimum angle of resolution (logMAR) unit showed significant improvement both after 3 weeks (0.79±0.27, p=0.001) and after 6 months (0.77±0.29, p=0.001) in comparison with the baseline values 0.92±0.24. Central macular thickness (CMT) was significantly reduced both after 3 weeks (336.2±125.8μm, p=0.001) and after 6 months (342.2±127.2μm, p=0.001) in comparison with the baseline values 437.1±186.5μm. Total macular volume (TMV) was also significantly reduced both after 3 weeks (10.2±1.8mm3, p<0.05) and after 6 months (10.3±2.0mm3, p<0.05) in comparison with the baseline values 11.9±2.1mm3. There were no significant differences in BCVA, CMT, and TMV between 3 weeks and 6 months posttreatment. ConclusionOne or two sessions of sequential PSTA injection and macular grid/focal photocoagulation may improve or stabilize visual acuity, CMT, and TMV for at least 6 months in patients with CSME.

A Prospective Randomized Trial of Intravitreal Bevacizumab or Laser Therapy in the Management of Diabetic Macular Edema (BOLT Study) : 12-Month Data: Report 2

To report the findings at 1 year of a study comparing repeated intravitreal bevacizumab (ivB) and modified Early Treatment of Diabetic Retinopathy Study (ETDRS) macular laser therapy (MLT) in patients with persistent clinically significant diabetic macular edema (CSME). Prospective, randomized, masked, single-center, 2-year, 2-arm clinical trial. A total of 80 eyes of 80 patients with center-involving CSME and at least 1 prior MLT. Subjects were randomized to either ivB (6 weekly; minimum of 3 injections and maximum of 9 injections in the first 12 months) or MLT (4 monthly; minimum of 1 treatment and maximum of 4 treatments in the first 12 months). The primary end point was the difference in ETDRS best-corrected visual acuity (BCVA) at 12 months between the bevacizumab and laser arms. The baseline mean ETDRS BCVA was 55.7+/-9.7 (range 34-69) in the bevacizumab group and 54.6+/-8.6 (range 36-68) in the laser arm. The mean ETDRS BCVA at 12 months was 61.3+/-10.4 (range 34-79) in the bevacizumab group and 50.0+/-16.6 (range 8-76) in the laser arm (P = 0.0006). Furthermore, the bevacizumab group gained a median of 8 ETDRS letters, whereas the laser group lost a median of 0.5 ETDRS letters (P = 0.0002). The odds of gaining > or =10 ETDRS letters over 12 months were 5.1 times greater in the bevacizumab group than in the laser group (adjusted odds ratio, 5.1; 95% confidence interval, 1.3-19.7; P = 0.019). At 12 months, central macular thickness decreased from 507+/-145 microm (range 281-900 microm) at baseline to 378+/-134 microm (range 167-699 microm) (P<0.001) in the ivB group, whereas it decreased to a lesser extent in the laser group, from 481+/-121 microm (range 279-844 microm) to 413+/-135 microm (range 170-708 microm) (P = 0.02). The median number of injections was 9 (interquartile range [IQR] 8-9) in the ivB group, and the median number of laser treatments was 3 (IQR 2-4) in the MLT group. The study provides evidence to support the use of bevacizumab in patients with center-involving CSME without advanced macular ischemia.

Prospective randomised controlled trial comparing sub-threshold micropulse diode laser photocoagulation and conventional green laser for clinically significant diabetic macular oedema

Aim:The study was a prospective randomised controlled double-masked trial performed in two centres to compare sub-threshold micropulse diode laser photocoagulation (MPDL) with conventional green laser photocoagulation (CGL) in the treatment...