Diabetic retinopathy occurs because the retinal vessels are abnormal, either because they proliferate (proliferative retinopathy) or because the vessels are func- tionally incompetent and leak ﬂ uid and lipid into the retina. Visual impairment occurs when edema affects the central retina or macula (diabeticmacularedema, or DME). Macularedema is reversible in the early stages but chronic edema may lead to irreversible changes in the retina. In a large cohort study, diabetics with macularedema had a 50% prevalence of visual impairment and a 20% prevalence of blind- ness, compared to 16% and 4% respectively in diabetic patients without macularedema. 5 Figures 1 and 2 contrast the ophthalmic features of macularedema with a
On comparing the results of the outcome measures for each pair of drugs, we found that there was a significant dif- ference in the maintained improvement in visual acuity and the decrease in the CMT at week 12 on using IVB alone or combined with IVT. While this significant difference was not observed with IVT alone, this confirms the better and maintained effect of IVB over IVT in the treatment of DME without additional benefit of combining IVT to IVB.
Photocoagulation was performed by the same surgeon (ISO) using an 810 nm diode-laser (OcuLight SLx; Iridex Corp, Mountain View, CA, USA) in the micro pulse emission mode. The laser power was adjusted to 1,000 mW with a duration of 300 msec and a 15% duty cycle. The spot size was set at 75–125 µ m and applied confluently to cover the whole area of macularedema up to 200 µ m from the cen- ter of the foveal avascular zone using an Ocular Mainster (standard) focal/grid lens (Ocular Instruments Inc, Bellevue, WA, USA). If a laser tissue reaction was noted, the power was reduced in steps of 200 mW until no reaction could be seen. The fundus picture was imported into specially designed pro- prietary software where an Amsler’s grid pattern was plotted on the macular area based on identifying the temporal edge of the optic nerve and the center of the foveal avascular zone (Figures 1 and 2). A color palette was used after each treatment session to mark the treated small squares corresponding to the treated zone with the performed laser parameters (Figures 2 and 3). The color palette could be changed and marked dif- ferently according to the laser parameters in each treatment session. The software could make the invisible laser spots identifiable on the Amsler’s grid square pattern. Laser param- eters and applications were also recorded for each treatment session. We considered one quadrant involved if more than 50% of the area was thickened with exudates or hemorrhages. Follow-up visits were performed at one month after treatment and every 3 months thereafter, and included fundus biomicros- copy, best-corrected visual acuity, fluorescein angiography, and OCT. Supplemental treatments were performed using the same protocol as for the primarytreatment and were considered at each follow-up visit in those eyes with treatable lesions on
The average thickness of the central 1 mm field of the 6 mm OCT-modified ETDRS grid was used to evaluate changes in the CRT over time. The presumed fovea was considered as the region with the photoreceptor layer alone and was checked again retrospectively using the device’s automatic follow-up tool. SFCT was measured using the horizontal scan of the star scan mode centered at the fovea. Scans were evaluated by the two scorers after marking the choroid-scleral border (1 scan × rater × follow-up period). SFCT was manually measured from the hyperreflective line of the Bruch’s membrane to the hyperreflective line of the choroid-scleral interface (Add- itional file 1: Figure S1) using the digital caliper tool in the Heidelberg Eye Explorer software. Whenever there were doubts about the choroid-scleral border, measure- ments were compared with the horizontal line scan bypassing the fovea of the macular cube scan. The integ- rity of the EZ was evaluated at baseline and after the loading dose, in the central 500 μm in either direction of the fovea (Fig. 1a and b). The EZ was considered dis- rupted when there was any focal absence of the second hyperreflective band in the central 1000 μm either in the horizontal or in the vertical line scans centered at the fovea of the star scan mode and that could not be attrib- uted to the shadowing effect of cysts or retinal vessels . Whenever the raters did not agree, the ellipsoid zone was considered unreadable. All scans were per- formed from 9.00 a.m. to 1.00 p.m.
recent onset disease. With regard to ocular complications, one needs to take into account that cataract surgery will become necessary in nearly all patients who are phakic at the initiation of treatment. An increase in intraocular pres- sure may occur, but surgical intervention becomes necessary only in a limited number of patients. Therefore, fluocinolone acetonide may represent an effective second-line treatment option for patients with chronic, refractory, diffuse DME, which to date comprise a group of patients with limited prospects for visual recovery (Figures 2 and 3). At present, as a first-line treatment, laser photocoagulation remains relevant for focal vasogenic DME not involving the fovea, and may help to maintain good visual acuity. Anti-VEGF treatment seems indicated in new focal DME involving the
Abstract: Diabeticmacularedema is the major cause of visual acuity impairment in diabetic patients. The exact etiopathogenesis is unknown and, currently, grid/focal retinal laser photocoagulation represents the recommended treatment. It has been demonstrated that vascular endothelial growth factor (VEGF) plays a key role in the pathogenesis of diabeticmacularedema by mediating vascular permeability and accumulation of intracellular and extracellular fluid, and thereby represents an appealing candidate as a therapeutic target for the treatment of diabeticmacularedema. The advent of intravitreal anti-VEGF drugs has opened up a new era for the management of diabeticmacularedema. At present, three anti-VEGF substances are available for routine clinical use, ie, pegaptanib, ranibizumab, and bevacizumab. The aim of this review is to summarize the evidence supporting the use of ranibizumab in clinical practice. Most of the studies analyzed in this review are prospective, controlled clinical trials that have focused on documenting the therapeutic effect of ranibizumab and its safety, providing encouraging results.
acuity. When the initial visual acuity loss was mild, there were no apparent differences, on average, among the study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. In the present study, the baseline visual acuity was between 0.25 and 0.1, which is a common presenting visual acuity in parts of the world without a tight diabetic retinopathy screening program. In those eyes, other studies 15,23 showed that aflibercept was
Diabeticmacularedema (DME), is one of the most common causes of visual impairment in the diabetic patients . The worldwide prevalence of diabetes is estimated to rise to 366 million by 2030 . The 10-year incidence of macularedema in patients with type 2 diabetes was up to 14%, and 29% of type 1 progressed into DME over a 25-year period [3,4]. Hence, finding a safe and effective treatment of DME becomes urgent. Despite the high prevalence of DME, there is no definite treatment because of its complicated pathophysiologic mechanism, which is still not fully understood. However, there is no single modality that has been shown to be superior. The Early TreatmentDiabetic Retinopathy Study (EDTRS) showed that macular laser photocoagulation (MPC) is effective in reducing the risk of visual loss by approximately 50% in eyes with clinically significant macularedema . However, unsatisfactory outcomes are frequent, and 12% treated eyes developed moderate visual loss. Moreover, about 15% patients fall into the category of refractory DME and do not respond to repeated laser treatments. This shows that in spite of laser being the gold standard treatment of DME, some patients do not respond to laser . Various modalities of treatment are currently being tried in the management of persistent; laser refractory DME such as supplemental laser, intravitreal steroid injection, and anti-vascular endothelial growth factor (anti-VEGF) injection .
The absolute number of DME treatments administered over the study period and the change in distribution of individual DME treatments (as a percentage of total DME treatments) are presented in Figure 1A and B, respectively. The low number of treatments in the earlier years (2009–2011) is likely a result of the study design, as patients were required to have received anti-DME treatment during the 2012–2013 period, but not necessarily before 2012. Between 2009 and 2014, there was an overall decline and increase in the use of laser and anti-VEGF agents, respectively, whereas the use of corticosteroids remained relatively constant. Most notably, the use of bevacizumab decreased in proportion with the increase in ranibizumab use. Only six cases of aflibercept use were recorded, which reflects the fact that aflibercept became commercially available only in the first half of 2014.
As there was no control group in the present study, it cannot conclusively be stated that the remission of dia- betic edema was in each case the effect of the therapy; there is a chance that it might have occurred in the natu- ral course of the disease. Moreover, the potential effects of glycemic levels or other systemic parameters that can influence the course of DME were not taken into account.
The analysis pursued is characterized by specific draw- backs and limitations. Since the analysis was undertaken from the perspective of Greek Health Care Insurance Fund, only direct medical costs for the treatment of VI due to DME were considered. Notwithstanding, it is acknowledged that the ramifications of a DME have a wider impact generating significant indirect costs (e.g. productivity losses) that could enhance the results of our analysis. A specific drawback regarding the adaptation of this cost-effectiveness model was the fact that, due to lack of Greek-specific studies, DME-related mortal- ity was assumed to be the same as in the UK core model. Another limitation of the study was the fact that it did not account for variation in treatment practice (i.e. the num- ber of injections in year 1–3 was tested). Moreover, the clinical inputs of the current study were extracted from a network meta-analysis and not a head to head study. Finally, within the context of customization, it should be noted that the results refer strictly to Greece and on the basis of the present time resource and drug prices. If any
Abstract: Macularedema is one of the leading causes of vision loss among patients with retinal vein occlusion, diabetic retinopathy, and posterior chamber inflammatory disease. However, the treatment of macularedema is considerably limited by the difficulty in delivering effective doses of therapeutic agents into the vitreous cavity. In recent years, the development of a sustained-release dexamethasone intravitreal implant (Ozurdex ® ) has enabled more controlled
spective, randomized clinical trial comparing vitrectomy to serial anti-VEGF injections is needed to determine the rela- tive efficacy and cost-effectiveness of these two treatments for CI-DME. Such an idea has been submitted to the DRCR network, which has the infrastructure enabling execution of such a trial. Relevant evidence for this protocol idea can be obtained from the International Consortium Investigating Early Vitrectomy in DiabeticMacularEdema Patients trial (clinical trials identifier #NCT02639507), a prospective, international, multicenter trial with standardized collection of VA and OCT data that is currently enrolling patients.
This study demonstrates that three months after the intra- vitreal injection of TA and the subtenon injection of TA there is a statistically significant improvement in visual acuity and an equally significant reduction in retinal thickness. Six months after IVT the patients presented a recurrence of macularedema with loss of visual acuity whereas six months after SBT injection retinal thickness and visual acuity remained stable. After one, three and six months we observed a statistically significant rise of the IOP in the eyes treated with IVT injection whereas in the SBT injection group, no statistically significant variations of the IOP were found. None of patients developed cata- ract or needed anti-glaucoma drugs during the follow-up. Macularedema is the main cause of loss of visual acuity in diabetic patients [13,14]. It may occur at any stage of the retinal disorder and is the most common cause of sight reductions in these subjects.
The SD-OCT images of macular retinal layers were investigated in all patients with high-resolution OCT (Optos OCT SLO, United Kingdom) and assessed after dilation of the pupil. In each retinal OCT, high-density horizontal raster scans were used. 6-mm raster scans of the axial retinal sections was performed, which simul- taneously acquired SD-OCT and near-infrared reflec- tance images. This enabled precise identification of corresponding sites of pathology between the different
side effects. The intravitreal 0.7 mg DEX implant gives ophthalmologists an alternative treatment strategy in DME to reduce the treatment burden and to increase the therapeutic efficacy, especially in pseudophakic eyes without the risk of glaucoma. It also helps those with persistent DME despite numerous anti-VEGF treatments, in patients with anti-VEGF contraindicated due to systemic concerns, and in combination therapies with laser and intravitreal anti-VEGF. In addition, head-to-head clinical trials between anti-VEGFs and the DEX implant will improve our knowledge of the efficacy and safety. The best treatment option in DME should be tailored to individual cases and should be defined according to the disease and patient characteristics.
was allowed at 24 months. Patients receiving ranibizumab consistently achieved superior gains in vision compared with those randomized to sham, a finding that applied to all subtypes of diabetic patients, and to those who were previously treated or treatment-naïve. Improvement of $15 letters in vision (the primary efficacy endpoint) in patients receiving sham injections, 0.3 mg ranibizumab, or 0.5 mg ranibizumab, was achieved by 18.1%, 44.8%, and 39.2% of patients in RISE, and 12.3%, 33.6%, and 33.3% of patients in RIDE. Mean best corrected visual acuity in ranibizumab-treated patients improved from + 10.9 to + 12.5 letters compared with + 2.3 and + 2.6 letters in the sham groups. Ranibizumab improved vision rapidly, with patients experiencing statistically significant changes of + 4 to + 5 letters by seven days after the first injection. Ranibizumab prevented the loss of $15 letters of vision in 96.1%–98.4% of patients, compared with 89.8%–91.5% in sham patients. As was seen in the age-related macular degeneration trials, patients with the worst baseline visual acuity experienced the largest gains. Resolution of macularedema on optical coherence tomography and cessation of leakage on fluorescein angiography were both more commonly seen in patients receiving ranibizumab. Average improvements in central retinal thickness of − 250.6 µ m to − 270.7 µ m for patients receiving ranibizumab compare favorably with − 125.8 µ m to − 133.4 µ m for sham- treated patients.
Results: A 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 TreatmentDiabetic Retinopathy Study) letters (range 4–21). Apart from a transient vitreous hemorrhage in one eye, there were no significant treatment-related complications.
Currently, surgeons have three intravitreal corticosteroid options for the treatment of DME: the dexamethasone deliv- ery system, the fluocinolone acetonide insert, and off-label intravitreal triamcinolone acetonide (Table 1). All three agents, as well as the larger fluocinolone acetonide surgical implant, are associated with risks of cataract progression and IOP elevation (Table 2). There is no current consensus regarding the indications for intravitreal corticosteroids, 67 but
One of the challenges with micropulse is the invisibility of laser applications, which makes it difficult to follow up the patients and re-treatment. NAVILAS® provides an additional advantage over other micropulse laser systems is that it provides the reports with treated area along with laser parameters. Application of confluent laser marks could be challenging using conventional slit lamp laser systems due to eye movement and the unavailability of eye tracking. NAVILAS® provides a computerized laser plan- ning and eye tracking during laser application which is accurate and beneficial for subthreshold laser as the laser spots are not visible. Two studies have shown that use of the NAVILAS® results in higher accuracy of targets for photocoagulation compared to the conventional method without the navigating system [29–31]. However, previous reports suggest subthreshold laser application in the “whole posterior pole” which doesn’t require the in- formation about the previously performed subthresh- old laser applications. [32, 33]