Click here to view the embedded video.

Click here to view the embedded video.

Advantages:

Intravitreal triamcinolone injections turned out to be effective in reducing macular edema and improving vision in refractory DME after a laser treatment or even as an initial treatment. The steroid-related adverse events, e.g. cataract and elevated intraocular pressure, should be weighed against the benefits of the treatment.

Methods:

Twenty-mg triamcinolone acetonide intravitreal injections (IVTA) were applied to 110 DME patients after ineffective laserphotocoagulation or as a initial treatment. BCVA for distant and near vision, central retinal thickness and intraocular pressure (IOP) were analyzed before and after the treatment at 1 week and 1, 3, 6 month intervals. The measurements were continued in cases of repeated IVTA.

Effectiveness / Safety:

We observed a statistically significant improvement in BCVA in near and distant vision and a decrease in central retinal thickness after all time-intervals after IVTA in the observed group. BCVA to distant vision was not statistically significantly better after repeated IVTA. IOP increase was observed at 1 week and 1,3 months after IVTA, but not at 6 months after IVTA. No sight-threatening side effects of IVTA were observed.

Take home message:

IVTA is useful in stabilizing DME progression, although its therapeutic effect can be time-limited.

Click here to view the embedded video.

Persistent diffuse macular edema (ME) or cystoid ME is a result of chronic inflammation with the generalized breakdown of the inner blood retinal barrier and fluid accumulation, primarily in the outer plexiform layer. This process is characterized by the development of hard exudates and progressively lost of vision.

Triamcinolone acetonide is the most effective anti-inflammatory agent. After injection into the vitreous cavity concentration of medicine considerably higher in compare with other methods of introductions, therapeutic effect more longer due to slowly dissolving in the vitreous up to three month. Intra vitreous using of triamcinolone has no systemic effect, which is very important in patients with diabetes – (2 minutes).

Intravitreal 4mg triamcinolone injection was done to 29 patients (33 eyes) with (ME). Injections performed by standard method. We used TA injection in cases of persistent diffuse macular edema (ME) with hard exudates. We did not take into consideration the thickness of retina, main indication was the presence of hard exudates on the big area in posterior pole of the eye at list 3 months or more. On of the advantages of TA is ability to stimulate the dissolving of hard exudates with the diminished of retinal thickness.

We did not repeat injection in short period of time. Next injection we did after 6 months (3 eyes – 3 injections, 6 eyes – 2 injections, in all cases interval between injections was 6 month).
After 3 months macular thickness diminished on all eyes from mean 552,5±96,3µm on 203,8±97,7µm (p<0,01 by Wilcoxon test), best-corrected visual acuity improved on 26 eyes (78,8%), on 7 eyes remained the same. During next 12 months on 9 (27,3%) eyes macular edema recurred, and intravitreal 4mg triamcinolone injection repeated (Will be present OCT) – (2 minutes).
Whole period of observation is 3 years. During this period stable ME resolution was on 12 eyes (36,4%), ME stabilization on 13 eyes (39,4%), ME progression – 8 eyes (24,2%). Сomplications: 1 eye – pseudohypopion (3%), cataract progression – 10 eyes (30,3%), on 2 eyes (6,0%) cataract surgery was performed in a period of 1 year after first injection, 5 eyes (15%) temporary ocular pressure increasing. There were not any cases with glaucoma progression. Progression of cataract decreased visual acuity.  Best-corrected visual acuity in a period of 3 years worsened from baseline on 6 eyes (18,2%), stable increased on 19 eyes (57,6%) and on the 8 eyes (24,2%) did not changed.
In this presentation we presented only cases with TA injections without combination with laser treatment
Main cause of failure of any treatment of diabetic patients is inadequate systemic control of diabetes also it takes place in cases of TA injections. Of course, diffuse failure of foveal capillaries plays an important role in a recurrent of edema, especially after all TA crystals dissolved in vitreous cavity. We did not do TA injections in cases of retinal ischemia, excluded them after fluorescent angiography investigation. TA injection influence on the development of ischemia but less than avastin or lucentis. All these reasons together decrease the efficacy of TA treatment of macular edema.

Click here to view the embedded video.

Advantages:

Use of intravitreal injection of crystalline corticosteroids- bethamethasone and triamcinole dose of 4 mg in 0.1 ml allows to improve visual acuity and restore adequate morphological retinal thickness in patients with diffuse diabetic macular edema.

Methods:

Comparison of efficacy and safety of intravitreal injection of 4 mg (0.1 mL) triamcinolon (36 patients – 40 eyes) and 4 mg (0.1 mL) bethamethasone (60 patients – 69 eyes) in treatment of diffuse diabetic macular edema.

Effectiveness / Safety:

Betamethasone was associated with a significantly higher improved in visual acuity, with maintained improvement over 6-12 months, and in reduction of foveal thickness when compared to TA. Both are identical regarding onset of action in reducing macular thickness.

After 3 months of intravitreal bethamethasone injection, the retinal thickness was 10% lower, after 6 months it was 17% less, and in 12 months it was 24% lower than the intravitreal injection of triamcinolon. When compared to TA, intravitreal betamethasone injection was associated with an early initial rise in IOP (please specify in % of patients) during first month after injection while TA may increase IOP in % of patients at any stage following injection.

Take home message:

Intravitreal use of bethamethason is safe and more effective in comparison with triamcinolone.

Click here to view the embedded video.

Advantages:

Given the chronic nature of diabetic macular edema (DME), an implant (ILUVIEN^®) that releases a continuous, submicrogram daily dose of fluocinolone acetonide (FAc) could fill an unmet need for continuous long-term therapy.

Methods:

The Fluocinolone Acetonide in Diabetic Macular Edema (FAME) study consisted of 2 randomized, prospective, multicenter, double-masked, sham-controlled, parallel-group phase 3 trials enrolling patients whose DME was uncontrolled despite receiving at least 1 prior macular laser treatment. Patients (N=956) were randomized to receive 0.2 μg/d FAc (n=376), 0.5 μg/d FAc (n=395), or sham (n=185). After 6 weeks, all patients were eligible for rescue laser at the discretion of the masked investigator; after 12 months, all were eligible for retreatment with randomized study treatment if they met predetermined criteria. Primary endpoint was the proportion of patients gaining ≥15 letters of best-corrected visual acuity (BCVA) at month 24. Total study duration was 36 months. Baseline DME duration (prespecified) was analyzed to determine if patients with chronic DME experienced an improved risk/benefit profile.

Effectiveness / Safety:

28.7% of 0.2 μg/d FAc–treated patients experienced a ≥15-letter BCVA improvement at month 24 vs 16.2% of sham-treated controls (P=0.002); results were maintained at month 36 (28.7% vs 18.9%, P=0.018). Of patients with chronic DME (DME ≥3 years at baseline), 34.0% receiving 0.2 μg/d FAc experienced a ≥15-letter BCVA improvement vs 13.4% of controls at month 36 (P<0.001).

By 36 months, cataract surgery was performed in 80.0% of phakic patients receiving 0.2 µg/d FAc (85.1% of chronic patients) and 27.3% of phakic controls; 4.8% of patients in the 0.2-µg/d group (5.3% of chronic patients) required intraocular pressure (IOP)-lowering surgery vs 0.5% of controls.

Take home message:

FAc implants improved BCVA over 36 months; a low rate of incisional procedures for elevated IOP was observed. Benefits were most pronounced in chronic DME patients.

Purpose:

To investigate micropulse contiguous grid laser (MCGL) for DDME involving the fovea, and to correlate OCT findings with resolution target visual fields (RTVF) scotomas and global macular acuity (GMA).

Methods:

One year retrospective review of sequentially treated eyes including, OCT, FA, RTVF and NEI-VFQ 25.

Results: In 56 eyes GMA improved 0.2 logMAR in 34%, with none worsening >0.3 logMAR. Central OCT decreased 173 µm+9.3. The VFQ improved significantly in 28%. RTVF scotoma density was associated only with disruption of IS/OS and ELM with ONL thinning.

Effectiveness / Safety:

MCGL stabilized edema with central vision improvement in 1/3 without laser scotomata. Intact IS/OS, ELM and no ONL thinning were associated with less RTVF defects and better prognosis.

Take home message:

Initiate treatment for DDME with micro pulse contiguous grid laser.

Advantages:

Combined treatment of diffuse diabetic macular edema using intravitreal injection of bethamethasone and laser coagulation is effective in improving visual acuity and restoration of the morphofunctional state of the retina.

Methods:

Intravitreal injection 4 mg (0.1 ml) of bethamethasone combined with laser coagulation was conducted in 33 patients (33 eyes) with diffused diabetic macular edema. Patients were divided into 2 subgroups: 16 patients received steroid therapy after laser coagulation (in case of refractory macular edema insensitive to laser coagulation) and 17 before laser therapy (with diffuse and complicated macular edemas).

Effectiveness / Safety:

Both options of combination therapy are equally effective in improving visual acuity. However, in treatments where bethamethasone was injected prior to laser coagulation, duration of increase of maximum corrected visual acuity is greater: over 18 months visual acuity is 136% higher than in patients who received bethamethasone injections after laser coagulation.  Effect of reducing thickness of retina is more pronounced in case of endovitreal bethamethasone injection before laser coagulation: after 1 month – by 31%, after 3 months – by 45%, after 6 months – by 47%, after 12 months by 44%, after 18 months by 46% Recurrence of macular edema is possible at any stage of observation with following conditions: unstable glycemia and blood pressure, progressive nephropathy, presence of vitreotractions, unclosed by laser coagulation leaking etc.  If conducting intergroup comparison on the predisposition to recurrence, the rate of recidivism is higher in the group with administration of steroid therapy after laser coagulation (21.3%) compared to 8% in the group where steroids were injected before laser coagulation, during 18 months of observation.

Take home message:

Combined treatment when use of steroids precedes use of laser coagulation makes it possible to achieve longer clinical effect on stabilization of visual acuity and retinal thickness normalization within 18 months.

Advantages:

Intravitreal bevacizumab followed by laser micropulse in CSME offers a clear advantage of non-inducing a visible retinal burn and having a potential efficiency in reducing foveal thickness and visual acuity

Methods:

Prospective case series. One hundred and twenty cases of non-ischemic non-tractional CSME with macular thickness more than 400 microns as defined by OCT were managed by initial intravitreal bevacizumab injection of 1.25mg/0.1ml followed by laser micropulse using diode laser photocoagulation 3-4 weeks later at 15 % duty cycle with 1000 mW power and spot size of 75-125 microns. Laser micropulse is repeated in 3-4 months if residual leakage is observed. Follow up was maintained to 12 months. Our novel software labeling fundus imaging against areas of treatment designed by the author was used. Evaluation of treatment result was done using fluorescein angiography and OCT.

Effectiveness / Safety:

Bevacizumab was associated with decrease in central macular thickness from (447+/- 98 microns) to (326 +/- 53 microns) at 3-4 weeks follow up. Micropulse laser photocoagulation resulted in further improving central macular thickness at 3, 6 and 12 months to (268+/- 48 microns) in 77 cases (64 %). There were no associated retinal burn seen ophthalmoscopically, and only in few cases (8 cases), there was an association with fluorescein angiographic RPE window defect. Additional micropulse laser, repeated bevacizumab injection and vitrectomy was necessary in 36% of cases. Vision improved in 64 cases (53% of cases).

Take home message:

Initial intravitreal bevacizumab followed by micropulse laser is a useful minimal intensity effective therapy in management of selected cases of diffuse CSME.

Advantages:

Laser stimulation seems to be effective, safer, non-tissue harmful and cost effective to treat diabetic macular edema.

Methods:

Eighty-eight eyes of 78 diabetic patients with DME were treated with yellow diode laser (577 nm) suited for micropulse treatment in macular area. ETDRS best corrected visual acuity, High definition optical coherence tomography to determine central macular thickness, Fluorescein angiography (FA) and Mean central retinal sensitivity measured through microperimetry were performed at basal, 1,3,6 and 9 months after a single treatment.

Effectiveness / Safety:

Central macular thickness decreased by 180 µm at 12 months with an increase in visual acuity of 14 ETDRS letters and macular sensitivity improved. Laser lesions were not observed neither clinically nor on FA examination.

Take home message:

Use of micropulsed macular photo stimulation may be a selective alternative to stop progress and improve vision in DME with minimal or null thermal damage to the retina.

Click here to view the embedded video.

Advantages:

Aflibercept (VEGF Trap Eye, Eylea) has a longer duration of action compared to ranibizumab (Lucentis).

Methods:

Randomized clinical trials.

Effectiveness / Safety:

In a phase II trial patients with diabetic macular edema gained 9.7 letters with aflibercept every 8 weeks and 13.1 letters with aflibercept every 4 weeks.  Phase III trials, VISTA and VIVID, are underway.

Take home message:

Aflibercept may be an effective treatment for diabetic macular edema.

Click here to view the embedded video.

Advantages:

Intravitreal ranibizumab improves vision of patients with diabetic macular edema.

Methods:

Review of recent clinical trials such as DRCR.net.

Effectiveness / Safety:

DRCR trials showed that in patients with diabetic macular edema, intravitreal ranibizumab with prompt or deferred focal/grid laser had superior Visual Acuity outcome compared with focal/grid laser treatment alone.

Take home message:

Intravitreal ranibizumab is an effective treatment for diabetic macular edema.

Click here to view the embedded video.

Background:

Diabetic macular edema (DME) is a frequent complication of diabetic retinopathy. It is characterized to increased vascular permeability, due to blood-retinal barriers breakdown. Since macular laser treatment has shown poor efficacy to diffuse edema, surgical option of therapy is discussed. Several studies have proven the efficacy of pars plana vitrectomy (PPV) with inner limiting membrane (ILM) peeling in case of DME with a tractional component. Less is known in case of DME without tractional component.

Purpose:

To evaluate long-term anatomic and functional outcomes of PPV and ILM peeling in eyes with clinically significant diabetic macular edema (CSME).

Methods:

Retrospective, observational study based on the data of 74 eyes of 52 consecutive patients with CSME that underwent PPV and ILM peeling, performed by the same surgeon (G.P.). Inclusion criteria were one of the following: presence of vitreoretinal interface abnormalities on optical coherence tomography (OCT), large hard exudates involving or threatening the foveal centre, macular thickness exceeding 450 microns, unresponsive to other treatments CSME. Eyes were divided into two groups, with and without vitreoretinal interface abnormalities (namely group A and group B). Visual acuity (BCVA) and OCT were performed at baseline and postoperatively during follow up. Foveal thickness (FT) and total macular volume (TMV) were considered. Follow up ranged from 12 to 48 months (30 ±18).

Results:

BCVA significantly increased in both groups twelve months after treatment  (P=0.0001). Two years follow-up data were available for 45 of 74 eyes (60.8%): BCVA remained stable in 40 eyes (88.9%; 21 eyes in group A, 19 eyes in group B), and worsened in 5 eyes (11.1%; 3 eyes in group A, 2 eyes in group B). Three years follow-up data were available for 33 of 74 eyes (44.6%): BCVA remained stable in 26 eyes (78.8%; 16 eyes in group A, 10 eyes in group B), and worsened in 6 eyes (18.2%; 4 eyes in group A, 2 eyes in group B). OCT evaluations showed a significant reduction after 12 months and was maintained for the entire follow up, except for 3 eyes (4%) that worsened significantly after 24 months, and needed additional treatments (macular grid in 2 cases, intravitreal triamcinolone in 1 case). No significant differences were also observed when TMV was considered. Moreover, eyes with a higher FT were more likely to worsen during follow-up over the eyes with a lower FT, both in group A and B.

Conclusions:

In selected patients PPV with ILM peeling could lead to significant reduction of CSME and improvement of BCVA, regardless the presence of vitreoretinal abnormalities on OCT. In addition, FT reduction and visual improvement might persist up to 36 months.