Ординатура / Офтальмология / Английские материалы / Retinal and Vitreoretinal Diseases and Surgery_Boyd, Cortez, Sabates_2010
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Classification and Management of Diabetic Retinopathy
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Figure 11: Diffuse DME. No significant lipid exudation. Diffuse thickening of the retina and subfoveal retinal detachment. Leakage of fluorescein in late phases of the angiogram.
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Figure 12: Cystoid diabetic macular edema.
Many authors have claimed that diffuse DME has a poorer prognosis and is refractory to laser photocoagulation in many cases, but the evidence to support these claims does not arise from prospective clinical trials. Grid pattern laser photocoagulation may be helpful in some patients, but we believe that applying laser to markedly thickened retina is difficult and hazardous, because the anatomic landmarks are lost and because a
higher power of the laser will be induced to obtain a visible burn.
If edema is greater than 390 μm, intravitreal triamcinolone or intravitreal anti VEGF therapy to help reduce edema prior to laser application holds theoretical benefit.(9) If after one trial of laser, there is not significant improvement, a trial of intravitreal therapy may help, reducing macular edema for a more precise grid therapy.
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Figure 13: Diffuse macular edema. Increased macular thickness involving all quadrants.
LASER Treatment of DME
The burns should be placed 500-3000 μm from center of the macula in the first treatment. If retreatment is needed, burns could be placed 300-500 μm from center of macula.
The laser should darken or whiten the microaneurysm. For the grid treatment, mild, light burns of 100-200 μm are recommended, spaced one burn apart, 500 μm away from the center of the macula.
In eyes with severe non proliferative DR or early proliferative DR, the best strategy
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is immediate focal photocoagulation with delayed scatter panretinal photocoagulation.
The Diabetic Retinopathy Clinical Research Network reported the two year results of a multicenterrandomizedclinicaltrialcomparing intravitreal Triamcinolone and focal/grid laser for DME.(10) The mean visual acuity at 2 years was better in the laser group, even though the short term visual results were better in the Triamcinolone injected eyes. However, half of the eyes in the photocoagulation group still had central retinal thickening at 2-years and approximately 20% of laser treated eyes worsened 10 letters or more from baseline.
The authors recognize that it is a role for better treatments in the future and combination treatments are currently being evaluated.
Pharmacologic Treatment of
DME and Combination
Treatments
Intravitreal corticosteroids and antiangiogenic agents have been used in treatment of DME. Many studies demonstrated significant anatomic and functional improvements following the intravitreal therapy. There are three major problems with this treatment modality:
1.They do not work in all cases.
2.The visual benefit is short lived and repeated injections are needed.
3.Intravitreal corticosteroids have substantial adverse effects.
Corticosteroids. Corticoids are potent antiangiogenic and antiinflammatory agents. A number of papers demonstrated significant visual improvement after repeated intravitreal injections of triamcinolone. Significant intraocular pressure elevation occurs in about 50% of patients and a high proportion of patients required cataract surgery.(11)
The ideal dose of triamcinolone is not known. 4 mg is the most commonly used dose; higher doses (8 mg or more) may prolong the duration for the beneficial effect, but at adverse effects may be higher.
A single injection of 4 mg of triamcinolone usually causes an effective, but transitory reduction of macular edema, with maximum effect around 4 weeks, but the benefit is almost gone at 6 months (Figure 14).
Intravitreal corticosteroid implants have been developed, designed to release steroids into the vitreous for extended periods of time. Fluocinolone (Retisert, Bausch and Lomb) and dexametasone (Posurdex, Allergan) devices are undergoing clinical trials. Even though significant improvements in visual acuity have been reported, the side effects are significant (glaucoma and cataract surgery needed in a high proportion of cases) and limit widespread use in DME.
Anti-VEGF agents. Multiple studies have demonstrated that Pegnatib, Bevacizumab and
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a |
b |
c
Figure 14: 54 year-old diabetic woman. Cystoid diffuse macular edema. a) baseline. b) one month after intravitreal Kenalog, 4 mg. c). 10 months after the injection.
Ranibizumab appear to be effective in improving vision and reducing macular thickness in the short term in primary treatment for DME or in refractory cases. Arevalo et al. have reported thatprimary intravitrealBevacizumab for diffuse macular edema seems to provide stability or improvement of visual acuity at 24 months. The mean number of injections per eye was 5.0. However, 37 of 139 patients showed no change in visual acuity and 12 patients lost vision.(12)
Combination therapy. The main limitation of intravitreal pharmacologic therapy is the high recurrence rate of macular edema.
Repeated injections carry risks of complications and decreased efficacy. Kang et al (13) in randomized clinical demonstrated better visual and anatomic results with triamcinolone followed by macula grid laser compared with the triamcinolone only group. Lam study, suggested laser may prolong the effect of intravitreal triamcinolone(14).
Several studies comparing combined therapy with laser are now being conducted. At this time, there is not solid scientific evidence to state that laser, performed at 3 weeks of the intravitreal injection, may prolong the effect of intravitreal agents.
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A suggested algorithm for treatment of DME without vitreous traction.
1.Optimization of medical treatment.
2.Laser. Direct laser for leaking microaneurysm and grid treatment for areas of edematous retina with no defined focal leakage.
3.If there is a diffuse leakage with central thickness of 400 μm or more we prefer to reduce retinal thickness with intravitreal therapy. We would start with an intravitreal Avastin injection, because of its fewer side effects. If no effect,
we would repeat the injection after one month. If there is no change in retinal thickness, we would proceed with a tramcinolone (Kenalog) 4 mg injection (Figures 15 and 16).
Corticosteroids are more potent agents for DME, given their anti inflammatory capacity, in addition to their antiangiogenic effect.
4.Once a reduction in thickness is obtained, usually 3 weeks after the injection, laser, focal and grid is performed, under the guidance of a fresh angiogram.
a |
b |
c |
d
Figure |
15: |
53 year-old woman, diabetes 2 of 21 years duration, HbA1c 6.8%. Diffuse DME. a) pre Avastin. |
b) one |
month |
after first Avastin. c) one month after second Avastin. d) one month after intravitreal Kenalog. |
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Figure 16: Same patient of Fig. 15. 18 months after Kenalog; 17 months after grid laser photocoagulation.
DME Associated with Posterior Hyaloidal Traction
Vitreomacular traction may cause diffuse macular edema in diabetic patients. The traction is not always clinically obvious at the biomicroscopic examination. The traction is easily visualized on OCT. Laser is ineffective and vitrectomy with stripping of the posterior hyaloid is indicated.
There is subset of patients with thickened, taut, glistening posterior hyaloid on clinical biomicroscopic examination with no posterior vitreous separation.(15) OCT shows tangential traction and a shallow macular detachment
in some cases. Vitreoretinal surgery is often successful at restoring visual acuity.
Vitreous surgery for eyes unresponsive to laser or combined therapy and without evidence of vitreomacular traction is a matter of controversy. Results of several trials comparing pars plana vitrectomy versus laser are inconsistent. The role ILM peeling is not clear. Anatomic improvement may not parallel visual acuity improvement.
Vitrectomy should be considered as a last resort in eyes with severe DME, unresponsive to all therapies. Theoretically, eyes with an attached vitreous should have better surgical outcome, but this has not been demonstrated.
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Figure 18: Long standing, massive lipid deposition at the macula.
Figure 17: Ischemic DME.
DME with Retinal Ischemia
These eyes show an irregular enlargement of the FAZ (foveal avascular zone) with non perfusion of capillaries from the perifoveal net. In spite of capillary closure, dye leakage may be demonstrated in some eyes, probably
derived from the retinal pigment epithelium (Figure 17). The visual outcome is usually poor. Even though some specialists do recommend laser treatment in these cases, we prefer to abstain. Laser treatment should be considered only if there is some demonstrable leakage on fluorescein angiography.
a |
b |
Figure 19: a) Active PDR in spite of a full panretinal laser photocoagulation. b) after vitreous surgery.
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DME with Long Standing, Massive Lipid Deposition at the Macula
Those eyes show and elevated mound of hard exudates at the macula sometimes with highly reflective crystals (Figure 18). The prognosis for recovery of central vision is extremely poor, due to irreparable damage to the photoreceptors.
Diabetic Retinopathy: Indications for Vitrectomy
1.Severe, no clearing vitreous hemorrhage. Prompt vitrectomy and intraoperative photocoagulation is recommended in patients not previously treated with laser, in patients who have lost vision in the other eye, in Type 1 diabetic, and patients with rubeosis iridis.
2.Active, florid proliferative diabetic reti-
nopathy (DPR) that |
persists despite |
|
a full laser |
panretinal |
photocoagulation |
(Figure 19). |
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|
3.If preretinal hemorrhage or a less severe vitreous hemorrhage do not allow an effective photocoagulation therapy.
4.Tractional retinal detachment that involves the macular area.
5.Combined traction-rhegmatogenous retinal detachment.
References
1.Wilkinson CP, Ferris GL, Klein RE, Lee PP, Agardh CD, Davis M, Dills D, Kampik A., Prarajasegaram R, Verdaguer TJ. Proposed International Clinical Diabetic Retinopathy and Diabetic Macular Edema Disease Severity Scales. Ophthalmology 2003; 110: 1667-1682.
2.Diabetic Retinopathy Study Research Group: Preliminary Report on Effects of Photocoagulation Therapy. Am. J Ophthalmol 1976; 81: 383-396.
3.Early Treatment Diabetic Retinopathy Study Research Group. Early Photocoagulation for Diabetic Retinopathy. ETDRS Report Number 9. Ophthalmology 1991; 98: 766-785.
4.Klein R., Klein B, Moss SE, Davis M, De Mets D. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. VII Diabetic Nonproliferative Retinal Lesions. Ophthalmology 1987; 94: 1389-1400.
5.Chew EY, Klein M: Ferris FL et al. Association of elevated serum lipid levels with retinal hard exudates in diabetic retinopathy. ETDRS Report Number 22. Arch. Ophthalmol 1996; 114: 1079-1084.
6.Early Treatment Diabetic Retinopathy Study. Photocoagulation for diabetic macular edema. Early Treatment Report Number 1. Early Treatment Diabetic Retinopathy Study Research Group. Arch Ophthal 1985; 103:1796-1806.
7.Browning DJ, Altawed, MA, Bressler NM, Bressler SB, Scott IU, On behalf of the Diabetic Retinopathy Clinical Research Network. Diabetic macular edema: What is focal and what is diffuse? Am. J. Ophthalmol 2008; 146: 649-655.
8.Early Treatment Diabetic Retinopathy Study Research Group. Focal photocoagulation treatment of diabetic macular edema. Relationship of treatment effect to fluorescein angiographic and other retinal characteristics at baseline: ETDRS report Number 19. Arch. Ophthalmol 1995; 113: 1144.1155.
9.O’Doherty M, Dooley I, Hickey-Dwyer M. Interventions for diabetic macular edema: a systematic review of literature. Br J Ophthalmol. 2008; 92: 1581-1590.
6.Patients with DME and significant vitreomacular traction.
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10.Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal grid photocoagulation for diabetic macular edema. Ophthalmology 2008;
115:1447-59.
11.Gillies MC, Sutter FK, Simpson JM, et al. Intravitreal triamcinolone for refractory diabetic macular edema: two-year results of double-masked placebocontrolled randomized clinical trial. Ophthalmology 2006; 113: 1533-38.
12.Arévalo JF, Sánchez JG, Wu L, Maia M, Alezzandrini AA, Brito M, Bonafonte S, Luján D, Díaz-Llopis M, Restrepo N, Rodríguez FJ, Udaondo-Mirete P; Pan American Collaborative Retina Study Group (PACORES). Primary Intravitreal Bevacizumab for Diffuse Diabetic Macular Edema. The Pan American Collaborative Retina Study Group at 24 Months. Ophthalmology, 2009; published online 6/22/2009.
13.Kang SW, Sa HS, Cho HY et al. Macular grid photocoagulation after intravitreal triamcinolone acetonide for diffuse diabetic macular edema. Arch Ophthalmol 2006; 124: 653-58.
14.Lam DS, Chan CK, Mohamed S et al. Intravitreal triamcinolone plus sequential grid laser versus triamcinolone or laser alone for treating diabetic macular edema: six months outcomes. Ophthalmology 2007; 114: 2162-67.
15.Kaiser PK, Rieman C, Sears SE, Lewis H. Macular traction detachment and diabetic macular edema associated with posterior hyaloid traction. Am. J Ophthalmol. 2001; 131: 44-49.