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Year : 2019  |  Volume : 6  |  Issue : 2  |  Page : 52-56

Treatment of macular edema caused by leber's miliary aneurysms using intravitreal aflibercept and peripheral laser photocoagulation

Department of Ophthalmology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Date of Submission16-Dec-2019
Date of Acceptance20-Jan-2020
Date of Web Publication19-Feb-2020

Correspondence Address:
Dr. Ahmed M Abdelhadi
Department of Ophthalmology, Alexandria University, Sidi Gaber 21311, Alexandria
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/erj.erj_13_19

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Purpose: This study aims to determine if intravitreal aflibercept (IVA) is effective in the treatment of macular edema (ME) caused by Leber's miliary aneurysm (LMA), augmented with peripheral laser photocoagulation for the abnormal vessels. Subjects and Methods: This prospective interventional noncomparative case series included 6 eyes of 6 patients with a clinical diagnosis of LMA, based on fluorescein angiography and optical coherence tomography (OCT) findings. Laser photocoagulation was performed to the aneurysms, except those near the fovea. Three to five IVA injections were needed to dry off the macula. Serial color fundus photography and OCT were performed to measure treatment efficacy. Results: After 3–5 IVA, the ME responded marvelously in all patients. One patient had recurrent ME 3 months later, for which an additional 2 IVA was needed. Again one session of ablative laser for diseased vessels was enough for all except for one patient who needed supplemental laser therapy 4 months later. Improved visual acuity was noted in all cases without reported ocular or systemic complications. Conclusion: IVA with peripheral laser ablation appears to be an effective treatment for patients with LMA, as it has the potential to improve final visual acuity.

Keywords: Aflibercept, Leber's miliary aneurysms, macular edema

How to cite this article:
Abdelhadi AM. Treatment of macular edema caused by leber's miliary aneurysms using intravitreal aflibercept and peripheral laser photocoagulation. Egypt Retina J 2019;6:52-6

How to cite this URL:
Abdelhadi AM. Treatment of macular edema caused by leber's miliary aneurysms using intravitreal aflibercept and peripheral laser photocoagulation. Egypt Retina J [serial online] 2019 [cited 2021 Dec 2];6:52-6. Available from: https://www.egyptretinaj.com/text.asp?2019/6/2/52/278677

  Introduction Top

Leber's miliary aneurysms (LMA), a diseasefirst described in 1912 as a separate entity from Coats disease.[1] Later, both were grouped in a single disease spectrum called primary retinal telangiectasias. LMA most commonly occur in one eye in males around the fourth decade of life. They are most frequently localized in the temporal hemiretina, near the equator. The diagnosis is made with a fundus examination and fluorescein angiography (FA) assessment, which show multiple aneurysms with chronic and localized extravasation that gives rise to hard exudates. In the early stage of FA, there is hyper-fluorescence around vascular dilatations; at later stages a there is diffusion of contrast from the telangiectasia, which may cause cystoid macular edema (CME). Leber's aneurysm resembles type 1 idiopathic macular telangiectasia (IMT) in several aspects. Gamulescu et al.[2] reported a case of type 1 IMT that had remarkably improved following an intravitreal injection of bevacizumab (IVB). In addition, Lin et al.[3] also concluded that IVB was a well-tolerated treatment for children with Coats' disease, but the ME recurred shortly in his three cases after initial improvement.

The purpose of this study was to determine if intravitreal aflibercept (IVA) was effective in the treatment of a macular edema caused by LMA, in addition to peripheral laser photocoagulation for the abnormal vessels and microaneurysms.

  Subjects and Methods Top

This prospective interventional noncomparative case series included 6 eyes of 6 young patients (age range: 14–23 years) with unilateral gradual diminution of vision and a clinical diagnosis of abnormal peripheral vasculopathy. On examination, FA revealed many aneurysms with leakage in the temporal mid-peripheral retina and near the macula. Optical coherence tomography (OCT) showed moderate to marked CME and subretinal fluid. There were no abnormal findings in the cornea, anterior chamber, or lens. No particular lesions were found in the opposite eye of each subject. Based on these findings, the patients were diagnosed with LMA.

Three intravitreal injections of aflibercept were given to all included eyes, 1 month apart, to dry the macula.

We performed laser photocoagulation of the aneurysms, except near the fovea, 2 weeks from the initial injection utilizing the IQ 577™ laser (IRIDEX Corporate, Mountain View, CA, USA). The laser parameters were as follows: endpoint, whitening of the retina at the region of the aneurysms; spot size, 500 microns; with one-half to one spot diameter spacing; duration, 100m seconds. Utilizing the Volk super quad lens (Volk Optical, Inc., OH, USA), shots were done to cover the entire area of the aneurysms.

Thefirst OCT was performed 2 months after the third injection. If edema still persisted, another 1–2 injections of aflibercept were administered, 1 month apart; OCT was performed at 1 month postinjection to assess its efficacy. If the macula was found to be dry based on thefirst OCT, another OCT was performed 2–3 months later to identify any recurrence of edema.

FA was conducted with thefirst OCT to assess the need for further treatment with laser therapy; the criteria for laser treatment included the presence of leakage from the microaneurysms that increased in intensity and size in the late frames, indicating nonobliterated aneurysms, which might lead to edema recurrence if not properly ablated. Patients' visual acuity was reported in the logarithm of the minimum angle of resolution (logMAR) for the purpose of statistical analysis.

The study protocol was reviewed by the Alexandria University Ethics Committee, and the study was conducted in accordance with the Declaration of Helsinki. All patients included in the study gave informed consent after being given a clear and thorough explanation of the research protocol.

Written informed consent for patient information and images was provided by the patients or their legal guardians.

To the best of our knowledge, these are thefirst reported cases in which IVA injection therapy was used to treat a macular edema caused by LMA.

  Results Top

Each of the patients included in the study underwent one session of ablative laser therapy for diseased vessels. One patient (Patient 6) required supplemental laser therapy after 4 months from thefirst session. After three aflibercept injections, the subretinal fluid completely reabsorbed in patients 1–3 [Figure 1].
Figure 1: (A) 19 year old male, decrease in VA, OS 6 months ago, OCT with CMT of 509 um. (B) After three monthly IV Aflibercept injections and light laser photocoagulation in the region of the aneurysms, CMT improved to 269 μm, VA improved to 6/24. (C) A follow up OCT done after another 2.5 months showing a stable condition with more improvement of VA to 6/18

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Patients 4 and 5 had persistent subretinal fluid at 2 months following the third aflibercept injection, for which two additional injections were needed to dry the macula [Figure 2]. Patient 6 exhibited recurrence of retinal edema at 4 months after an initial good response from the three IVA injections and needed two additional injections to regain the best visual acuity and reach a normal macular thickness and profile by OCT [Figure 3].
Figure 2: Patient number 4: (A) Pre injection: Colour fundus photo and FA showing the clinical diagnosis of leber military aneurysm in a 21-year-old male with BCVA of 6/36, OCT of the macula shows sub retinal fluid with CMT of 583 microns. (B) After 3 IVA and peripheral laser ablation, Some improvement, but still moderate edema, CMT 445 μm and the same VA of 6/36. (C) After another 2 IVA injections, sub macular hard exudates decreased with Improvement of BCVA to 6/18 after 5.5 months of treatment initiation with resolution of macular edema and CMT of 211 microns

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Figure 3: Patient 5: (A) A 16-year-old female with diminution of vision three months ago in the left eye with BCVA of 6/36, OCT shows sub-retinal fluid with inner retina cystoid edema and hyperreflective hard exudates, CMT of 739 μm. (B) after 3 IVA injections, CMT improved to 222 μm with a corresponding improvement of VA to 6/18. (C) Four months from the last injection, patient 6 started to complaint of mild drop of BCVA to 6/18, with an increase in the CMT by OCT to 350 μm. (D) OCT of the macula showing regain of normal macular thickness of 268 μm after an additional two IVA injections, with return of VA to 6/12. Again, after the sub-retinal fluid resorb, central shifting of the foveal hard exudate with change of the final foveal contour was noticed

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The best-corrected visual acuity (BCVA) improved from a mean ± standard deviation (SD) of +0.83 ± 0.033 logMAR preinjection to a mean ± SD of +0.45 ± 0.034 logMAR postinjection. The preoperative mean line score was 9.6, while the postoperative line score was 14.5 with an improvement of 4.83 ± 0.4. The central macular thickness (CMT) decreased from a preinjection mean ± SD of 588.6 ± 37.77 um to 268.8 ± 11.27 um postinjection. Three subjects (50%) received 3 injections, and three subjects (50%) received 5 injections. All patients underwent one laser session; however, one patient underwent an additional session. The follow-up ranged from 7 to 9 months with an average of 7.5 months.

Improved visual acuity was noted in all cases. No ocular or systemic complications related to IVA injection therapy were noted during the entire treatment course or the follow-up periods. The follow-up period for all patients ranged from 7 to 9 months with a mean of 7.5 months. It was noted that after the subretinal fluid resorption, there was an accumulation of subfoveal hard exudates; nevertheless, the improvement of BCVA had occurred. [Table 1] shows the patients' characteristics, together with pre- and post-injection BCVA and CMT.
Table 1: Patients' characteristics, pre- and post-injection best-corrected visual acuity, and central macular thickness

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  Discussion Top

Eyes determined to have LMA s should be differentiated from other causes of primary and secondary retinal aneurysms. In contrast with Leber's aneurysms, juxta foveal telangiectasias (JFT) present in the posterior pole (causing an earlier reduction of vision) and generally occur in people over 40 years of age. The angiographic view in JFT is different, as it exhibits small vascular dilatations in the perifoveal area.[4] Coats' disease is the most severe of all three primary vasculopathies, and it predominantly affects the pediatric population.

In addition, there is greater visual compromise and poorer prognosis associated with this condition; this is because of the presence of larger and more extensive exudates, which may result in retinal detachment.[5] Some forms of Coats' disease have been described in adults, though with smaller functional repercussions; however, the number of aneurysms and exudates is much greater than that associated with Leber's aneurysms.[6] The differential diagnosis must comprise other vascular diseases, such as venous occlusion, retinal capillary and cavernous haemangiomas, and radiation-induced retinopathy with microaneurysms.[3]

In the current case series, photocoagulation was applied to the aneurysms, despite the focal nature of the disease and the limited exudation present; this was decided after considering that the field defect would be minimal and to avoid subsequent complications. Laser scars should not be very intense to avoid damage of Bruch's membrane and subsequent development of neovascularizations and proliferations.[7] Each of the six patients underwent one session of ablative laser therapy for diseased vessels, and one patient needed supplemental laser therapy at 4 months after the initial session.

The development of this condition is generally slow and can go unnoticed until later periods in life. The prognosis depends on the level of foveal compromise by the exudates, macular edema, vitreomacular traction, or epiretinal membrane.[3],[8],[9] Other complications include thrombosis of the aneurysms, neovascularization, hemorrhage in the vitreous, and progression to Coats' disease.

Treatment options mentioned in the literature include the ablation of the aneurysms by argon laser photocoagulation if the exudates compromise the macula. In some cases, triamcinolone or intravitreous antiangiogenics can be administered; vitreoretinal surgery may be indicated in the presence of macular traction or epiretinal membranes. If the aneurysms are located in the periphery, cryotherapy can be considered.[3]

In all six cases, it was noticed that after the subretinal fluid resorb, the accumulation of subfoveal hard exudates ensues [Figure 1]. The centireptal movement in macular hard exuadats was noticed during treatment before the actual reduction in their density by clinical exam or by OCT [Figure 2].

Similar findings were noticed by Pemp et al.,[10] in diabetic macular edema reduction during intravitreal anti-vascular endothelial growth factor therapy. This was accompanied by the dynamic rearrangement of intraretinal exudates.

Another case report by Lee et al.,[11] reporting a peculiar vascular sheathing at the periphery in a case with findings at the posterior pole resembling those of LMA with a favorable response to triamcinolone, all points to evidence for an inflammatory condition.

  Conclusion Top

IVA (from 3 to 5 injections) with peripheral laser ablation appears to be a well-tolerated treatment for patients with LMA s. Moreover, it has the potential to improve the final visual acuity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given his consent for his images and other clinical information to be reported in the journal. The patients understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interes

  References Top

Coats G. Forms of retinal diseases with massive exudation. R Lond Ophthalmic Hosp Rep 1908;17:440-525.  Back to cited text no. 1
Gamulescu MA, Walter A, Sachs H, Helbig H. Bevacizumab in the treatment of idiopathic macular telangiectasia. Graefes Arch Clin Exp Ophthalmol 2008;246:1189-93.  Back to cited text no. 2
Lin CJ, Hwang JF, Chen YT, Chen SN. The effect of intravitreal bevacizumab in the treatment of Coats disease in children. Retina 2010;30:617-22.  Back to cited text no. 3
Black GC, Perveen R, Bonshek R, Cahill M, Clayton-Smith J, Lloyd IC, et al. Coats' disease of the retina (unilateral retinal telangiectasis) caused by somatic mutation in the NDP gene: A role for norrin in retinal angiogenesis. Hum Mol Genet 1999;8:2031-5.  Back to cited text no. 4
Shields JA, Shields CL, Honavar SG, Demirci H, Cater J. Classification and management of Coats disease: The 2000 Proctor Lecture. Am J Ophthalmol 2001;131:572-83.  Back to cited text no. 5
Lai CH, Kuo HK, Wu PC, Kuo ML, Chen YJ. Manifestation of Coats' disease by age in Taiwan. Clin Exp Ophthalmol 2007;35:361-5.  Back to cited text no. 6
Kolár P, Vlková E. Leber's miliary aneurysms – Case report. Cesk Slov Oftalmol 2003;59:127-33.  Back to cited text no. 7
Mrejen S, Metge F, Denion E, Dureau P, Edelson C, Caputo G. Management of retinal detachment in Coats disease. Study of 15 cases. Retina 2008;28:S26-32.  Back to cited text no. 8
Takeyama M, Iwaki M, Zako M. Intravitreal injection of bevacizumab to treat a macular edema caused by Leber's Miliary aneurysm. Case Rep Ophthalmol 2012;3:392-5.  Back to cited text no. 9
Pemp B, Deák G, Prager S, Mitsch C, Lammer J, Schmidinger G, et al. Distribution of intraretinal exudates in diabetic macular edema during anti-vascular endothelial growth factor therapy observed by spectral domain optical coherence tomography and fundus photography. Retina 2014;34:2407-15.  Back to cited text no. 10
Lee A, Baek J, Ra H. A case of Leber's miliary aneurysms with diffuse peripheral retinal vascular sheathing. Indian J Ophthalmol 2018;66:1496-8.  Back to cited text no. 11
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