From the Department of Ophthalmology, “G. Gennimatas” Hospital, University of Athens, Athens, Greece.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Ilias Georgalas, MD, Consultant Vitreoretinal Surgeon, 59 Chrysanthemon str, 15452 Athens, Greece.
Central retinal vein occlusion (CRVO) is one of the most common retinal vascular disorders. Loss of central vision may be due to macular ischemia or neovascular complications but the major cause of visual loss is cystoid macular edema (CME). Intravitreal anti-VEGF (vascular endothelial growth factor) agents have recently been applied as a promising treatment to macular edema due to CRVO.1,2 Ocular and systemic side effects (such as hypertension and cerebral infraction) have been reported after intravitreal injections of Bevacizumab for the treatment of several ocular diseases.2–8
We report the development of a full thickness macular hole (FTMH) after treatment with a single intravitreal injection of Bevacizumab in a 44-year-old patient with CME secondary to CRVO and describe its course after vitrectomy ILM peeling and gas tamponade.
A 44-year-old man referred with a 3-day history of painless decreased vision in his left eye (LE). He denied any history of systematic illness apart from high homocysteine levels. On examination, best corrected visual acuity (BCVA) was 1/60 LE. Anterior segment examination was unremarkable and fundoscopy of the LE revealed a central retinal vein occlusion (CRVO) with cystoid macular edema (CME). There was no posterior vitreous detachment (PVD). Fluorescein angiography (FA) showed macular edema and optical coherence tomography (OCT) demonstrated a massive macular edema without any tractional element (Figs. 1A and 1B).
Figure 1. (A) Red Free Fundus Photo Shows Central Retinal Vein Occlusion and Macular Edema (B) Optical Coherence Tomography(OCT) Demonstrates Macular Edema Without Any Areas of Partial Vitreous Separation Associated with Vitreoretinal Adhesions.
An intravitreal injection of 1.25 mg Bevacizumab was performed and 2 months later BCVA improved to 6/12 corresponding with the decreased macular edema. However, in the OCT apart from the decreased retinal thickness, a small full thickness deficit of the retina was noted (Fig. 2).
Figure 2. Two Months After Intravitreal Injection of Bevacizumab, OCT Shows Resolving Macular Edema Corresponding with the Improved Visual Acuity. However, a Small Full Thickness Deficit of the Retina in the Foveal Area is Evident.
Conservative management was undertaken at that time. Three months later, BCVA deteriorated to 6/60 and slit-lamp biomicroscopy revealed an full thickness macular hole (FTMH) with no posterior vitreous detachment (Fig. 3A). Optical coherence tomography confirmed the presence of an FTMH and failed to identify any areas of partial vitreous separation associated with vitreoretinal adhesions or areas of vitreous traction in any OCT scan (Fig. 3B).
Figure 3. Five Months After the Intravitreal Injection of Bevacizumab a Full Thickness Macular Hole has been Developed as Shown in the Fundus Photo(A) and in the OCT(B).
A 20-gauge-vitrectomy was performed with induction of PVD using the vitreous cutter to engage and pull on the peripapillary vitreous. A volume of 0.3 mL of trypan blue was injected in the vitreous cavity over the posterior pole and removed 2 minutes later. No epiretinal membrane was seen and internal limiting membrane was peeled off from the macular area. Perfluoropropane C3F8 gas 14% was used as a tamponade and the patient was instructed to adopt prone positioning for 7 days.
Two months later, BCVA had improved to 6/18 and the FTMH was closed (Fig. 4). However, OCT showed that the retina was still edematous and presented cystic changes (Fig. 4).
Figure 4. Two Months After Vitrectomy Surgery, the Full Thickness Macular Hole is Closed. However, the Retina in the Macular Area is Still Edematous and has Cystic Changes.
A second intravitreal injection of 1.25 mg Bevacizumab was performed resulting in a further improvement in BCVA (6/12) with complete resolution of macular edema (Fig. 5). Eight months later, the visual acuity remained 6/12.
Figure 5. Two Months After a Second Intravitreal Injection of Bevacizumab, OCT Demonstrates Almost Complete Resolution of the Macular Edema.
Pathogenesis of idiopathic FTMH relies on anterior-posterior traction by the vitreous on the macula.9,10 Only a few cases with FTMH associated with macular edema have been reported in the literature and their pathogenetic mechanism remains unclear.9,11 A macular hole can develop following a retinal vein occlusion, usually as a complication of chronic cystoid macular edema.12 Leibovitch et al. 13 reported a lamellar macular hole due to a macular edema following branch retinal vein occlusion and a horseshoe-like tear in the fovea, which occurred after a recurrent retinal vein occlusion, was observed by Karim-Zade et al.14
Rapid progression of an FTMH has been reported once in the literature after intravitreal injections of triamcinolone acetonide for the treatment of macular edema in a patient with CME due to CRVO. Lattanzio et al.15 hypothesized that the progression of the FTMH in their 33-year-old patient could be attributed to the combination of rapid retinal thinning due to CME, to vitreal traction and the authors also conjectured mechanical effects of the IVTA on the vitreous surface.
Lecleire-Collet et al.16 have reported a 48-year-old patient with diabetic maculopathy who developed an FTMH after repeated IVTA. The authors postulated that this could be the result of several factors such as retinal thinning, epiretinal membrane formation, vitreoschisis and have also pointed out that repeated intravitreal injections of triamcinolone may had played an additional indirect role in the development of FTMH.
In our 44-year-old patient, the FTMH developed after a single intravitreal injection of Bevacizumab for the treatment of CME due to CRVO. There was no evidence on examination or in OCT scans of any vitreoretinal traction or partial PVD at any stage.
We postulate that the formation of FTMH in our patient could be explained by a mechanism similar to the one described above after IVTA. The retinal changes due to the massive CME, the absence of PVD in combination with the vitreous traction induced either by the mechanical globe deformation and vitreous synaeresis or by a possible vitreous incanceration at the injection site, could lead to the development of FTMH. The fact that in our case and in all reported cases, the patients who developed FTMH after intravitreal injections were relatively young, should also be taken into consideration.
Our case illustrates the potential for development of an FTMH in patients with CME due to CRVO treated with intravitreal injections of Bevacizumab, which to the best of our knowledge has never been reported before. It also strengthens the view that the development or progression of FTMHs in patients with CME treated with intravitreals is more likely to be due to the mechanical effect of the intravitreal injection itself rather than a result of the medication used, since this complication has also been reported after IVTAs. Additionally, in our case vitrectomy surgery combined with ILM peeling and gas tamponade was beneficial for the patient’s vision and achieved closure of the FTMH. Although the incidence is rare, careful examination of the status of the vitreous and search for signs of PVD with fundoscopy and OCT might be advocated, especially in younger patients treated with intravitreal injections because these patients seem to be more prone to develop this complication.
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