Lamellar macular hole is a rare entity that is characterized by a partial defect of the inner retinal tissue in the fovea. In patients with long-standing diabetic cystoid macular edema, the presence of a thin epiretinal membrane and a posterior hyaloid membrane on the thinned inner wall of the cystoid space were described as common characteristics that could contribute to the spontaneous transformation to lamellar macular hole.1
We report a case of lamellar macular hole following the use of intravitreal bevacizumab injection for diabetic cystoid macular edema in a patient with preexisting posterior vitreous detachment that was previously documented by optical coherence tomography (OCT).
A 49-year-old woman with diabetes mellitus who had previously received panretinal photocoagulation for proliferative diabetic retinopathy, grid laser photocoagulation, and three intravitreal bevacizumab injections in each eye for the treatment of cystoid macular edema presented with the appearance of a macular hole in her left eye 1 month after the last bevacizumab injection (Figure 1A). OCT demonstrated a lamellar macular hole with disappearance of the cystoid space in her left eye (Figure 1B). Previous OCT scans that were taken 1 month before revealed a large cystoid space beneath the foveal region (Figure 2A). Visual acuity, which was 20/125 before injection, improved to 20/100. OCT scans performed 3 months prior to presentation showed complete separation of the posterior hyaloid membrane from the retinal surface (Figure 2B).
Figure 1. (A) Fundus photography showing the appearance of a macular hole. (B) Optical coherence tomography scan demonstrating a lamellar macular hole.
Figure 2. (A) Optical coherence tomography (OCT) scan showing cystoid macular edema with a large central cystoid cavity 1 month before intravitreal bevacizumab injection. (B) OCT scan obtained 3 months prior to the development of lamellar macular hole demonstrating cystoid macular edema and posterior hyaloid membrane detachment.
We report a case of lamellar macular hole that was detected following three intravitreal bevacizumab injections for the treatment of diabetic cystoid macular edema in a patient without vitreomacular traction, which was previously documented with OCT.
Since the first case report of lamellar macular hole secondary to cystoid macular edema after cataract extraction by Gass in 1975, the development of lamellar macular hole has been described in different retinal disorders associated with chronic cystoid macular edema, including diabetic retinopathy and retinal vein occlusion.1–4 Although the exact mechanism remains unclear, the presence of a coexisting epiretinal membrane or vitreomacular traction that causes rupture of the thinned inner wall of the cystoid cavity has been described as a possible mechanism for transformation from cystoid macular edema to lamellar macular hole.1,3–4
In a case report of a full-thickness macular hole that developed after intravitreal triamcinolone injections for diabetic cystoid macular edema, the authors postulated that repeated injections might have had an indirect role in macular hole formation by favoring the rupture of distended Müller cells and intraretinal pseudocysts.5 In another case report, lamellar macular hole transformation was described following pegaptanib injection for the treatment of diabetic cystoid macular edema in a patient without pretreatment who displayed clinically detectable vitreomacular traction.6 In our case, given the OCT findings that demonstrated posterior vitreous detachment and the absence of epiretinal membrane or vitreomacular traction, it may be suggested that the tractional forces on the fovea are less likely to contribute to the development of lamellar macular hole.
In a post-mortem study of two patients with diabetic cystoid macular edema, Yanoff et al. reported that cystoid cavity formation might be caused by the liquefaction necrosis of Müller cells and adjacent neural cells due to persistent edema or ischemia.7 In eyes with well-established diabetic cystoid macular edema, the cystoid spaces fuse to form a large cystoid cavity that may involve the entire retinal layer, and the remaining retinal tissue becomes atrophic.8 It may be postulated that this progressive process of retinal thinning may result in the spontaneous rupture of the inner wall of the cystoid structure.
In recent case reports, full-thickness macular hole formation has been described after intravitreal injections of anti-vascular endothelial growth factor agents in the treatment of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.9–13 On the other hand, in a case reported by Walter et al., macular hole formation has been documented during the natural course of the choroidal neovascularization secondary to age-related macular degeneration without any intravitreal injection.14 In another recent study, foveal atrophy and macular hole formation have been demonstrated in patients treated with recurrent ranibizumab injections with or without photodynamic therapy for choroidal neovascularization.15 In a study by Forooghian et al., intravitreal bevacizumab injection has been found to be associated with increased concentrations of inflammatory cytokines, which may be associated with fibrosis and scar formation in eyes with proliferative diabetic retinopathy.16 This contraction effect on the atrophic retinal tissue may be associated with rupture of the large cystoid space and progression to lamellar macular hole.
Although there is insufficient evidence to establish a causal relationship between intravitreal bevacizumab injection and transformation to lamellar macular hole, it may be suggested that progressive retinal thinning that leads to lamellar or full-thickness macular hole formation might be induced or facilitated by repeated injections of bevacizumab in patients with long-standing diabetic cystoid macular edema. Further studies are needed to fully describe the possible adverse effects of bevacizumab injection in the treatment of diabetic cystoid macular edema.
- Unoki N, Nishijima K, Kita M, et al. Lamellar macular hole formation in patients with diabetic cystoid macular edema. Retina. 2009;29:1128–1133. doi:10.1097/IAE.0b013e3181a4d2d9 [CrossRef]
- Androudi S, Stangos A, Brazitikos PD. Lamellar macular holes: tomographic features and surgical outcome. Am J Ophthalmol. 2009;148:420–426. doi:10.1016/j.ajo.2009.04.009 [CrossRef]
- Gass JD. Lamellar macular hole: a complication of cystoid macular edema after cataract extraction: a clinicopathologic case report. Trans Am Ophthalmol Soc. 1975;73:231–250.
- Tsukada K, Tsujikawa A, Murakami T, Ogino K, Yoshimura N. Lamellar macular hole formation in chronic cystoid macular edema associated with retinal vein occlusion. Jpn J Ophthalmol. 2011;55:506–513. doi:10.1007/s10384-011-0056-9 [CrossRef]
- Lecleire-Collet A, Offret O, Gaucher D, Audren F, Haouchine B, Massin P. Full-thickness macular hole in a patient with diabetic cystoid macular oedema treated by intravitreal triamcinolone injections. Acta Ophthalmol Scand. 2007;85:795–798. doi:10.1111/j.1600-0420.2007.00925.x [CrossRef]
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- Yanoff M, Fine BS, Brucker AJ, Eagle RC Jr, . Pathology of human cystoid macular edema. Surv Ophthalmol. 1984;28(suppl):505–511. doi:10.1016/0039-6257(84)90233-9 [CrossRef]
- Otani T, Kishi S, Maruyama Y. Patterns of diabetic macular edema with optical coherence tomography. Am J Ophthalmol. 1999;127:688–693. doi:10.1016/S0002-9394(99)00033-1 [CrossRef]
- Cho JH, Park SE, Han JR, Kim HK, Nam WH. Macular hole after intravitreal ranibizumab injection for polypoidal choroidal vasculopathy. Clin Exp Optom. 2011;94:586–588. doi:10.1111/j.1444-0938.2011.00614.x [CrossRef]
- Clemens CR, Holz FG, Meyer CH. Macular hole formation in the presence of a pigment epithelial detachment after three consecutive intravitreal antivascular endothelial growth factor injections. J Ocul Pharmacol Ther. 2010;26:297–299. doi:10.1089/jop.2009.0140 [CrossRef]
- Grigoropoulos V, Emfietzoglou J, Nikolaidis P, Theodossiadis G, Theodossiadis P. Full-thickness macular hole after intravitreal injection of ranibizumab in a patient with retinal pigment epithelium detachment and tear. Eur J Ophthalmol. 2010;20:469–472.
- Moisseiev E, Goldstein M, Loewenstein A, Moisseiev J. Macular hole following intravitreal bevacizumab injection in choroidal neovascularization caused by age-related macular degeneration. Case Report Ophthalmol. 2010;1:36–41. doi:10.1159/000319827 [CrossRef]
- Querques G, Souied EH, Soubrane G. Macular hole following intravitreal ranibizumab injection for choroidal neovascular membrane caused by age-related macular degeneration. Acta Ophthalmol. 2009;87:235–237. doi:10.1111/j.1755-3768.2008.01226.x [CrossRef]
- Walter HS, Gatzioufas Z, El-Husseiny M, Stavridis E, Seitz B. Does intravitreal injection of ranibizumab increase the risk for macular hole formation?Eur J Ophthalmol. 2011;21:680–681. doi:10.5301/EJO.2010.6071 [CrossRef]
- Rishi P, Kasinathan N, Sahu C. Foveal atrophy and macular hole formation following intravitreal ranibizumab with/without photodynamic therapy for choroidal neovascularization secondary to age-related macular degeneration. Clin Ophthalmol. 2011;5:167–170. doi:10.2147/OPTH.S16947 [CrossRef]
- Forooghian F, Kertes PJ, Eng KT, Agron E, Chew EY. Alterations in the intraocular cytokine milieu after intravitreal bevacizumab. Invest Ophthalmol Vis Sci. 2010;51:2388–2392. doi:10.1167/iovs.09-4065 [CrossRef]