Prompt Improvement of an Enlarging Pigment Epithelial Detachment Following Intravitreal Dexamethasone in Neovascular Age-Related Macular Degeneration

Abstract

Purpose:

This report discusses a case of neovascular age-related macular degeneration with mixed serous pigment epithelial detachment (PED) that was unresponsive to antivascular endothelial growth injections but responded to the addition of intravitreal steroid injection.

Methods:

We report a case.

Results:

A 75-year-old woman with neovascular age-related macular degeneration developed a mixed serous PED in her right eye. Three monthly aflibercept (Eylea, Regeneron) treatments led to resolution of associated intraretinal fluid; however, the mixed serous and fibrovascular PED significantly increased in size. The addition of intravitreal dexamethasone (Ozurdex, Allergan) to monthly aflibercept led to prompt flattening of the PED. Three months later, the PED recurred despite continued administration of monthly aflibercept.

Conclusions:

This case supports a growing body of research that PEDs unresponsive to antivascular endothelial growth injections may respond to intravitreal steroid injections.

Introduction

The presence of a pigment epithelial detachment (PED) is not uncommon in eyes with age-related macular degeneration (AMD). ¹ Eyes with nonneovascular AMD may have a PED that is of the drusenoid subtype. In eyes with neovascular AMD, however, PEDs may be serous, fibrovascular, hemorrhagic, or mixed-type. ² PEDs associated with choroidal neovascularization in eyes with neovascular AMD are typically treated with intravitreal antivascular endothelial growth factor (anti-VEGF) agents and sometimes photodynamic therapy. ^3,4 Studies examining the efficacies of various anti-VEGF agents in eyes with PEDs due to neovascular AMD have suggested that aflibercept may yield more favorable responses. ⁵ Intravitreal corticosteroid treatment, although less commonly used, has also been described as an effective therapeutic option for serous PEDs associated with neovascular AMD. Here we describe a patient with neovascular AMD and a mixed PED that increased in size while receiving intravitreal aflibercept and promptly improved after the addition of intravitreal dexamethasone.

Methods

A 75-year-old woman developed neovascular AMD associated with a serous and fibrovascular mixed-type PED and intraretinal fluid in the right eye (Figures 1 and 2). Subretinal pigment epithelium hyperreflective material (sub-RPE HRM) was also present. Snellen equivalent of corrected ETDRS (Early Treatment Diabetic Retinopathy Study) visual acuity (VA) in the right eye was 20/64. Monthly intravitreal therapy with aflibercept (Eylea, Regeneron) was administered for 3 consecutive months. After 3 aflibercept injections, the intraretinal fluid resolved; however, the PED had increased significantly in size (Figure 3). Given the recalcitrant nature and height of the mixed-type PED, the decision was made to add an intravitreal 0.7-mg dexamethasone implant (Ozurdex, Allergan) to the treatment regimen and continue intravitreal aflibercept.

Figure 1.

Heidelberg Spectralis spectral domain–optical coherence tomography image of the right eye with neovascular age-related macular degeneration. One month before development of a mixed serous and fibrovascular pigment epithelial detachment, drusen are apparent (arrows).

Figure 2.

Heidelberg Spectralis spectral domain–optical coherence tomography image of the right eye demonstrating a mixed serous and fibrovascular pigment epithelial detachment with a maximum vertical dimension of 289 μm, with some associated overlying intraretinal fluid. Arrows indicate subretinal pigment epithelium hyperreflective material.

Figure 3.

Heidelberg Spectralis spectral domain–optical coherence tomography image of the right eye 1 month after the third of 3 monthly intravitreal aflibercept injections. The mixed pigment epithelial detachment (PED) increased in height with a maximum vertical PED dimension of 630 μm. The subretinal pigment epithelium hyperreflective material has increased (arrows).

Because use of an intravitreal dexamethasone implant in eyes with neovascular AMD is considered off-label, a free sample was administered in our case. Preservative-free triamcinolone acetate (Triesence, Alcon) is another intravitreal steroid that was considered in this case instead of an intravitreal dexamethasone implant; however, the intravitreal dexamethasone implant was chosen by the treating physician (S.F.). Intravitreal triamcinolone acetate (Kenalog, Bristol-Myers Squibb Company) was not considered for off-label use in this case; it is rarely used intravitreally by the authors because it is not preservative free.

Four weeks after administration of the intravitreal dexamethasone implant, the PED promptly flattened (Figure 4). VA remained 20/64. Intraocular pressure was 19 mm Hg. At this point, intravitreal aflibercept was injected, and monthly injections of aflibercept were resumed.

Figure 4.

Heidelberg Spectralis spectral domain–optical coherence tomography image of the right eye 1 month after the addition of intravitreal 0.7-mg dexamethasone implant (Ozurdex, Allergan) to intravitreal aflibercept administration, demonstrating flattening of the mixed pigment epithelial detachment.

Three months after the administration of the intravitreal dexamethasone implant, the mixed-type PED recurred (Figure 5) despite continued monthly aflibercept.

Figure 5.

Heidelberg Spectralis spectral domain–optical coherence tomography image of the right eye 3 months after intravitreal 0.7-mg dexamethasone implant (Ozurdex, Allergan). As the effect of the dexamethasone waned, the mixed serous pigment epithelial detachment recurred despite continued monthly intravitreal aflibercept. Subretinal and intraretinal fluid was present.

Results

This case illustrates progressive growth of a mixed serous and fibrovascular PED in an eye with neovascular AMD despite monthly intravitreal aflibercept. The sub-RPE HRM, indicating the presence of fibrovascular tissue, persisted on optical coherence tomography imaging despite treatment with the anti-VEGF agent aflibercept. Sub-RPE HRM that does not improve with anti-VEGF therapy may serve as a morphological biomarker portending a worse prognosis. ⁶ The addition of an intravitreal dexamethasone implant led to prompt collapse of the PED in that eye.

Although it is possible that the continued administration of monthly intravitreal aflibercept, instead of the addition of intravitreal dexamethasone, led to flattening of the PED, the timing and response to therapy strongly suggest otherwise. First, the PED continued to enlarge relatively rapidly despite receiving 3 monthly injections of aflibercept. Second, the PED flattened promptly after the addition of the dexamethasone implant to the treatment regimen, making its improvement less likely attributable to the fourth intravitreal anti-VEGF injection alone. Finally, the PED recurred 3 months after administration of the intravitreal dexamethasone implant despite continued aflibercept treatment. This 3-month time frame corresponds to the expected time of weakened efficacy of the dexamethasone implant. Taken together, the timing of the dexamethasone implant administration and resolution of the PED in conjunction with the recurrence of the PED 3 months after dexamethasone was administered suggests that the addition of the steroid was most likely responsible for PED improvement (Figure 6).

Figure 6.

Timeline detailing the diagnosis and management of the pigment epithelial detachment. Scale is in months.

Inflammatory processes are theorized to be central to the pathogenesis of neovascular AMD. ^7,8 In eyes with AMD, accumulation of free radicals and oxidized lipoproteins leads to increased oxidative stress, which, when combined with decreased intracellular recycling and attenuated autophagy of the aging eye, leads to eventual degeneration of the retinal pigment epithelium and in some cases, choroidal neovascularization. ⁷ This degeneration is thought to be largely mediated by elevation in levels of inflammatory molecules and recruitment and activation of macrophages and microglia, particularly in the macula. ⁹

Although the exact mechanism of action of corticosteroids is not completely understood, their anti-inflammatory, antiangiogenic, antifibrotic, and antipermeability properties are often of benefit in the treatment of ocular conditions associated with macular edema and angiogenesis. ¹⁰ “Triple therapy,” in which patients with AMD receive intravitreal dexamethasone or triamcinolone acetonide injections, intravitreal bevacizumab or other anti-VEGF injections, and photodynamic therapy, has been described to stabilize and sometimes improve VA in eyes with neovascular AMD that does not respond to anti-VEGF treatment alone. ^11,12

Furthermore, previous reports have shown that even intravitreal steroid injections on their own may lead to PED resolution. Pasyechnikova and colleagues ¹³ treated 19 eyes with serous PEDs due to AMD with intravitreal triamcinolone acetonide monotherapy, leading to PED resolution in 37% of eyes and decreased PED size in each of the other treated cases. In our reported case, it is possible that the added anti-inflammatory and antipermeability properties of intravitreal dexamethasone combined with the antiangiogenic properties of anti-VEGF treatment were all necessary for the collapse of the PED.

It has been suggested that treatment with aflibercept results in PED resolution in eyes with neovascular AMD, ^{5,14 -16} yet in our case it was not effective as monotherapy. It is more likely that as the dexamethasone implant began to decrease in efficacy 3 months following its injection, the inflammatory component returned, driving recurrence of the PED. ¹⁷

Conclusions

This case report suggests that the addition of an intravitreal steroid may be an effective therapeutic strategy for mixed-type PEDs resistant to anti-VEGF treatment alone. Further work may help elucidate the role of corticosteroids in the combination treatment of eyes with neovascular AMD compared with anti-VEGF treatment alone.