CME is a complication of RP occurring in 10-20% of patients [
2]. Currently there is not a gold-standard therapeutic option and treatment response seems to be individualized. Many caregivers deem carbonic anhydrase inhibitors to be the mainstay of treatment. Yet, many are the patients who fail to respond to carbonic anhydrase inhibitors therapy [
9,
10,
22,
23]. Additionally, considering their adverse effects, their use is discouraged. The same is true for IVT [
2,
15,
16]. During the last few years, a limited amount of studies have tested VEGF inhibitors in the management of CME secondary to RP with generally good results [
22,
23,
28]. In 2007, Melo et al. [
29], presented two eyes of two different cases, in which intravitreal bevacizumab (AVASTIN; Genentech, South San Francisco, California, USA) was tested. The first patient failed to achieve an increase in visual acuity (VA, 2/200 pre- and post-injection) or decrease in retinal thickness (524 μm and 529 μm pre- and post-injection, respectively) after follow-up of one month, while in the second patient VA deteriorated from 2/100 to 2/200 and retinal thickness increased from 282 μm to 299 μm one month after the injection. Both patients showed ambiguous improvement with IVT. However, in 2009, Yuzbasioglu et al. [
28] followed 13 eyes of 7 patients treated with intravitreal bevacizumab for a period of 10.3 months. VA increased from 5/400-20/100 to 20/200-20/63 and central macular thickness decreased from 245–603 μm to 124–168 μm. Other anti-VEGF agents have also been tested in CME secondary to RP, such as pegaptanib sodium (MACUGEN; EyeTech Pharmaceutical, Inc., New York, USA); particularly, Querques et al. [
22] presented a case refractory to oral acetazolamide (1 month, 500 mg daily) with baseline BCVA 2/200 in his left eye (the one with the CME). One dose of intravitreal pegaptanib sodium 0.3 mg lead to improvement in BCVA to 20/40 and resolution of CME as seen with fundus microscopy and optical coherence tomography (OCT). Oral acetazolamide was continued for an additional month, and two months after acetazolamide withdrawal and 4 months after the pegaptanic sodium injection, BCVA still maintained at 20/40 and no recurrence of the CME was noticed. A cohort study reporting on the use of anti-VEGF agents in CME-RP was conducted in 2009 by Artunay et al. [
23], who used intravitreal ranibizumab (LUCENTIS; Genentech, South San Francisco, California, USA) in 15 eyes of 15 patients with persistent edema at least 6 months despite acetazolamide therapy. 15 eyes of 15 similar patients who refused this off-label treatment were considered the control group. 6 months after one dose of intravitreal ranbizumab 0.5 mg, both central foveal thickness and BCVA showed improvement, although improvement of BCVA was not statistically significant (p > 0.05). However, none of the studies above used aflibercept for this condition and none of the studies used multifocal-electroretinogram to assess retinal function.
Aflibercept is a chimeric protein consisted of the extracellular portion of the human VEGF receptors 1 and 2 (binding section) and the Fc portion of IgG1 immunoglobulin [
30]. This structure ensures a very high VEGF binding affinity [
27]. Furthermore, its long duration of action makes it an interesting new agent, since it may reduce frequency of repeat injections if needed, and establish a more durable effect [
26,
27]. Most frequent adverse reactions (≥5%) that have been observed with intravitreal aflibercept injection are conjunctival hemorrhage, eye pain, cataract, vitreous floaters, and transiently increased intraocular pressure [
31]. Severe adverse events, such as endophthalmitis and retinal detachment are rare (<0.1%) [
31]. Currently, aflibercept has been approved by the US Food and Drug Administration (FDA) for the management of neovascular (wet) age-related macular degeneration (2011), diabetic macular edema (2014) and macular edema following retinal vein occlusion (2014). No testing has been made on macular edema associated with RP and this case report is the first clue of efficacy of aflibercept. Our patient showed a 10% improvement in BCVA and significant resolution of macular edema in OCT scan, although mfERG response remained decreased (yet, better-shaped peaks and no areas of eccentral vision).
Our results show that there are anatomical correlates to support the concept of macular edema amelioration. This is mainly the prominent decrease of macular thickness as measured by OCT. The mean visual acuity improved only by 10% one month after treatment and remained unchanged two months later. On the contrary, mfERG findings did not follow the decrease of macular thickness. These findings show that the increase of visual acuity, as also the improvement of electrical responses of the macular area did not follow the decrease of macular thickness. This may be explained by the fact that macular edema is only a parameter that may affect visual acuity and electrophysiological responses in the beginning of the disease. Atrophy of the retina, particularly of the photoreceptors, atrophy of the pigment epithelium and scarring are all unmeasured variables, which have potential to impact vision. Of course, we are not able to definitely conclude on the issue, merely based on this case and further studies with larger samples and a longer follow-up period are needed for this reason. However the anatomical improvement is very promising and further investigation must be done.