1. Volume 122, Issue 9, Pages 1907-1916 (September 2015)
Serous Retinopathy Associated with Mitogen-Activated Protein Kinase Kinase Inhibition (Binimetinib) for Metastatic Cutaneous and Uveal Melanoma 
Elon H.C. van Dijk, MD, Carla M.L. van Herpen, MD, PhD, Marina Marinkovic, MD, John B.A.G. Haanen, MD, PhD, Drake Amundson, BSc, Gré P.M. Luyten, MD, PhD, Martine J. Jager, MD, PhD, Ellen H.W. Kapiteijn, MD, PhD, Jan E.E. Keunen, MD, PhD, Grazyna Adamus, PhD, Camiel J.F. Boon, MD, PhD 
Ophthalmology 
Volume 122, Issue 9, Pages (September 2015)
DOI: /j.ophtha
Copyright © 2015 American Academy of Ophthalmology Terms and Conditions

2. Figure 1
Spectrum of serous retinopathy associated with binimetinib treatment. A, Fundus photograph of a 65-year-old patient with metastatic cutaneous melanoma (CM) who developed a central yellowish lesion in the fovea. B, On infrared reflectance (IRR) imaging, a lesion of approximately 1/3 disc diameter was found, showing a hyperreflective center, surrounded by a hyporeflective zone. C, On optical coherence tomography (OCT) a dome-shaped accumulation of subretinal fluid (SRF) was detected. D-F, Foveal and extrafoveal yellowish lesions with a vitelliform aspect developing 12 days after the start of binimetinib treatment in a 67-year-old patient with metastatic CM. The IRR imaging showed a foveal lesion of approximately 1 optic disc diameter, again showing a hyperreflective center, surrounded by a hyporeflective zone, and multiple smaller lesions scattered throughout the posterior pole with similar reflectance characteristics. These lesions were dome-shaped on OCT (F). G and H, Multifocal serous retinopathy with smaller round to oval lesions and larger, more indistinct and irregular lesions on IRR imaging (G), occurring 16 days after the start of binimetinib in a 64-year-old patient with metastatic CM. Lesions were present only outside the fovea. On OCT (scanning plane depicted with light-green line in G), the smaller round/oval lesions corresponded to a dome-shaped accumulation of SRF (H, black arrow), and the larger irregular lesions corresponded to a shallow neuroretinal detachment (H, white arrow). The space between the small and shallow neuroretinal detachments and retinal pigment epithelium was filled mainly with hyperreflective material on OCT, presumably corresponding to accumulation of shed photoreceptor outer segment debris. I and J, Multiple lesions on IRR imaging (I) and the corresponding fundus autofluorescence (FAF) image (J) in binimetinib-associated serous retinopathy. On FAF, the lesions corresponded to mildly decreased autofluorescence, in some lesions with a border of faintly increased autofluorescence.
Ophthalmology  , DOI: ( /j.ophtha )
Copyright © 2015 American Academy of Ophthalmology Terms and Conditions

3. Figure 2
Multimodal imaging illustrating the clinical course of serous retinopathy associated with binimetinib treatment. A–C, Multifocal, variably sized serous neuroretinal detachments on red-free fundus photography (A) and infrared reflectance (IRR) imaging (B) in a 64-year-old patient with metastatic cutaneous melanoma (CM) treated with binimetinib. Bilateral mild intraretinal fluid accumulation and a dome-shaped serous neuroretinal detachment with subretinal fluid (SRF) accumulation were seen on optical coherence tomography (OCT) (C). The intraretinal fluid appeared 20 days after the start of binimetinib and disappeared in 12 days. The binimetinib dose was tapered 7 days after appearance of the intraretinal fluid. Resolution of the intraretinal fluid occurred faster than the resolution of the subfoveal SRF, which was still present at ophthalmological follow-up 11 weeks later. D and H, A 65-year-old patient with metastatic CM with yellowish, foveal, and small, round, and oval vitelliform extrafoveal lesions on fundus photography (D), corresponding to hyporeflective lesions with a moderately hyperreflective center on IRR imaging (E). On OCT (light-green line in E indicating scanning plane), the foveal lesion corresponded to a focal serous neuroretinal detachment (F). On fluorescein angiography (FA), lesions showed hardly any fluorescence changes in the early phase (G), whereas the smaller temporal lesions showed modest fluorescein staining in the late phase of the angiogram, and the foveal lesions remained mostly hypofluorescent (H). No FA abnormalities were present after resolution of the serous SRF. I–U, Evolution of binimetinib-associated serous retinopathy in a 45-year-old patient with metastatic CM. At the baseline examination before the start of binimetinib treatment, the OCT scan showed an entirely normal macular structure (M). Within 1 day after the start of binimetinib treatment (45 mg twice daily), the patient developed bilateral small, round, and relatively well-demarcated foveal lesions without evidence of extrafoveal lesions (I). These lesions corresponded to a shallow neuroretinal detachment on OCT (N). Binimetinib was stopped to assess the effect of treatment discontinuation on the retinopathy. Five days after the discontinuation of binimetinib, SRF resolution was seen on OCT (O). Study medication was restarted at a lower dose (30 mg twice daily), and a shallow unilateral serous neuroretinal detachment reoccurred between 3 (P) and 4 days (Q) after the restart. In addition, small, round, and oval extrafoveal lesions (J), which were dome-shaped on OCT (K), gradually developed in these 5 days after restarting binimetinib. Fundus autofluorescence of the foveal lesion showed no obvious abnormalities in the fovea and only minor fundus autofluorescence (FAF) changes corresponding to the focal lesions superior in the macula (L). Despite the fact that binimetinib treatment was continued after this reoccurrence of lesions, the foveal SRF resolved 2 days after the restart of binimetinib (R), and this resolution of the lesion persisted 6 (S), 21 (T), and 43 days later (U). Resolution of the extrafoveal lesions occurred between 6 and 21 days later.
Ophthalmology  , DOI: ( /j.ophtha )
Copyright © 2015 American Academy of Ophthalmology Terms and Conditions

4. Figure 3
Functional findings in serous retinopathy associated with binimetinib treatment. This 67-year-old asymptomatic patient with metastatic uveal melanoma, who previously received proton beam radiation therapy in the left eye and was currently treated with binimetinib and sotrastaurin, showed mildly decreased retinal sensitivity (A) on microperimetry in the area of neuroretinal detachment (B). At this moment, the patient had no visual symptoms. An electro-oculogram was made 1 week earlier, when the patient reported symptoms of blurred vision, showing Arden ratios of 1.68 (right eye) and 1.28 (left eye). However, the low Arden ratio in the left eye may be partly due to the previous proton beam radiation therapy.
Ophthalmology  , DOI: ( /j.ophtha )
Copyright © 2015 American Academy of Ophthalmology Terms and Conditions