e686
8 Resolved
8 Resolved
5
20/20; 20/20 Yes
Yes
20/20
20/100; 20/63
20/30; 20/30 Blurry vision, red eyes and watering Both eyes 480/12
Left eye 720/12 45
60
Male
Male
12
Both eyes 960/12 29 73
7
20/50
20/200; 20/400
Anterior, Posterior synechiae Anterior, Posterior synechiae Anterior, Posterior synechiae
Yes
Topical steroids + intravitreal dexamethasone implant Topical steroids + oral prednisone Topical steroids+ sub-Tenon triamcinolone
Resolved
2 Resolved 20/15; 20/20 Topical steroids No Anterior 20/20; 20/20
Blurry vision and red eyes Blurry vision and mild pain Blurry vision
Symptoms Eye
Both eyes 720/12 4
Outcome Visual acuity (last visit) Treatment Cystoid macular oedema Type of uveitis and clinical findings
Male
doi: 10.1111/aos.12678
42
Department of Ophthalmology, BioCruces Health Research Institute, Cruces University Hospital, University of the Basque Country, Barakaldo, Spain; 2 Institut Clınic d’Oftalmologia, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain
Male
1
Age
Alex Fonollosa,1 Marina Mesquida2 and Alfredo Adan2
Gender
Uveitic macular oedema after treatment with vemurafenib
Visual acuity on admission
Correspondence: Dr. Kemal O¨rnek, MD Kırıkkale University School of Medicine Yahsßihan Kırıkkale 71450 Turkey Tel: +90-318-3335010 Fax: +90-318-2240786 Email: [email protected]
Dose of vemurafenib (mg/h)
Adhi M, Brewer E, Waheed NK & Duker JS (2013): Analysis of morphological features and vascular layers of choroid in diabetic retinopathy using spectral-domain optical coherence tomography. JAMA Ophthalmol 131: 1267–1274. Johnson MA, Lutty GA, McLeod DS et al. (2005): Ocular structure and function in an aged monkey with spontaneous diabetes mellitus. Exp Eye Res 80: 37–42. Kim JT, Lee DH, Joe SG, Kim JG & Yoon YH (2013): Changes in choroidal thickness in relation to the severity of retinopathy and macular edema in type 2 diabetic patients. Invest Ophthalmol Vis Sci 54: 3378–3384. Marneros AG, Fan J, Yokoyama Y, Gerber HP, Ferrara N, Crouch RK & Olsen BR (2005): Vascular endothelial growth factor expression in the retinal pigment epithelium is essential for choriocapillaris development and visual function. Am J Pathol 167: 1451– 1459. Saint-Geniez M1, Maldonado AE & D’Amore PA (2006): VEGF expression and receptor activation in the choroid during development and in the adult. Invest Ophthalmol Vis Sci 47: 3135–3142.
V
Duration of vemurafenib therapy (months)
References
Editor, emurafenib is a potent kinase inhibitor approved for the treatment of metastatic cutaneous melanoma. It inhibits the serine/threonine protein kinase B-raf encoded by a gene that carries a specific mutation, the so-called V600 mutation. Survival in patients with BRAF V600-mutant metastatic cutaneous melanoma is dramatically better with this drug than with classic chemotherapy (Sosman et al. 2012). However, mild uveitis was described as an adverse effect in 4% of cases in pivotal clinical trials of vemurafenib (Choe et al. 2014). We report our experience in the management of uveitic cystoid macular oedema (CME) secondary to vemurafenib use. Since October 2013, we have managed four cases of uveitis secondary to vemurafenib therapy at two general uveitis referral centres, three of the patients presenting cystoid macular oedema (CME). All the patients were male with a median age of 52.5 [42–73] years, and median initial visual acuity was 20/30 [20/20–20/400]. The dosage of vemurafenib at onset of uveitis was 960 mg twice a day in one patient, 720 mg twice a day in two patients and 480 mg twice a day in one patient. Median duration of vemurafenib therapy before uveitis onset was 9.5 [4–29] months. Uveitis was bilateral in three of the four patients and was classified as non-granulomatous and anterior in all cases. Three patients were found to have CME on optical coherence tomography. In these cases, treatment consisted of topical steroids, together with bilateral intravitreal injection of dexamethasone implants in one, oral prednisone in another and bilateral sub-Tenon’s injection of triamcinolone in the last case. Intraocular inflammation and CME resolved in all three cases. Median VA at the last follow-up visit was 20/20 [20/15–20/100]. Vemurafenib was stopped and reintroduced after resolution of the uveitis in all patients. Median follow-up after reintroduction of vemurafenib was 6.5 [2– 8] months, and uveitis has not been observed to recur after reintroduction. Table 1 shows clinical features and outcomes of all four patients. Until recently, treatment options for metastatic melanoma were almost nonexistent. This situation has dramatically changed with the introduction of
Table 1. Clinical characteristics and outcomes of patients.
transiently, particularly in the peripapillary area, following IVB in the treated eyes of patients with DMO.
Follow-up (months)
Acta Ophthalmologica 2015
Acta Ophthalmologica 2015
vemurafenib and other drugs. In addition to the mild uveitis described as an adverse effect (in 4% of cases) in pivotal clinical trials of vemurafenib (Choe et al. 2014), two recent publications have shown that CME may also develop in these patients. In a recent case series, this latter complication led to vemurafenib discontinuation (Guedj et al. 2014). In another reported case, CME was treated with sub-Tenon’s injections of triamcinolone after stopping vemurafenib (Agemy et al. 2014). In our three patients, CME responded favourably to steroids (oral, periocular or intravitreal). Moreover, vemurafenib was able to be reintroduced without recurrence of intraocular inflammation. We suggest CME may be effectively managed with standard treatment and temporary discontinuation of vemurafenib. This strategy may allow patients with cutaneous metastatic melanoma to keep on receiving this drug, which has shown great efficacy, dramatically improving survival.
References Agemy SA, Metha AN, Pachydaki SI, Tewari A et al. (2014): Bilateral panuveitis in a patient on vemurafenib BRAF inhibitor therapy for stage IV melanoma. Eur J Ophthalmol 24: 629–632. Choe CH, McArthur GA, Caro I, Kempen JH & Amaravadi RK et al. (2014): Ocular toxicity in BRAF mutant cutaneous melanoma patients treated with vemurafenib. Am J Ophthalmol 158: 831–837. Guedj M, Queant A, Funck-Brentano E et al. (2014): Uveitis in patients with latestage cutaneous melanoma treated with vemurafenib. JAMA Ophthalmol 132: 1421–1425. Sosman JA, Kim KB, Schuchter L et al. (2012): Survival in BRAF-V600 mutant advanced melanoma treated with vemurafenib. N Engl J Med 366: 707–714.
Correspondence: Alex Fonollosa, PhD Department of Ophthalmology Cruces University Hospital plaza de Cruces s/n Cruces-Barakaldo cp 48903, Vizcaya Spain Tel: +34 646844328 Fax: +34 946006456 Email: [email protected]
Low prevalence of anterior vitreous detachment in eyes with pseudophakic retinal detachment indicates strong vitreoretinal adhesions Christine B. Scha¨ffer, Eva M. Po¨schl, Gernot Steinwender, Andreas Wedrich and Domagoj Ivastinovic Department of Ophthalmology, Medical University Graz, Graz, Austria doi: 10.1111/aos.12673
Editor, hegmatogenous retinal detachment (RRD) occurs more frequently in pseudophakic eyes than in phakic eyes (Coppe & Lapucci 2008). This phenomenon is presumably based on the acceleration of posterior vitreous detachment (PVD) after cataract surgery secondary to postoperative vitreous changes (Ueno et al. 1987; Neal et al. 2005; Ivastinovic et al. 2012). The etiological retinal tears commonly develop in areas with strong vitreoretinal adhesions which need to be released during vitrectomy. According to our personal experience, pseudophakic eyes with RRD show a firm adherence of the anterior hyaloid to the posterior lens capsule. To objectify our personal observation, we assessed the anterior vitreous with optical coherence tomography (OCT) (Figs 1 and 2). The contribution of anterior vitreous in the development of RRD remains unknown, however. The aim of our
R
study was to compare the prevalence of anterior vitreous detachment (AVD) in pseudophakic eyes with RRD and without RRD serving as controls. This prospective controlled study was approved by the ethics committee of the Medical University Graz, Austria. We recruited patients at the Department of Ophthalmology, Medical University Graz, between June 2013 and September 2014. Pseudophakic patients undergoing vitrectomy for RRD were enrolled in the study group, and pseudophakic patients undergoing cataract surgery on their fellow eye were enrolled in the control group. Exclusion criteria were previous surgeries including scleral buckle or vitrectomy, previously performed Nd: YAG capsulotomy, intra-operative capsule rupture or a history of ocular trauma. The anterior vitreous was assessed with High-Definition-OCT (CirrusTM; Carl Zeiss Meditec, Jena, Germany) using the anterior segment cube 512 9 128 adjustment. All patients were examined after full pupil dilation with mydriatic drops. Particular attention was paid to the interface between the anterior vitreous cortex and the posterior lens capsule. In the control group, the status of the posterior hyaloid was additionally assessed using the macular cube 512 9 128 adjustment. Descriptive statistics were presented as mean standard deviation. Normal distribution was assessed with the Kolmogorov–Smirnov test. The appropriate statistical method was depicted where suitable. The threshold for statistical significance was defined as p < 0.05. Overall, 55 eyes of 55 patients were enrolled in the study. The study group included 24 patients (3 female; 21 male);
Fig. 1. Schematic illustration of the anterior segment. The arrowheads indicate an attachment of the anterior hyaloid to the posterior lens capsule. AVC = anterior vitreous cortex, WL = Wieger0 s ligament, BS = Berger0 s space, VB = vitreous base.
e687
8 Resolved
8 Resolved
5
20/20; 20/20 Yes
Yes
20/20
20/100; 20/63
20/30; 20/30 Blurry vision, red eyes and watering Both eyes 480/12
Left eye 720/12 45
60
Male
Male
12
Both eyes 960/12 29 73
7
20/50
20/200; 20/400
Anterior, Posterior synechiae Anterior, Posterior synechiae Anterior, Posterior synechiae
Yes
Topical steroids + intravitreal dexamethasone implant Topical steroids + oral prednisone Topical steroids+ sub-Tenon triamcinolone
Resolved
2 Resolved 20/15; 20/20 Topical steroids No Anterior 20/20; 20/20
Blurry vision and red eyes Blurry vision and mild pain Blurry vision
Symptoms Eye
Both eyes 720/12 4
Outcome Visual acuity (last visit) Treatment Cystoid macular oedema Type of uveitis and clinical findings
Male
doi: 10.1111/aos.12678
42
Department of Ophthalmology, BioCruces Health Research Institute, Cruces University Hospital, University of the Basque Country, Barakaldo, Spain; 2 Institut Clınic d’Oftalmologia, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain
Male
1
Age
Alex Fonollosa,1 Marina Mesquida2 and Alfredo Adan2
Gender
Uveitic macular oedema after treatment with vemurafenib
Visual acuity on admission
Correspondence: Dr. Kemal O¨rnek, MD Kırıkkale University School of Medicine Yahsßihan Kırıkkale 71450 Turkey Tel: +90-318-3335010 Fax: +90-318-2240786 Email: [email protected]
Dose of vemurafenib (mg/h)
Adhi M, Brewer E, Waheed NK & Duker JS (2013): Analysis of morphological features and vascular layers of choroid in diabetic retinopathy using spectral-domain optical coherence tomography. JAMA Ophthalmol 131: 1267–1274. Johnson MA, Lutty GA, McLeod DS et al. (2005): Ocular structure and function in an aged monkey with spontaneous diabetes mellitus. Exp Eye Res 80: 37–42. Kim JT, Lee DH, Joe SG, Kim JG & Yoon YH (2013): Changes in choroidal thickness in relation to the severity of retinopathy and macular edema in type 2 diabetic patients. Invest Ophthalmol Vis Sci 54: 3378–3384. Marneros AG, Fan J, Yokoyama Y, Gerber HP, Ferrara N, Crouch RK & Olsen BR (2005): Vascular endothelial growth factor expression in the retinal pigment epithelium is essential for choriocapillaris development and visual function. Am J Pathol 167: 1451– 1459. Saint-Geniez M1, Maldonado AE & D’Amore PA (2006): VEGF expression and receptor activation in the choroid during development and in the adult. Invest Ophthalmol Vis Sci 47: 3135–3142.
V
Duration of vemurafenib therapy (months)
References
Editor, emurafenib is a potent kinase inhibitor approved for the treatment of metastatic cutaneous melanoma. It inhibits the serine/threonine protein kinase B-raf encoded by a gene that carries a specific mutation, the so-called V600 mutation. Survival in patients with BRAF V600-mutant metastatic cutaneous melanoma is dramatically better with this drug than with classic chemotherapy (Sosman et al. 2012). However, mild uveitis was described as an adverse effect in 4% of cases in pivotal clinical trials of vemurafenib (Choe et al. 2014). We report our experience in the management of uveitic cystoid macular oedema (CME) secondary to vemurafenib use. Since October 2013, we have managed four cases of uveitis secondary to vemurafenib therapy at two general uveitis referral centres, three of the patients presenting cystoid macular oedema (CME). All the patients were male with a median age of 52.5 [42–73] years, and median initial visual acuity was 20/30 [20/20–20/400]. The dosage of vemurafenib at onset of uveitis was 960 mg twice a day in one patient, 720 mg twice a day in two patients and 480 mg twice a day in one patient. Median duration of vemurafenib therapy before uveitis onset was 9.5 [4–29] months. Uveitis was bilateral in three of the four patients and was classified as non-granulomatous and anterior in all cases. Three patients were found to have CME on optical coherence tomography. In these cases, treatment consisted of topical steroids, together with bilateral intravitreal injection of dexamethasone implants in one, oral prednisone in another and bilateral sub-Tenon’s injection of triamcinolone in the last case. Intraocular inflammation and CME resolved in all three cases. Median VA at the last follow-up visit was 20/20 [20/15–20/100]. Vemurafenib was stopped and reintroduced after resolution of the uveitis in all patients. Median follow-up after reintroduction of vemurafenib was 6.5 [2– 8] months, and uveitis has not been observed to recur after reintroduction. Table 1 shows clinical features and outcomes of all four patients. Until recently, treatment options for metastatic melanoma were almost nonexistent. This situation has dramatically changed with the introduction of
Table 1. Clinical characteristics and outcomes of patients.
transiently, particularly in the peripapillary area, following IVB in the treated eyes of patients with DMO.
Follow-up (months)
Acta Ophthalmologica 2015
Acta Ophthalmologica 2015
vemurafenib and other drugs. In addition to the mild uveitis described as an adverse effect (in 4% of cases) in pivotal clinical trials of vemurafenib (Choe et al. 2014), two recent publications have shown that CME may also develop in these patients. In a recent case series, this latter complication led to vemurafenib discontinuation (Guedj et al. 2014). In another reported case, CME was treated with sub-Tenon’s injections of triamcinolone after stopping vemurafenib (Agemy et al. 2014). In our three patients, CME responded favourably to steroids (oral, periocular or intravitreal). Moreover, vemurafenib was able to be reintroduced without recurrence of intraocular inflammation. We suggest CME may be effectively managed with standard treatment and temporary discontinuation of vemurafenib. This strategy may allow patients with cutaneous metastatic melanoma to keep on receiving this drug, which has shown great efficacy, dramatically improving survival.
References Agemy SA, Metha AN, Pachydaki SI, Tewari A et al. (2014): Bilateral panuveitis in a patient on vemurafenib BRAF inhibitor therapy for stage IV melanoma. Eur J Ophthalmol 24: 629–632. Choe CH, McArthur GA, Caro I, Kempen JH & Amaravadi RK et al. (2014): Ocular toxicity in BRAF mutant cutaneous melanoma patients treated with vemurafenib. Am J Ophthalmol 158: 831–837. Guedj M, Queant A, Funck-Brentano E et al. (2014): Uveitis in patients with latestage cutaneous melanoma treated with vemurafenib. JAMA Ophthalmol 132: 1421–1425. Sosman JA, Kim KB, Schuchter L et al. (2012): Survival in BRAF-V600 mutant advanced melanoma treated with vemurafenib. N Engl J Med 366: 707–714.
Correspondence: Alex Fonollosa, PhD Department of Ophthalmology Cruces University Hospital plaza de Cruces s/n Cruces-Barakaldo cp 48903, Vizcaya Spain Tel: +34 646844328 Fax: +34 946006456 Email: [email protected]
Low prevalence of anterior vitreous detachment in eyes with pseudophakic retinal detachment indicates strong vitreoretinal adhesions Christine B. Scha¨ffer, Eva M. Po¨schl, Gernot Steinwender, Andreas Wedrich and Domagoj Ivastinovic Department of Ophthalmology, Medical University Graz, Graz, Austria doi: 10.1111/aos.12673
Editor, hegmatogenous retinal detachment (RRD) occurs more frequently in pseudophakic eyes than in phakic eyes (Coppe & Lapucci 2008). This phenomenon is presumably based on the acceleration of posterior vitreous detachment (PVD) after cataract surgery secondary to postoperative vitreous changes (Ueno et al. 1987; Neal et al. 2005; Ivastinovic et al. 2012). The etiological retinal tears commonly develop in areas with strong vitreoretinal adhesions which need to be released during vitrectomy. According to our personal experience, pseudophakic eyes with RRD show a firm adherence of the anterior hyaloid to the posterior lens capsule. To objectify our personal observation, we assessed the anterior vitreous with optical coherence tomography (OCT) (Figs 1 and 2). The contribution of anterior vitreous in the development of RRD remains unknown, however. The aim of our
R
study was to compare the prevalence of anterior vitreous detachment (AVD) in pseudophakic eyes with RRD and without RRD serving as controls. This prospective controlled study was approved by the ethics committee of the Medical University Graz, Austria. We recruited patients at the Department of Ophthalmology, Medical University Graz, between June 2013 and September 2014. Pseudophakic patients undergoing vitrectomy for RRD were enrolled in the study group, and pseudophakic patients undergoing cataract surgery on their fellow eye were enrolled in the control group. Exclusion criteria were previous surgeries including scleral buckle or vitrectomy, previously performed Nd: YAG capsulotomy, intra-operative capsule rupture or a history of ocular trauma. The anterior vitreous was assessed with High-Definition-OCT (CirrusTM; Carl Zeiss Meditec, Jena, Germany) using the anterior segment cube 512 9 128 adjustment. All patients were examined after full pupil dilation with mydriatic drops. Particular attention was paid to the interface between the anterior vitreous cortex and the posterior lens capsule. In the control group, the status of the posterior hyaloid was additionally assessed using the macular cube 512 9 128 adjustment. Descriptive statistics were presented as mean standard deviation. Normal distribution was assessed with the Kolmogorov–Smirnov test. The appropriate statistical method was depicted where suitable. The threshold for statistical significance was defined as p < 0.05. Overall, 55 eyes of 55 patients were enrolled in the study. The study group included 24 patients (3 female; 21 male);
Fig. 1. Schematic illustration of the anterior segment. The arrowheads indicate an attachment of the anterior hyaloid to the posterior lens capsule. AVC = anterior vitreous cortex, WL = Wieger0 s ligament, BS = Berger0 s space, VB = vitreous base.
e687
