Acta Ophthalmologica 2014
1999). The chorioretinal complex may be heated up by the light absorption in the melanosomes of the retinal pigment epithelium (RPE) and the choroid (Parver 1991). Therefore, an increase in the environmental light intensity increases the temperature of the macula which is at the focal point of the irradiating lights into the eye. If the focal heat is high enough to induce severe choroidal vasodilation but not to burn the tissue, and if the rate of the heat accumulation is higher than the rate of adaptation of choroidal circulation to bright lights, it may result in a focal serous leakage from the dilated choroidal vessels. In conclusion, CSCR may result from a response of choroidal vessels to an acute increase in the environmental light intensity. The increase in the light intensity may increase the choroidal temperature at the focal point of the irradiating lights into the eye. The resultant focal heat may induce local changes in the choroidal vessels leading to a focal leakage from the choroidal vessels and CSCR. However, this hypothesis should be experimentally tested. Future clinical researches should consider the history of acute increase in the intensity of lights to which patients with CSCR are exposed. Assessment of the relationship of increases in total time spent outdoors with prevalence of CSCR may be helpful. If the hypothesis is proved to be correct, it may be helpful to design more efficient strategies to prevent and manage CSCR.
References Parver LM (1991): Temperature modulating action of choroidal blood flow. Eye 5(Pt. 2): 181–185. Parver LM, Auker C & Carpenter DO (1980): Choroidal blood flow as a heat dissipating mechanism in the macula. Am J Ophthalmol 89: 641–646. Parver LM, Auker CR & Carpenter DO (1983): Choroidal blood flow. III. Reflexive control in human eyes. Arch Ophthalmol 101: 1604–1606. Shih YF, Fitzgerald ME, Cuthbertson SL & Reiner A (1999): Influence of ophthalmic nerve fibers on choroidal blood flow and myopic eye growth in chicks. Exp Eye Res 69: 9–20. Yang L, Jonas JB & Wei W (2013): Choroidal vessel diameter in central serous chorioretinopathy. Acta Ophthalmol 91: e358–e362.
Correspondence: Amir Norouzpour, MD Eye Research Center Khatam-Al-Anbia Eye Hospital Mashhad University of Medical Sciences (MUMS) Mashhad, Iran Tel/Fax: +98-511-7281400 Emails: [email protected]; [email protected]
Central serous chorioretinopathy and bright light: authors reply Lihong Yang,1 Jost B. Jonas2,3 and Wenbin Wei1 1
Beijing Ophthalmology &Visual Sciences Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China; 2Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China; 3Department of Ophthalmology, Universit€ atsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
subsides after several months, although the environmental light exposure may have been unchanged. One would also expect to find CSC more often in patients with outdoor professions. These and other questions may be explored in further clinical research as also suggested by Dr Norouzpour.
Reference Norouzpour A (2014): Central serious chorioretinopathy and bright light. Acta Ophthalmol. In press. Yang L, Jonas JB & Wei W (2013): Choroidal vessel diameter in central serous chorioretinopathy. Acta Ophthalmol 91: e358– e362.
Correspondence: Wenbin Wei, MD Beijing Ophthalmology & Visual Sciences Key Lab Beijing Tongren Eye Center Beijing Tongren Hospital Capital Medical University No.1, Dong Jiao Min Xiang Dong Cheng District 100730 Beijing, China Tel: + 86 10 5826 9152 Fax: + 86 10 5612 9156 Email: [email protected]
doi: 10.1111/aos.12477
Editor, he authors would like to thank Dr Norouzpour for his interest in our study (Yang et al. 2013). In his letter, he postulates that the subfoveal choroidal vascular dilatation in eyes with central serous chorioretinopathy (CSC) may be due to an increase in choroidal temperature, caused by an increase in the environmental light intensity (Norouzpour 2014). If the subfoveal temperature exceeds a critical point, focal serous leakage from the dilated choroidal vessels may occur. This interesting hypothesis needs further exploration. If the hypothesis is valid, one may argue that CSC should occur more frequently in summer than in winter, and that it should be more common within the same ethnic group in geographical regions with higher sun intensity. Another question would be why CSC usually
T
Topical dexamethasone– cyclodextrin microparticle eye drops for uveitic macular oedema Susanne Krag and Anders Hessellund Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark doi: 10.1111/aos.12560
Editor, ystoid macular oedema (CME) is the main cause of visual loss in patients with uveitis (Rothova 2007). The mainstay of treatment of uveitic CME is corticosteroids and to be effective, steroid needs to be given periocularly, intravitreally or systemically. Topical steroid generally is of little benefit for the treatment of posterior segment diseases. Dexamethasone eye drops containing c-cyclodextrin-
C
e689
Acta Ophthalmologica 2014
based nanoparticles, however, have recently been shown to be effectively delivered to the posterior part of the eye to treat diabetic CME (Loftsson & Stefansson 2002; Loftsson et al. 2007; Tanito et al. 2011). Therefore, it seems tempting to examine the effect of this dexamethasone eye drop formulation for the treatment of uveitis with posterior manifestations. We have treated three patients with uveitic CME with 1.5% dexamethasone–cyclodextrin ophthalmic solution (Oculis ehf., Reykjavik, Iceland) after obtaining informed consent from each patient. A 54-year-old female with bilateral, chronic, idiopathic intermediate uveitis and CME. Left eye was previously vitrectomized. Visual acuity was reduced to 0.4 (in decimals) on both eyes. She had pronounced CME and slight vitritis (+1) in both eyes. The CME and vitritis resolved on treatment with systemic prednisone in high dose and visual acuity increased to 0.63 in both eyes. CME on the left eye, however, recurred 3 months after tapering prednisone (Fig. 1A), and visual acuity dropped down to 0.5. The patient was then treated with 1.5% dexamethasone–cyclodextrin ophthalmic solution four times daily for 1 month in the left eye. Visual acuity increased to 0.63 and the CME resolved (Fig. 1B). As dexamethasone– cyclodextrin eye drops are not available in Denmark, she then continued treatment with commercial dexamethasone eye drops, Maxidex â (Dexamethasone 0.1%; Alcon Inc, Fort Worth, TX, USA) 4 times daily in the left eye. After 1 month, the CME in the left eye had recurred (Fig. 1C), and she was subsequently treated with periocular triamcinolone acetonide and systemic prednisone in a low dose. A 84-year-old woman with bilateral vitritis and CME. Vitritis resolved after initating systemical treatment with mycophenolate mofetil. CME was persistent in both eyes (foveal thickness 357/ 332 lm). Visual acuity was 0.5 in both eyes. Right eye was treated with dexamethasone–cyclodextrin eye drops two drops four times daily tapered to one drop three times daily after 3 weeks. Left eye was treated with an intravitreal dexamethasone implant (Ozurdex; Allergan, Inc., Irvine, CA, USA). After 6 weeks of treatment, visual
e690
(A)
(B)
(C) Fig. 1. Optical Coherence Tomography images of the 54-year-old female with bilateral uveitic CME centred in the fovea (OCT; Cirrus, Carl Zeiss Meditec, Jena, Germany) before treatment with 1.5% dexamethasone–cyclodextrin nanoparticle eye drops (foveal thickness 404 lm) (A), after 1 month of treatment with the dexamethasone–cyclodextrin solution (foveal thickness 314 lm) (B) and subsequently after 1 month of treatment with Maxidex â (0.1% dexamethasone eye drops) (foveal thickness 390 lm) (C).
acuity was 0.8 in the right eye and 0.63 in the left eye, and the CME had resolved in both eyes (foveal thickness 315/317 lm). A 47-year-old woman with chronic, bilateral, posterior uveitis and CME. She was treated with Ozurdex in both eyes, but the CME recurred after 3 months. The Ozurdex implantation was repeated on the left eye. The right eye was treated with dexamethasone–cyclodextrin eye drops one drop six times daily for 1 week and then four times daily for 1 week. After 2 weeks of treatment, the CME in the right eye was increased further, and the eye received a new Ozurdex implant.
The present cases indicate that topical dexamethasone–cyclodextrin nanoparticle eye drops may be effective for the treatment of uveitic CME in some patients. In the first two cases, the CME was resolved after 1 month of treatment with this topical steroid formulation and recurred 1 month after treatment with conventional steroid eye drops. It therefore seems worth to explore the potential of dexamethasone–cyclodextrin nanoparticle eye drops for the treatment of uveitis with posterior manifestations as an alternative to periocular, intravitreal and systemic treatment with steroid. Periocular and intravitreal steroid carry a potential risk of ocular complications, and treatment with systemic steroid involves a considerable risk of serious systemic side-effects. Moreover, in children, the possibility of topical steroid treatment for uveitis with posterior manifestations would be of great benefit as treatment with periocular and intravitreal steroid in these patients requires a general anaesthetic prior to administration.
References Loftsson T & Stefansson E (2002): Cyclodextrins in eye drops formulations: enhanced topical delivery of corticosteroid to the eye. Acta Ophthalmol Scand 80: 144– 150. Loftsson T, Hreinsdottir D & Stefansson E (2007): Cyclodextrin microparticles for drug delivery to the posterior segment of the eye: aqueous dexamethasone eye drops. J Pharm Pharmacol 59: 629–635. Rothova A (2007): Inflammatory cystoid macular edema. Curr Opin Ophthalmol 18: 487–492. Tanito M, Hara K, Takai Y et al. (2011): Topical dexamethasone-cyclodextrin microparticle eye drops for diabetic macular edema. Invest Ophthalmol Vis Sci 52: 7944–7948.
Correspondence: Susanne Krag Department of Ophthalmology Aarhus University Hospital Nørrebrogade 44 8000 Aarhus Denmark Tel: +45 78 46 32 34 Fax: +45 78 46 32 26 Email: [email protected]
1999). The chorioretinal complex may be heated up by the light absorption in the melanosomes of the retinal pigment epithelium (RPE) and the choroid (Parver 1991). Therefore, an increase in the environmental light intensity increases the temperature of the macula which is at the focal point of the irradiating lights into the eye. If the focal heat is high enough to induce severe choroidal vasodilation but not to burn the tissue, and if the rate of the heat accumulation is higher than the rate of adaptation of choroidal circulation to bright lights, it may result in a focal serous leakage from the dilated choroidal vessels. In conclusion, CSCR may result from a response of choroidal vessels to an acute increase in the environmental light intensity. The increase in the light intensity may increase the choroidal temperature at the focal point of the irradiating lights into the eye. The resultant focal heat may induce local changes in the choroidal vessels leading to a focal leakage from the choroidal vessels and CSCR. However, this hypothesis should be experimentally tested. Future clinical researches should consider the history of acute increase in the intensity of lights to which patients with CSCR are exposed. Assessment of the relationship of increases in total time spent outdoors with prevalence of CSCR may be helpful. If the hypothesis is proved to be correct, it may be helpful to design more efficient strategies to prevent and manage CSCR.
References Parver LM (1991): Temperature modulating action of choroidal blood flow. Eye 5(Pt. 2): 181–185. Parver LM, Auker C & Carpenter DO (1980): Choroidal blood flow as a heat dissipating mechanism in the macula. Am J Ophthalmol 89: 641–646. Parver LM, Auker CR & Carpenter DO (1983): Choroidal blood flow. III. Reflexive control in human eyes. Arch Ophthalmol 101: 1604–1606. Shih YF, Fitzgerald ME, Cuthbertson SL & Reiner A (1999): Influence of ophthalmic nerve fibers on choroidal blood flow and myopic eye growth in chicks. Exp Eye Res 69: 9–20. Yang L, Jonas JB & Wei W (2013): Choroidal vessel diameter in central serous chorioretinopathy. Acta Ophthalmol 91: e358–e362.
Correspondence: Amir Norouzpour, MD Eye Research Center Khatam-Al-Anbia Eye Hospital Mashhad University of Medical Sciences (MUMS) Mashhad, Iran Tel/Fax: +98-511-7281400 Emails: [email protected]; [email protected]
Central serous chorioretinopathy and bright light: authors reply Lihong Yang,1 Jost B. Jonas2,3 and Wenbin Wei1 1
Beijing Ophthalmology &Visual Sciences Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China; 2Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China; 3Department of Ophthalmology, Universit€ atsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
subsides after several months, although the environmental light exposure may have been unchanged. One would also expect to find CSC more often in patients with outdoor professions. These and other questions may be explored in further clinical research as also suggested by Dr Norouzpour.
Reference Norouzpour A (2014): Central serious chorioretinopathy and bright light. Acta Ophthalmol. In press. Yang L, Jonas JB & Wei W (2013): Choroidal vessel diameter in central serous chorioretinopathy. Acta Ophthalmol 91: e358– e362.
Correspondence: Wenbin Wei, MD Beijing Ophthalmology & Visual Sciences Key Lab Beijing Tongren Eye Center Beijing Tongren Hospital Capital Medical University No.1, Dong Jiao Min Xiang Dong Cheng District 100730 Beijing, China Tel: + 86 10 5826 9152 Fax: + 86 10 5612 9156 Email: [email protected]
doi: 10.1111/aos.12477
Editor, he authors would like to thank Dr Norouzpour for his interest in our study (Yang et al. 2013). In his letter, he postulates that the subfoveal choroidal vascular dilatation in eyes with central serous chorioretinopathy (CSC) may be due to an increase in choroidal temperature, caused by an increase in the environmental light intensity (Norouzpour 2014). If the subfoveal temperature exceeds a critical point, focal serous leakage from the dilated choroidal vessels may occur. This interesting hypothesis needs further exploration. If the hypothesis is valid, one may argue that CSC should occur more frequently in summer than in winter, and that it should be more common within the same ethnic group in geographical regions with higher sun intensity. Another question would be why CSC usually
T
Topical dexamethasone– cyclodextrin microparticle eye drops for uveitic macular oedema Susanne Krag and Anders Hessellund Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark doi: 10.1111/aos.12560
Editor, ystoid macular oedema (CME) is the main cause of visual loss in patients with uveitis (Rothova 2007). The mainstay of treatment of uveitic CME is corticosteroids and to be effective, steroid needs to be given periocularly, intravitreally or systemically. Topical steroid generally is of little benefit for the treatment of posterior segment diseases. Dexamethasone eye drops containing c-cyclodextrin-
C
e689
Acta Ophthalmologica 2014
based nanoparticles, however, have recently been shown to be effectively delivered to the posterior part of the eye to treat diabetic CME (Loftsson & Stefansson 2002; Loftsson et al. 2007; Tanito et al. 2011). Therefore, it seems tempting to examine the effect of this dexamethasone eye drop formulation for the treatment of uveitis with posterior manifestations. We have treated three patients with uveitic CME with 1.5% dexamethasone–cyclodextrin ophthalmic solution (Oculis ehf., Reykjavik, Iceland) after obtaining informed consent from each patient. A 54-year-old female with bilateral, chronic, idiopathic intermediate uveitis and CME. Left eye was previously vitrectomized. Visual acuity was reduced to 0.4 (in decimals) on both eyes. She had pronounced CME and slight vitritis (+1) in both eyes. The CME and vitritis resolved on treatment with systemic prednisone in high dose and visual acuity increased to 0.63 in both eyes. CME on the left eye, however, recurred 3 months after tapering prednisone (Fig. 1A), and visual acuity dropped down to 0.5. The patient was then treated with 1.5% dexamethasone–cyclodextrin ophthalmic solution four times daily for 1 month in the left eye. Visual acuity increased to 0.63 and the CME resolved (Fig. 1B). As dexamethasone– cyclodextrin eye drops are not available in Denmark, she then continued treatment with commercial dexamethasone eye drops, Maxidex â (Dexamethasone 0.1%; Alcon Inc, Fort Worth, TX, USA) 4 times daily in the left eye. After 1 month, the CME in the left eye had recurred (Fig. 1C), and she was subsequently treated with periocular triamcinolone acetonide and systemic prednisone in a low dose. A 84-year-old woman with bilateral vitritis and CME. Vitritis resolved after initating systemical treatment with mycophenolate mofetil. CME was persistent in both eyes (foveal thickness 357/ 332 lm). Visual acuity was 0.5 in both eyes. Right eye was treated with dexamethasone–cyclodextrin eye drops two drops four times daily tapered to one drop three times daily after 3 weeks. Left eye was treated with an intravitreal dexamethasone implant (Ozurdex; Allergan, Inc., Irvine, CA, USA). After 6 weeks of treatment, visual
e690
(A)
(B)
(C) Fig. 1. Optical Coherence Tomography images of the 54-year-old female with bilateral uveitic CME centred in the fovea (OCT; Cirrus, Carl Zeiss Meditec, Jena, Germany) before treatment with 1.5% dexamethasone–cyclodextrin nanoparticle eye drops (foveal thickness 404 lm) (A), after 1 month of treatment with the dexamethasone–cyclodextrin solution (foveal thickness 314 lm) (B) and subsequently after 1 month of treatment with Maxidex â (0.1% dexamethasone eye drops) (foveal thickness 390 lm) (C).
acuity was 0.8 in the right eye and 0.63 in the left eye, and the CME had resolved in both eyes (foveal thickness 315/317 lm). A 47-year-old woman with chronic, bilateral, posterior uveitis and CME. She was treated with Ozurdex in both eyes, but the CME recurred after 3 months. The Ozurdex implantation was repeated on the left eye. The right eye was treated with dexamethasone–cyclodextrin eye drops one drop six times daily for 1 week and then four times daily for 1 week. After 2 weeks of treatment, the CME in the right eye was increased further, and the eye received a new Ozurdex implant.
The present cases indicate that topical dexamethasone–cyclodextrin nanoparticle eye drops may be effective for the treatment of uveitic CME in some patients. In the first two cases, the CME was resolved after 1 month of treatment with this topical steroid formulation and recurred 1 month after treatment with conventional steroid eye drops. It therefore seems worth to explore the potential of dexamethasone–cyclodextrin nanoparticle eye drops for the treatment of uveitis with posterior manifestations as an alternative to periocular, intravitreal and systemic treatment with steroid. Periocular and intravitreal steroid carry a potential risk of ocular complications, and treatment with systemic steroid involves a considerable risk of serious systemic side-effects. Moreover, in children, the possibility of topical steroid treatment for uveitis with posterior manifestations would be of great benefit as treatment with periocular and intravitreal steroid in these patients requires a general anaesthetic prior to administration.
References Loftsson T & Stefansson E (2002): Cyclodextrins in eye drops formulations: enhanced topical delivery of corticosteroid to the eye. Acta Ophthalmol Scand 80: 144– 150. Loftsson T, Hreinsdottir D & Stefansson E (2007): Cyclodextrin microparticles for drug delivery to the posterior segment of the eye: aqueous dexamethasone eye drops. J Pharm Pharmacol 59: 629–635. Rothova A (2007): Inflammatory cystoid macular edema. Curr Opin Ophthalmol 18: 487–492. Tanito M, Hara K, Takai Y et al. (2011): Topical dexamethasone-cyclodextrin microparticle eye drops for diabetic macular edema. Invest Ophthalmol Vis Sci 52: 7944–7948.
Correspondence: Susanne Krag Department of Ophthalmology Aarhus University Hospital Nørrebrogade 44 8000 Aarhus Denmark Tel: +45 78 46 32 34 Fax: +45 78 46 32 26 Email: [email protected]
