- Email: [email protected]
Explanted Polyethylene Implants
ondary to -blockade, combined with brimonidine, a highly selective ␣-2-adrenergic agonist, resulted in vasoconstriction leading to decreased skin perfusion and subsequent necrosis. Furthermore, vascular tone in the digital circulation is mediated predominately via ␣-2-adrenoreceptors and the reactivity of these receptors is increased in both primary Raynaud’s phenomenon and cold temperatures.5 In summary, we report the development of peripheral skin necrosis in a patient with primary Raynaud’s phenomenon taking fixed-combination timolol maleate 0.5% and brimonidine tartrate 0.2%. Clinicians should be alert to this possible adverse reaction. NATHAN M. KERR, MBChB Auckland, New Zealand KEITH A. GROSS, MBBS Rotorua, New Zealand MICHAEL TOMBLESON, MBBCh Taupo, New Zealand
specifically in the American population aged 40 years and older.3 On the other hand, in a cohort study it has been shown that men with circulating 25(OH)D3 levels of at least 30 ng/ml had approximately half the risk of myocardial infarction, independent of other cardiovascular risk factors.4 To the best of our knowledge, the effect of vitamin D supplementation on the prevention and treatment of AMD has not been studied in a randomized trial. Among the several potential risk factors for the development of AMD, there is a growing interest in inflammation as an important potential risk factor for this disease. Vitamin D deficiency has been associated with a cytokine profile that favors greater inflammation (e.g., higher C-reactive protein and interleukin 6 levels, and lower interleukin 10 levels),5 which could predispose to both AMD and CHD. Therefore, if the association between vitamin D insufficiency and both AMD and CHD is proved to be causal, there would be broader implications for vitamin D supplementation for the prevention of these 2 common diseases. LUCA MASCITELLI, MD Udine, Italy
HELEN V. DANESH-MEYER, MD Auckland, New Zealand
FRANCESCA PEZZETTA, MD Tolmezzo, Italy
References 1. Gokal R, Dornan TL, Ledingham JG. Peripheral skin necrosis complicating beta-blockage. Br Med J 1979;1:721–2. 2. Coffman JD, Rasmussen HM. Effects of beta-adrenoreceptorblocking drugs in patients with Raynaud’s phenomenon. Circulation 1985;72:466 –70. 3. Everitt DE, Avorn J. Systemic effects of medications used to treat glaucoma. Ann Intern Med 1990;112:120 –5. 4. Meuche C, Heidrich H, Bleckmann H. [Raynaud syndrome following timolol-containing eyedrops]. Fortschr Ophthalmol 1990;87:45–7. 5. Furspan PB, Chatterjee S, Freedman RR. Increased tyrosine phosphorylation mediates the cooling-induced contraction and increased vascular reactivity of Raynaud’s disease. Arthritis Rheum 2004;50:1578 – 85.
Macular Degeneration, Heart Disease, and Vitamin D Dear Editor: Dr. Sun et al found that signs of early age-related macular degeneration (AMD) were associated with incident coronary heart disease (CHD) events.1 However, the mechanisms underlying this detrimental association are not fully understood. We suggest that vitamin D insufficiency might play a role in the development of both AMD and CHD. Vitamin D status is usually divided into 3 categories, based on serum 25-hydroxyvitamin D3 [25(OH)D3] levels: “deficient” (ⱕ15 ng/ml), “insufficient” (15.1–29.9 ng/ml), and “sufficient” (ⱖ30 ng/ml). Serum 25(OH)D3 levels have been decreasing significantly for more than a decade,2 resulting in a majority of the US population being categorized as vitamin D insufficient. A recent study found an inverse association between vitamin D status and the prevalence of early AMD; in particular, higher serum vitamin D levels were inversely associated with prevalent early AMD and with soft drusen,
194
MARK R. GOLDSTEIN, MD, FACP Bonita Springs, Florida References 1. Sun C, Klein R, Wong TY. Age-related macular degeneration and risk of coronary heart disease and stroke: The Cardiovascular Health Study. Ophthalmology 2009;116:1913–9. 2. Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med 2009;169:626 –32. 3. Parekh N, Chappell RJ, Millen AE, et al. Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Arch Ophthalmol 2007;125:661–9. 4. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med 2008;168:1174 – 80. 5. Mathieu C, Adorini L. The coming of age of 1,25-dihydroxyvitamin D(3) analogs as immunomodulatory agents. Trends Mol Med 2002;8:174 –9.
Explanted Polyethylene Implants Dear Editor: We would like to congratulate Dr. Chuo et al1 on their excellent histologic review of 18 explanted porous polyethylene orbital implants. We conducted a similar study on 6 porous orbital implants,2 and are well aware of the complexity and time consumption in the processing of these implants. In Dr. Chuo’s study, 89% of the implants contained less than 50% fibrovascular ingrowth. From the article, is unclear as to how the extent of fibrovascular ingrowth was graded, and it would be useful to know of these how many had fibrovascular ingrowth to the core, if at all. It would also be interesting to know how long these implants were in situ, as the time from surgery to implant removal varied from 4 to 168 months. In our study, all 5 porous polyethylene
implants were vascularized up to the core. The time from surgery to implant removal ranged from 11 to 64 months giving a longer period for complete vascularization of the implant. This information could help us understand the rate of vascularization of porous polyethylene implants. Another useful parameter would be to know if there was a greater propensity for the implants wrapped in sclera to resist vascularization. As in our series on histological examination, we found that there was scleral remodelling and thickening of the sclera with minimal fibrovascular growth through the sclera itself. In our study, we found that despite core vascularization, infection, and necrosis did set in. Thus, demonstrating that complete vascularization does not render the implant immune to infection. We do agree with the authors that the primary cause for exposure is more likely to be mechanical pressure, and that poor vascularization has a secondary role in contributing to poor wound healing. SOUPRAMANIEN SANDRAMOULI, MD, DNB, FRCS, FRCOPHTH KATYA TAMBE, MS, DNB, FRCS ED SHREEKUMARI PUSHPOTH, MS, MRCOPHTH Wolverhampton, UK HARDEEP MUDHAR, BSC, MBBCHIR, PHD, FRCPATH Sheffield, UK References 1. Chuo JY, Dolman PJ, Ng TL, et al. Clinical and histopathologic review of 18 explanted porous polyethylene orbital implants. Ophthalmology 2009;116:349 –54. 2. Tambe K, Pushpoth S, Mudhar H, Sandramouli S. A histopathologic study of orbital implant vascularization. Orbit 2009;28:50 –7.
Author reply Dear Editor: We would like to thank Dr. Sandramouli et al for their interest and comments. The extent of implant fibrovascular ingrowth in our study was graded by an ocular pathologist (Dr. Val White). The amount of viable and necrotic fibrovascular tissue present in each implant was estimated histologically as a percentage of the total implant volume on one section taken through the centre of the implant. Only one implant (with 90% fibrovascular ingrowth) had fibrovascular ingrowth to the core. Interestingly, we did not find a correlation between the time from surgery to explantation and the extent of implant vascularization; the implant with 90% fibrovascular ingrowth was removed 31 months after surgery, while the implant removed at 168 months after surgery was observed to have only 30% fibrovascular ingrowth. Nine of the 18 implants in our series were originally inserted by 1 of 2 oculoplastics surgeons (Dr. Peter Dolman or Dr. Frank Buffam) and were wrapped in donor sclera. Sclera was present histologically in all but 2 of the remaining implants, 1 of which was a post-evisceration specimen. As it is routine practice for Drs. Buffam and Dolman to wrap implants in donor sclera, it would therefore be difficult for us to comment on whether there was a greater propensity for sclera-wrapped implants to resist vascularization.
Dr Tambe et al found that complete fibrovascularization of the implants did not render them immune to infection. We agree with them in this regard. We would also argue that poor vascularization plays a pivotal role in facilitating infection as 17 of our 18 implants demonstrated no vascularization to the core. JEAN Y. CHUO, MD VAL A. WHITE, MD, FRCPC PETER J. DOLMAN, MD, FRCSC Vancouver, Canada
Propranolol for Orbital Hemangioma Dear Editor: We report our experience treating a large, refractory orbital capillary hemangioma with propranolol in a 6-week-old girl. Propranolol therapy for a periocular hemangioma was first reported by Léauté-Labrèze et al1 and also presented at the Fall Orbital Society meeting in New York. However, this therapy may still not be well known among the ophthalmic community. A 6-week-old girl was referred for management of a large left orbital and periorbital capillary hemangioma (Figs 1– 4; available at http://aaojournal.org). The neoplasm had been present since birth and getting progressively larger with resultant occlusive, anisometropic, and strabismic amblyopia of the left eye. She had received 1 intralesional steroid injection 2 weeks prior to presentation with no significant change. She also had 2 other cutaneous capillary hemangiomas on her scalp and abdomen (Fig 4; available at http://aaojournal.org). She was treated with systemic oral steroids (1 mg/kg/day). At 2 weeks follow-up, the tumor had not responded, or slightly progressed. She was then treated on outpatient basis with propranolol 2 mg/kg/day; simultaneously, oral steroids were tapered off over the next 2 weeks. She showed dramatic improvement, starting days after the initiation of the propranolol (Fig 2; available at http://aaojournal.org). The propranolol was continued over 2 months, concurrent with amblyopia therapy. At 6-month follow-up, 3 months after discontinuation of propranolol, there has been no regrowth of the orbital neoplasm (Figs 3– 4; available at http://aaojournal.org). Of note, her other cutaneous lesions resolved completely after being on propranolol for a few weeks (Fig 4; available at http://aaojournal. org). There was no systemic complication from using propranolol. The speed of resolution after initiating propranolol supports the role of propranolol in this case. Léauté-Labrèze et al reported the use of systemic propranolol for refractory capillary hemangiomas in 11 children.1 Systemic propranolol, at dose of 2 mg/kg/day, not only inhibited the growth of hemangioma, it resulted in involution. There was no rebound growth after discontinuation of therapy, unlike the case with systemic steroids. Their discovery of using -blocker for capillary hemangiomas was accidental. They reported that cutaneous and orbital capillary hemangiomas underwent color change and involution soon after initiation of systemic propranolol to treat high cardiac output. They subsequently used propranolol for other capillary hemangiomas, which had been refractory to therapy with systemic steroids. The mechanism of action of propranolol is not known, although various hypotheses have been proposed, including
195
specifically in the American population aged 40 years and older.3 On the other hand, in a cohort study it has been shown that men with circulating 25(OH)D3 levels of at least 30 ng/ml had approximately half the risk of myocardial infarction, independent of other cardiovascular risk factors.4 To the best of our knowledge, the effect of vitamin D supplementation on the prevention and treatment of AMD has not been studied in a randomized trial. Among the several potential risk factors for the development of AMD, there is a growing interest in inflammation as an important potential risk factor for this disease. Vitamin D deficiency has been associated with a cytokine profile that favors greater inflammation (e.g., higher C-reactive protein and interleukin 6 levels, and lower interleukin 10 levels),5 which could predispose to both AMD and CHD. Therefore, if the association between vitamin D insufficiency and both AMD and CHD is proved to be causal, there would be broader implications for vitamin D supplementation for the prevention of these 2 common diseases. LUCA MASCITELLI, MD Udine, Italy
HELEN V. DANESH-MEYER, MD Auckland, New Zealand
FRANCESCA PEZZETTA, MD Tolmezzo, Italy
References 1. Gokal R, Dornan TL, Ledingham JG. Peripheral skin necrosis complicating beta-blockage. Br Med J 1979;1:721–2. 2. Coffman JD, Rasmussen HM. Effects of beta-adrenoreceptorblocking drugs in patients with Raynaud’s phenomenon. Circulation 1985;72:466 –70. 3. Everitt DE, Avorn J. Systemic effects of medications used to treat glaucoma. Ann Intern Med 1990;112:120 –5. 4. Meuche C, Heidrich H, Bleckmann H. [Raynaud syndrome following timolol-containing eyedrops]. Fortschr Ophthalmol 1990;87:45–7. 5. Furspan PB, Chatterjee S, Freedman RR. Increased tyrosine phosphorylation mediates the cooling-induced contraction and increased vascular reactivity of Raynaud’s disease. Arthritis Rheum 2004;50:1578 – 85.
Macular Degeneration, Heart Disease, and Vitamin D Dear Editor: Dr. Sun et al found that signs of early age-related macular degeneration (AMD) were associated with incident coronary heart disease (CHD) events.1 However, the mechanisms underlying this detrimental association are not fully understood. We suggest that vitamin D insufficiency might play a role in the development of both AMD and CHD. Vitamin D status is usually divided into 3 categories, based on serum 25-hydroxyvitamin D3 [25(OH)D3] levels: “deficient” (ⱕ15 ng/ml), “insufficient” (15.1–29.9 ng/ml), and “sufficient” (ⱖ30 ng/ml). Serum 25(OH)D3 levels have been decreasing significantly for more than a decade,2 resulting in a majority of the US population being categorized as vitamin D insufficient. A recent study found an inverse association between vitamin D status and the prevalence of early AMD; in particular, higher serum vitamin D levels were inversely associated with prevalent early AMD and with soft drusen,
194
MARK R. GOLDSTEIN, MD, FACP Bonita Springs, Florida References 1. Sun C, Klein R, Wong TY. Age-related macular degeneration and risk of coronary heart disease and stroke: The Cardiovascular Health Study. Ophthalmology 2009;116:1913–9. 2. Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med 2009;169:626 –32. 3. Parekh N, Chappell RJ, Millen AE, et al. Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Arch Ophthalmol 2007;125:661–9. 4. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med 2008;168:1174 – 80. 5. Mathieu C, Adorini L. The coming of age of 1,25-dihydroxyvitamin D(3) analogs as immunomodulatory agents. Trends Mol Med 2002;8:174 –9.
Explanted Polyethylene Implants Dear Editor: We would like to congratulate Dr. Chuo et al1 on their excellent histologic review of 18 explanted porous polyethylene orbital implants. We conducted a similar study on 6 porous orbital implants,2 and are well aware of the complexity and time consumption in the processing of these implants. In Dr. Chuo’s study, 89% of the implants contained less than 50% fibrovascular ingrowth. From the article, is unclear as to how the extent of fibrovascular ingrowth was graded, and it would be useful to know of these how many had fibrovascular ingrowth to the core, if at all. It would also be interesting to know how long these implants were in situ, as the time from surgery to implant removal varied from 4 to 168 months. In our study, all 5 porous polyethylene
implants were vascularized up to the core. The time from surgery to implant removal ranged from 11 to 64 months giving a longer period for complete vascularization of the implant. This information could help us understand the rate of vascularization of porous polyethylene implants. Another useful parameter would be to know if there was a greater propensity for the implants wrapped in sclera to resist vascularization. As in our series on histological examination, we found that there was scleral remodelling and thickening of the sclera with minimal fibrovascular growth through the sclera itself. In our study, we found that despite core vascularization, infection, and necrosis did set in. Thus, demonstrating that complete vascularization does not render the implant immune to infection. We do agree with the authors that the primary cause for exposure is more likely to be mechanical pressure, and that poor vascularization has a secondary role in contributing to poor wound healing. SOUPRAMANIEN SANDRAMOULI, MD, DNB, FRCS, FRCOPHTH KATYA TAMBE, MS, DNB, FRCS ED SHREEKUMARI PUSHPOTH, MS, MRCOPHTH Wolverhampton, UK HARDEEP MUDHAR, BSC, MBBCHIR, PHD, FRCPATH Sheffield, UK References 1. Chuo JY, Dolman PJ, Ng TL, et al. Clinical and histopathologic review of 18 explanted porous polyethylene orbital implants. Ophthalmology 2009;116:349 –54. 2. Tambe K, Pushpoth S, Mudhar H, Sandramouli S. A histopathologic study of orbital implant vascularization. Orbit 2009;28:50 –7.
Author reply Dear Editor: We would like to thank Dr. Sandramouli et al for their interest and comments. The extent of implant fibrovascular ingrowth in our study was graded by an ocular pathologist (Dr. Val White). The amount of viable and necrotic fibrovascular tissue present in each implant was estimated histologically as a percentage of the total implant volume on one section taken through the centre of the implant. Only one implant (with 90% fibrovascular ingrowth) had fibrovascular ingrowth to the core. Interestingly, we did not find a correlation between the time from surgery to explantation and the extent of implant vascularization; the implant with 90% fibrovascular ingrowth was removed 31 months after surgery, while the implant removed at 168 months after surgery was observed to have only 30% fibrovascular ingrowth. Nine of the 18 implants in our series were originally inserted by 1 of 2 oculoplastics surgeons (Dr. Peter Dolman or Dr. Frank Buffam) and were wrapped in donor sclera. Sclera was present histologically in all but 2 of the remaining implants, 1 of which was a post-evisceration specimen. As it is routine practice for Drs. Buffam and Dolman to wrap implants in donor sclera, it would therefore be difficult for us to comment on whether there was a greater propensity for sclera-wrapped implants to resist vascularization.
Dr Tambe et al found that complete fibrovascularization of the implants did not render them immune to infection. We agree with them in this regard. We would also argue that poor vascularization plays a pivotal role in facilitating infection as 17 of our 18 implants demonstrated no vascularization to the core. JEAN Y. CHUO, MD VAL A. WHITE, MD, FRCPC PETER J. DOLMAN, MD, FRCSC Vancouver, Canada
Propranolol for Orbital Hemangioma Dear Editor: We report our experience treating a large, refractory orbital capillary hemangioma with propranolol in a 6-week-old girl. Propranolol therapy for a periocular hemangioma was first reported by Léauté-Labrèze et al1 and also presented at the Fall Orbital Society meeting in New York. However, this therapy may still not be well known among the ophthalmic community. A 6-week-old girl was referred for management of a large left orbital and periorbital capillary hemangioma (Figs 1– 4; available at http://aaojournal.org). The neoplasm had been present since birth and getting progressively larger with resultant occlusive, anisometropic, and strabismic amblyopia of the left eye. She had received 1 intralesional steroid injection 2 weeks prior to presentation with no significant change. She also had 2 other cutaneous capillary hemangiomas on her scalp and abdomen (Fig 4; available at http://aaojournal.org). She was treated with systemic oral steroids (1 mg/kg/day). At 2 weeks follow-up, the tumor had not responded, or slightly progressed. She was then treated on outpatient basis with propranolol 2 mg/kg/day; simultaneously, oral steroids were tapered off over the next 2 weeks. She showed dramatic improvement, starting days after the initiation of the propranolol (Fig 2; available at http://aaojournal.org). The propranolol was continued over 2 months, concurrent with amblyopia therapy. At 6-month follow-up, 3 months after discontinuation of propranolol, there has been no regrowth of the orbital neoplasm (Figs 3– 4; available at http://aaojournal.org). Of note, her other cutaneous lesions resolved completely after being on propranolol for a few weeks (Fig 4; available at http://aaojournal. org). There was no systemic complication from using propranolol. The speed of resolution after initiating propranolol supports the role of propranolol in this case. Léauté-Labrèze et al reported the use of systemic propranolol for refractory capillary hemangiomas in 11 children.1 Systemic propranolol, at dose of 2 mg/kg/day, not only inhibited the growth of hemangioma, it resulted in involution. There was no rebound growth after discontinuation of therapy, unlike the case with systemic steroids. Their discovery of using -blocker for capillary hemangiomas was accidental. They reported that cutaneous and orbital capillary hemangiomas underwent color change and involution soon after initiation of systemic propranolol to treat high cardiac output. They subsequently used propranolol for other capillary hemangiomas, which had been refractory to therapy with systemic steroids. The mechanism of action of propranolol is not known, although various hypotheses have been proposed, including
195