Letters
vasoproliferative wound healing can affect bleb survival. Although reports have focused on the use of subconjunctival or subTenon injection of anti-VEGF agents in conjunction with trabeculectomy, the cumulative effect of repeated intravitreous injections on wound healing is likely similar.2,3 Furthermore, the wound-modulating effects of anti-VEGF agents may be dose dependent: a higher dosage or more frequent treatments may have a greater effect.4,5 Anti–vascular endothelial growth factor agents, especially if used in the perioperative period after trabeculectomy, result in blebs that are thinner and less vascular.1,2 The proposed benefit of anti-VEGF injections in trabeculectomy may result in complications associated with reduced wound healing with GDI surgery, as we have described. For nonvalved shunts to function, a pseudocapsule must form around the plate to allow adequate resistance to lower intraocular pressure without c ausing hypotony.6 It is possible that multiple anti-VEGF injections, especially in the perioperative period, may be related to thinner, more ischemic blebs that do not provide sufficient resistance to aqueous humor outflow. Hypotony occurs after GDI surgery in patients who do not receive anti-VEGF injections, and patients who receive these treatments can have successful outcomes. However, given the prevalence of glaucoma and the common use of anti-VEGF agents for AMD, these 2 cases suggest that this possible association needs further evaluation. In the meantime, those performing filtering surgery in patients who have had extensive anti-VEGF treatment should consider this possible complication. Ambika Hoguet, MD Richard K. Parrish II, MD Author Affiliations: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston (Hoguet); Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida (Parrish). Corresponding Author: Ambika Hoguet, MD, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114 ([email protected]). Published Online: December 4, 2014. doi:10.1001/jamaophthalmol.2014.5058. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Parrish reported serving on the scientific advisory boards of Alimera Sciences, Inc, AqueSys, Inc, Bausch & Lomb, Glaukos Corp, Merck and Co, Inc, and Aerie Pharmaceuticals, Inc; serving as a consultant to Alimera Sciences, Inc, Valeant Ophthalmics, Inc, and AbbVie Pharmaceuticals, Inc; receiving a grant from the National Eye Institute; receiving lecture fees from the Illinois Eye and Ear Infirmary, University of Illinois and University of California, San Francisco; and having stock options with InnFocus Inc, Aerie Pharmaceuticals, Inc, Innolene, LLC, AqueSys, Inc, and Glaukos Corp. No other disclosures were reported. Funding/Support: This work was supported by center core grant P0EY014801 from the National Institutes of Health, by an unrestricted grant from Research to Prevent Blindness, and by Strobis Glaucoma Foundation, Inc. Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. 1. Grewal DS, Jain R, Kumar H, Grewal SP. Evaluation of subconjunctival bevacizumab as an adjunct to trabeculectomy: a pilot study. Ophthalmology. 2008;115(12):2141-2145.e2. 2. Nomoto H, Shiraga F, Kuno N, et al. Pharmacokinetics of bevacizumab after topical, subconjunctival, and intravitreal administration in rabbits. Invest Ophthalmol Vis Sci. 2009;50(10):4807-4813. 350
3. Kahook MY. Bleb morphology and vascularity after trabeculectomy with intravitreal ranibizumab: a pilot study. Am J Ophthalmol. 2010;150(3):399-403.e1. 4. Ozgonul C, Mumcuoglu T, Gunal A. The effect of bevacizumab on wound healing modulation in an experimental trabeculectomy model. Curr Eye Res. 2014;39(5):451-459. 5. Guerriero E, Yu JY, Kahook MY, SundarRaj N, Schuman JS, Noecker RJ. Morphologic evaluation of bevacizumab (Avastin) treated corneal stromal fibroblasts [ARVO e-abstract 1642]. Invest Ophthalmol Vis Sci. 2006;47:1642. 6. Wilcox MJ, Minckler DS, Ogden TE. Pathophysiology of artificial aqueous drainage in primate eyes with Molteno implants. J Glaucoma. 1994;3(2):140-151.
In Vivo Cross-sectional Imaging of a Degrading Dexamethasone Intravitreal Implant That Became Attached to the Macula Dexamethasone intravitreal implant (Ozurdex) is a rodshaped biodegradable implant composed of polylactic coglycolic acid (PLGA) and 0.7 mg of dexamethasone. It has been shown to be effective for macular edema due to uveitis, retinal vein occlusion, or diabetic retinopathy.1,2 Two cases of macular attachment of the dexamethasone implant have been reported in a silicone oil (SO)–filled eye3,4 without longitudinal follow-up. We report the first case, to our knowledge, of a dexamethasone implant attaching to the macula in a vitrectomized eye without SO, with images revealing the implant’s in vivo absorption pattern. Report of a Case | A woman in her late 50s who had undergone cataract surgery and vitrectomy for vitreous hemorrhage from diabetic retinopathy 6 years earlier received a dexamethasone implant in her right eye for treatment of diabetic macular edema refractory to 5 intravitreous bevacizumab injections. The implantation was performed according to standard procedures.5 Two months after the implant injection, it was attached to the surface of the perifoveal macula. Spectral-domain optical coherence tomography (SD-OCT; Spectralis OCT, Heidelberg Engineering) showed that the implant was in contact with the inner surface of the retina and that the macular edema had decreased considerably. The size of the implant was measured using the caliper tool of the OCT imaging software. Three months after the injection, the implant remained attached to the perifoveal macula. Recurrence of mild macular edema was found on SD-OCT. Five months after the injection, fundus photography and SD-OCT showed that the implant had become a threadlike structure. Owing to aggravated macular edema, an intravitreous bevacizumab injection was administered. Six months after the implant injection, the implant was barely visible. Three-dimensional reconstruction of the SD-OCT images showed the absorption pattern of the implant: fragmentation along with size reduction (Figure 1). Figure 2 shows the changes in the size of the implant and the absorption rate of the implant: implant length in micrometers = 3323.6e−0.229(postinjection month); implantthicknessinmicrometers = 583.52e−0.335(postinjection month). Half-lives were 3.0 months for the implant length and 2.1 months for the implant thickness. Discussion | This case shows that a dexamethasone implant can become attached to the macula in a vitrectomized eye;
JAMA Ophthalmology March 2015 Volume 133, Number 3 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
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Letters
Figure 1. Images of the Dexamethasone Implant Attached to the Macula A
Preinjection
A1
200 µm
200 µm
A2
B
3 mo
A2 A1
2 mo 4 mo
3 mo
5 mo
5 mo
6 mo
6 mo
A, Fundus photographs (left) and optical coherence tomographic scans (right) show the dexamethasone intravitreal implant attached to the macula (arrowheads). B, Three-dimensional reconstructions of optical coherence
tomographic images show gradual volumetric decrease and fragmentation of the implant.
moreover, its serial absorption pattern can be visualized with SD-OCT. The macular attachment was tolerable and implant removal was not required. Serial in vivo crosssectional images of the implant showed that 2 months after the intravitreous injection, most of the drug and scaffold inside the implant had degraded, leaving a hollow, rodshaped, shell-like structure. Although the implant persisted for as long as 6 months, early dissipation of most of the drug inside the implant at 2 months indicates that drug efficacy may peak before 2 months after implantation. Chang-Lin et al6 reported that intravitreous drug concentration in monkeys peaked at 1 to 2 months and then showed rapid exponential decline from 2 to 6 months. Our findings are consistent with the findings by Chang-Lin and colleagues.
In 2 previous cases, a dexamethasone implant was trapped at the macula in an SO-filled eye.3,4 Afshar et al3 attributed the immobilization of the implant over 1 month to the nondynamic interaction between the SO and the potential fluid-filled space at the retinal surface. However, our case shows that in a vitrectomized eye not filled with SO, a dexamethasone implant can become attached to the macula within 6 months. In conclusion, the dexamethasone intravitreal implant can become attached to the macula in a vitrectomized eye not filled with SO. Furthermore, serial cross-sectional imaging of a displaced implant in the posterior pole provides insights into the degradation of the dexamethasone implant, potentially related to its typical duration of effect.
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(Reprinted) JAMA Ophthalmology March 2015 Volume 133, Number 3
Copyright 2015 American Medical Association. All rights reserved.
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351
Letters
Figure 2. Changes in the Size of the Dexamethasone Implant and Central Macular Thickness After Injection of the Implant 3500
y = 3323.6e-0.229x
Length of implant Macular thickness Thickness of implant Regression line for implant size
3000 2500
Size, µm
35% 2000
28%
1500
22% 17%
1000
14%
y = 583.52e-0.335x 500 0
Injection
1
62%
52%
2
3
35% 4
24% 5
17% 6
Follow-up, mo
Ji Ah Kim, MD Eun Ji Lee, MD Kyu Hyung Park, MD, PhD Se Joon Woo, MD, PhD
Clinical Heterogeneity in a Family With Mutations in USH2A
Author Affiliations: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea (Kim); Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea (Kim, Lee, Park, Woo). Corresponding Author: Se Joon Woo, MD, PhD, Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, No. 300 Gumi-dong, Bundang-gu, Seongnam, Gyeonggi-do 463-707, Korea ([email protected]). Published Online: December 18, 2014. doi:10.1001/jamaophthalmol.2014.5153. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Funding/Support: This study was supported in part by grant 2012R1A2A2A02012821 from the National Research Foundation of Korea. Role of the Funder/Sponsor: The National Research Foundation of Korea had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. 1. Haller JA, Bandello F, Belfort R Jr, et al; OZURDEX GENEVA Study Group. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology. 2010;117(6):1134-1146.e3. 2. London NJ, Chiang A, Haller JA. The dexamethasone drug delivery system: indications and evidence. Adv Ther. 2011;28(5):351-366. 3. Afshar AR, Loh AR, Pongsachareonnont P, Schwartz DM, Stewart JM. Dexamethasone intravitreal implant trapped at the macula in a silicone oil-filled eye. Ophthalmology. 2013;120(12):2748-2749.e1. 4. Banerjee PJ, Petrou P, Zvobgo TM, Charteris DG. Spontaneous relocation of a trapped retrolenticular slow-release dexamethasone implant (Ozurdex) in a silicone oil-filled eye of a pseudophakic patient. Eye (Lond). 2014;28(8):1036-1037. 5. Rishi P, Rishi E, Kuniyal L, Mathur G. Short-term results of intravitreal dexamethasone implant (OZURDEX(®)) in treatment of recalcitrant diabetic macular edema: a case series. Oman J Ophthalmol. 2012;5(2):79-82. 6. Chang-Lin JE, Burke JA, Peng Q, et al. Pharmacokinetics of a sustained-release dexamethasone intravitreal implant in vitrectomized and nonvitrectomized eyes. Invest Ophthalmol Vis Sci. 2011;52(7):4605-4609. 352
The absorption rate of the dexamethasone intravitreal implant decreased exponentially: implant length in micrometers = 3323.6e−0.229(postinjection month); implant thickness in micrometers = 583.52e−0.335(postinjection month). Half-lives were 3.0 months for the implant length and 2.1 months for the implant thickness. The percentages indicate the ratio between implant size and original implant size.
Patients with Usher syndrome typically have progressive visual impairment due to retinitis pigmentosa (RP) and varying levels of deafness with or without vestibular involvement. Usher syndrome type 2 is the most common of the 3 clinical subtypes that have been described; it is associated with RP, moderate to severe congenital hearing impairment, and normal vestibular function. Autosomal recessive mutations in USH2A are the most common cause of Usher syndrome type 2.1 Although a high degree of clinical heterogeneity has been described in USH2A-related disease, the ocular phenotype is usually concordant within families. Herein, we describe 2 siblings harboring the same USH2A mutations (c.[1036A>C];[13316C>T], p.[Asn346His];[Thr4439Ile]) with very different ocular and electrophysiological phenotypes. Report of Cases | Case 1. A 47-year-old man diagnosed as having Usher syndrome was referred for ophthalmic evaluation. He had been using hearing aids since age 3 years and did not report progressive hearing loss or balance problems. At age 30 years, an abnormal fundus appearance was noted during a routine eye examination. He had night vision problems from his late 20s and peripheral vision problems from his early 30s. On examination, his visual acuity was 0.3 logMAR (Snellen equivalent 20/40) OD and 0.6 logMAR (Snellen equivalent 20/80) OS. Visual fields to confrontation were constricted to less than 30° OU. Findings on fundus examination, autofluorescence imaging, optical coherence tomography, and electroretinograms were consistent with a diagnosis of RP (Figure 1A and Figure 2A). Sanger sequencing of all genes associated with Usher syndrome2 revealed 2 USH2A changes (p.Asn346His and p.Thr4439Ile, both reported multiple times to cause Usher syndrome3) and no other likely diseasecausing variants. Parental testing confirmed the biallelic nature of these changes. Case 2. A 43-year-old woman with no visual complaints, the sister of case 1, was examined. Hearing problems were noted at age
JAMA Ophthalmology March 2015 Volume 133, Number 3 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
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vasoproliferative wound healing can affect bleb survival. Although reports have focused on the use of subconjunctival or subTenon injection of anti-VEGF agents in conjunction with trabeculectomy, the cumulative effect of repeated intravitreous injections on wound healing is likely similar.2,3 Furthermore, the wound-modulating effects of anti-VEGF agents may be dose dependent: a higher dosage or more frequent treatments may have a greater effect.4,5 Anti–vascular endothelial growth factor agents, especially if used in the perioperative period after trabeculectomy, result in blebs that are thinner and less vascular.1,2 The proposed benefit of anti-VEGF injections in trabeculectomy may result in complications associated with reduced wound healing with GDI surgery, as we have described. For nonvalved shunts to function, a pseudocapsule must form around the plate to allow adequate resistance to lower intraocular pressure without c ausing hypotony.6 It is possible that multiple anti-VEGF injections, especially in the perioperative period, may be related to thinner, more ischemic blebs that do not provide sufficient resistance to aqueous humor outflow. Hypotony occurs after GDI surgery in patients who do not receive anti-VEGF injections, and patients who receive these treatments can have successful outcomes. However, given the prevalence of glaucoma and the common use of anti-VEGF agents for AMD, these 2 cases suggest that this possible association needs further evaluation. In the meantime, those performing filtering surgery in patients who have had extensive anti-VEGF treatment should consider this possible complication. Ambika Hoguet, MD Richard K. Parrish II, MD Author Affiliations: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston (Hoguet); Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida (Parrish). Corresponding Author: Ambika Hoguet, MD, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114 ([email protected]). Published Online: December 4, 2014. doi:10.1001/jamaophthalmol.2014.5058. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Parrish reported serving on the scientific advisory boards of Alimera Sciences, Inc, AqueSys, Inc, Bausch & Lomb, Glaukos Corp, Merck and Co, Inc, and Aerie Pharmaceuticals, Inc; serving as a consultant to Alimera Sciences, Inc, Valeant Ophthalmics, Inc, and AbbVie Pharmaceuticals, Inc; receiving a grant from the National Eye Institute; receiving lecture fees from the Illinois Eye and Ear Infirmary, University of Illinois and University of California, San Francisco; and having stock options with InnFocus Inc, Aerie Pharmaceuticals, Inc, Innolene, LLC, AqueSys, Inc, and Glaukos Corp. No other disclosures were reported. Funding/Support: This work was supported by center core grant P0EY014801 from the National Institutes of Health, by an unrestricted grant from Research to Prevent Blindness, and by Strobis Glaucoma Foundation, Inc. Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. 1. Grewal DS, Jain R, Kumar H, Grewal SP. Evaluation of subconjunctival bevacizumab as an adjunct to trabeculectomy: a pilot study. Ophthalmology. 2008;115(12):2141-2145.e2. 2. Nomoto H, Shiraga F, Kuno N, et al. Pharmacokinetics of bevacizumab after topical, subconjunctival, and intravitreal administration in rabbits. Invest Ophthalmol Vis Sci. 2009;50(10):4807-4813. 350
3. Kahook MY. Bleb morphology and vascularity after trabeculectomy with intravitreal ranibizumab: a pilot study. Am J Ophthalmol. 2010;150(3):399-403.e1. 4. Ozgonul C, Mumcuoglu T, Gunal A. The effect of bevacizumab on wound healing modulation in an experimental trabeculectomy model. Curr Eye Res. 2014;39(5):451-459. 5. Guerriero E, Yu JY, Kahook MY, SundarRaj N, Schuman JS, Noecker RJ. Morphologic evaluation of bevacizumab (Avastin) treated corneal stromal fibroblasts [ARVO e-abstract 1642]. Invest Ophthalmol Vis Sci. 2006;47:1642. 6. Wilcox MJ, Minckler DS, Ogden TE. Pathophysiology of artificial aqueous drainage in primate eyes with Molteno implants. J Glaucoma. 1994;3(2):140-151.
In Vivo Cross-sectional Imaging of a Degrading Dexamethasone Intravitreal Implant That Became Attached to the Macula Dexamethasone intravitreal implant (Ozurdex) is a rodshaped biodegradable implant composed of polylactic coglycolic acid (PLGA) and 0.7 mg of dexamethasone. It has been shown to be effective for macular edema due to uveitis, retinal vein occlusion, or diabetic retinopathy.1,2 Two cases of macular attachment of the dexamethasone implant have been reported in a silicone oil (SO)–filled eye3,4 without longitudinal follow-up. We report the first case, to our knowledge, of a dexamethasone implant attaching to the macula in a vitrectomized eye without SO, with images revealing the implant’s in vivo absorption pattern. Report of a Case | A woman in her late 50s who had undergone cataract surgery and vitrectomy for vitreous hemorrhage from diabetic retinopathy 6 years earlier received a dexamethasone implant in her right eye for treatment of diabetic macular edema refractory to 5 intravitreous bevacizumab injections. The implantation was performed according to standard procedures.5 Two months after the implant injection, it was attached to the surface of the perifoveal macula. Spectral-domain optical coherence tomography (SD-OCT; Spectralis OCT, Heidelberg Engineering) showed that the implant was in contact with the inner surface of the retina and that the macular edema had decreased considerably. The size of the implant was measured using the caliper tool of the OCT imaging software. Three months after the injection, the implant remained attached to the perifoveal macula. Recurrence of mild macular edema was found on SD-OCT. Five months after the injection, fundus photography and SD-OCT showed that the implant had become a threadlike structure. Owing to aggravated macular edema, an intravitreous bevacizumab injection was administered. Six months after the implant injection, the implant was barely visible. Three-dimensional reconstruction of the SD-OCT images showed the absorption pattern of the implant: fragmentation along with size reduction (Figure 1). Figure 2 shows the changes in the size of the implant and the absorption rate of the implant: implant length in micrometers = 3323.6e−0.229(postinjection month); implantthicknessinmicrometers = 583.52e−0.335(postinjection month). Half-lives were 3.0 months for the implant length and 2.1 months for the implant thickness. Discussion | This case shows that a dexamethasone implant can become attached to the macula in a vitrectomized eye;
JAMA Ophthalmology March 2015 Volume 133, Number 3 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
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Letters
Figure 1. Images of the Dexamethasone Implant Attached to the Macula A
Preinjection
A1
200 µm
200 µm
A2
B
3 mo
A2 A1
2 mo 4 mo
3 mo
5 mo
5 mo
6 mo
6 mo
A, Fundus photographs (left) and optical coherence tomographic scans (right) show the dexamethasone intravitreal implant attached to the macula (arrowheads). B, Three-dimensional reconstructions of optical coherence
tomographic images show gradual volumetric decrease and fragmentation of the implant.
moreover, its serial absorption pattern can be visualized with SD-OCT. The macular attachment was tolerable and implant removal was not required. Serial in vivo crosssectional images of the implant showed that 2 months after the intravitreous injection, most of the drug and scaffold inside the implant had degraded, leaving a hollow, rodshaped, shell-like structure. Although the implant persisted for as long as 6 months, early dissipation of most of the drug inside the implant at 2 months indicates that drug efficacy may peak before 2 months after implantation. Chang-Lin et al6 reported that intravitreous drug concentration in monkeys peaked at 1 to 2 months and then showed rapid exponential decline from 2 to 6 months. Our findings are consistent with the findings by Chang-Lin and colleagues.
In 2 previous cases, a dexamethasone implant was trapped at the macula in an SO-filled eye.3,4 Afshar et al3 attributed the immobilization of the implant over 1 month to the nondynamic interaction between the SO and the potential fluid-filled space at the retinal surface. However, our case shows that in a vitrectomized eye not filled with SO, a dexamethasone implant can become attached to the macula within 6 months. In conclusion, the dexamethasone intravitreal implant can become attached to the macula in a vitrectomized eye not filled with SO. Furthermore, serial cross-sectional imaging of a displaced implant in the posterior pole provides insights into the degradation of the dexamethasone implant, potentially related to its typical duration of effect.
jamaophthalmology.com
(Reprinted) JAMA Ophthalmology March 2015 Volume 133, Number 3
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a Karolinska Institutet University Library User on 06/02/2015
351
Letters
Figure 2. Changes in the Size of the Dexamethasone Implant and Central Macular Thickness After Injection of the Implant 3500
y = 3323.6e-0.229x
Length of implant Macular thickness Thickness of implant Regression line for implant size
3000 2500
Size, µm
35% 2000
28%
1500
22% 17%
1000
14%
y = 583.52e-0.335x 500 0
Injection
1
62%
52%
2
3
35% 4
24% 5
17% 6
Follow-up, mo
Ji Ah Kim, MD Eun Ji Lee, MD Kyu Hyung Park, MD, PhD Se Joon Woo, MD, PhD
Clinical Heterogeneity in a Family With Mutations in USH2A
Author Affiliations: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea (Kim); Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea (Kim, Lee, Park, Woo). Corresponding Author: Se Joon Woo, MD, PhD, Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, No. 300 Gumi-dong, Bundang-gu, Seongnam, Gyeonggi-do 463-707, Korea ([email protected]). Published Online: December 18, 2014. doi:10.1001/jamaophthalmol.2014.5153. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Funding/Support: This study was supported in part by grant 2012R1A2A2A02012821 from the National Research Foundation of Korea. Role of the Funder/Sponsor: The National Research Foundation of Korea had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. 1. Haller JA, Bandello F, Belfort R Jr, et al; OZURDEX GENEVA Study Group. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology. 2010;117(6):1134-1146.e3. 2. London NJ, Chiang A, Haller JA. The dexamethasone drug delivery system: indications and evidence. Adv Ther. 2011;28(5):351-366. 3. Afshar AR, Loh AR, Pongsachareonnont P, Schwartz DM, Stewart JM. Dexamethasone intravitreal implant trapped at the macula in a silicone oil-filled eye. Ophthalmology. 2013;120(12):2748-2749.e1. 4. Banerjee PJ, Petrou P, Zvobgo TM, Charteris DG. Spontaneous relocation of a trapped retrolenticular slow-release dexamethasone implant (Ozurdex) in a silicone oil-filled eye of a pseudophakic patient. Eye (Lond). 2014;28(8):1036-1037. 5. Rishi P, Rishi E, Kuniyal L, Mathur G. Short-term results of intravitreal dexamethasone implant (OZURDEX(®)) in treatment of recalcitrant diabetic macular edema: a case series. Oman J Ophthalmol. 2012;5(2):79-82. 6. Chang-Lin JE, Burke JA, Peng Q, et al. Pharmacokinetics of a sustained-release dexamethasone intravitreal implant in vitrectomized and nonvitrectomized eyes. Invest Ophthalmol Vis Sci. 2011;52(7):4605-4609. 352
The absorption rate of the dexamethasone intravitreal implant decreased exponentially: implant length in micrometers = 3323.6e−0.229(postinjection month); implant thickness in micrometers = 583.52e−0.335(postinjection month). Half-lives were 3.0 months for the implant length and 2.1 months for the implant thickness. The percentages indicate the ratio between implant size and original implant size.
Patients with Usher syndrome typically have progressive visual impairment due to retinitis pigmentosa (RP) and varying levels of deafness with or without vestibular involvement. Usher syndrome type 2 is the most common of the 3 clinical subtypes that have been described; it is associated with RP, moderate to severe congenital hearing impairment, and normal vestibular function. Autosomal recessive mutations in USH2A are the most common cause of Usher syndrome type 2.1 Although a high degree of clinical heterogeneity has been described in USH2A-related disease, the ocular phenotype is usually concordant within families. Herein, we describe 2 siblings harboring the same USH2A mutations (c.[1036A>C];[13316C>T], p.[Asn346His];[Thr4439Ile]) with very different ocular and electrophysiological phenotypes. Report of Cases | Case 1. A 47-year-old man diagnosed as having Usher syndrome was referred for ophthalmic evaluation. He had been using hearing aids since age 3 years and did not report progressive hearing loss or balance problems. At age 30 years, an abnormal fundus appearance was noted during a routine eye examination. He had night vision problems from his late 20s and peripheral vision problems from his early 30s. On examination, his visual acuity was 0.3 logMAR (Snellen equivalent 20/40) OD and 0.6 logMAR (Snellen equivalent 20/80) OS. Visual fields to confrontation were constricted to less than 30° OU. Findings on fundus examination, autofluorescence imaging, optical coherence tomography, and electroretinograms were consistent with a diagnosis of RP (Figure 1A and Figure 2A). Sanger sequencing of all genes associated with Usher syndrome2 revealed 2 USH2A changes (p.Asn346His and p.Thr4439Ile, both reported multiple times to cause Usher syndrome3) and no other likely diseasecausing variants. Parental testing confirmed the biallelic nature of these changes. Case 2. A 43-year-old woman with no visual complaints, the sister of case 1, was examined. Hearing problems were noted at age
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