Letters
2. Wallow I, Johns K, Barry P, Chandra S, Bindley C. Chorioretinal and choriovitreal neovascularization after photocoagulation for proliferative diabetic retinopathy: a clinicopathologic correlation. Ophthalmology. 1985;92 (4):523-532.
linum toxin injection may alter the functioning of the meibomian glands that was not referenced by the authors. Ho and colleagues hypothesize that injection of botulinum toxin type A at the lateral canthus may diffuse to the pretarsal orbicularis and affect the emptying of the meibomian glands. As a diffusion radius of 2 to 4 cm would likely involve the pretarsal orbicularis, the authors hypothesize that “[p]aralysis of these muscles by botulinum toxin will decrease the driving force for meibomian oil excretion.”1 This is based on the pathology of the muscle of Riolan, which is a distinct subdivision of striated orbicularis muscle and is hypothesized to compress the meibomian gland ductules, aiding in expression of their contents.2 Recently, 2 groups independently reported the effect of paralysis of the orbicularis on meibomian gland morphology.3,4 Both groups found that patients with a unilateral facial nerve palsy had a significant difference in meibography results (using a numerical meiboscore3 or meibograde4) between the affected and unaffected sides. Shah et al3 examined 16 patients and demonstrated a significant difference between mean values for tear break-up time, eyelid abnormality, meiboscore of the upper and lower eyelids, and digital pressure. They found no difference for superficial punctate keratopathy or Schirmer test results. Call et al4 examined 20 patients and found a significant difference in the meibograde between the affected and unaffected sides of the lower eyelids in patients who had a facial nerve palsy longer than 3 months. These studies3,4 and the article by Ho et al1 have a number of clinical implications. Any condition that results in weakness of the orbicularis muscle will likely have a component of obstructive meibomian gland disease. We currently incorporate treatment of meibomian gland dysfunction in our patients with evidence of orbicularis weakness; this includes patients with previous eyelid surgery, facial nerve palsy, or myopathies that affect orbicularis strength (chronic progressive external ophthalmoplegia and myotonic dystrophy) and patients who receive periocular botulinum toxin injections for functional or cosmetic indications. At this time, one can only speculate as to whether involutional changes in the orbicularis muscle may contribute to the increased incidence of obstructive meibomian gland disease with age.
3. Freund KB, Zweifel SA, Engelbert M. Do we need a new classification for choroidal neovascularization in age-related macular degeneration? Retina. 2010;30(9):1333-1349.
Richard C. Allen, MD, PhD Ryan J. Wise, MD
dothelial growth factor and/or ischemic drive. Once anastomosed, the higher-pressure retinal circulation system then perfused the entire complex including the chorioretinal nodule and the extensive preretinal vascular network that formed part of the macular circulation. The vasoproliferative lesion was initially treated with photodynamic therapy and intravitreal anti–vascular endothelial growth factor therapy; however, it progressed and evolved into a preretinal vascular network with persistent exudation. While one might consider further treatments in an attempt to induce involution of the chorioretinal lesion, it was elected to observe the process in this case. Christine Y. Chen, PhD Michael Engelbert, MD K. Bailey Freund, MD Carol L. Shields, MD Gaetano Barile, MD Author Affiliations: Department of Surgery, Monash University, Melbourne, Australia (Chen); Centre for Eye Research Australia, University of Melbourne, Australia (Chen); Vitreous Retina Macula Consultants of New York, New York (Chen, Engelbert, Freund); LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, New York (Chen, Engelbert, Freund); Department of Ophthalmology, New York University School of Medicine, New York (Engelbert, Freund); Department of Ophthalmology, Columbia University, New York, New York (Freund); Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania (Shields); Department of Ophthalmology, Manhattan Eye, Ear, and Throat Hospital, New York, New York (Barile); now with Hofstra North Shore–LIJ School of Medicine, Hempstead, New York (Barile). Corresponding Author: Gaetano Barile, MD, Department of Ophthalmology, Manhattan Eye, Ear, and Throat Hospital, 210 E 64th St, Seventh Floor, New York, NY 10065 ([email protected]). Published Online: September 4, 2014. doi:10.1001/jamaophthalmol.2014.3297. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Freund reported having received personal fees as a consultant from Genentech, Regeneron, and Heidelberg Engineering. Dr Barile reported having received honoraria for participating on an advisory board for Genentech. No other disclosures were reported. 1. Lim JI. Iatrogenic choroidal neovascularization. Surv Ophthalmol. 1999;44(2): 95-111.
4. Shields CL, Kaliki S, Al-Dahmash S, et al. Retinal vasoproliferative tumors: comparative clinical features of primary vs secondary tumors in 334 cases. JAMA Ophthalmol. 2013;131(3):328-334.
Corresponding Author: Richard C. Allen, MD, PhD, Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Iowa City, IA 52242 ([email protected]).
COMMENT & RESPONSE
Orbicularis Oculi Weakness and Obstructive Meibomian Gland Disease To the Editor We read with special interest the article titled “Botulinum Toxin Type A Injection for Lateral Canthal Rhytids: Effect on Tear Film Stability and Tear Production” by Ho et al1 and offer additional support for the mechanism by which botu1490
Author Affiliations: Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, Iowa City (Allen); Department of Ophthalmology, University of Indiana School of Medicine, Indianapolis (Wise).
Published Online: September 11, 2014. doi:10.1001/jamaophthalmol.2014.2986. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Ho M-C, Hsu W-C, Hsieh Y-T. Botulinum toxin type A injection for lateral canthal rhytids: effect on tear film stability and tear production. JAMA Ophthalmol. 2014;132(3):332-337.
JAMA Ophthalmology December 2014 Volume 132, Number 12
Copyright 2014 American Medical Association. All rights reserved.
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Letters
2. Lipham WJ, Tawfik HA, Dutton JJ. A histologic analysis and three-dimensional reconstruction of the muscle of Riolan. Ophthal Plast Reconstr Surg. 2002;18(2):93-98. 3. Shah CT, Blount AL, Nguyen EV, Hassan AS. Cranial nerve seven palsy and its influence on meibomian gland function. Ophthal Plast Reconstr Surg. 2012;28 (3):166-168. 4. Call CB, Wise RJ, Hansen MR, Carter KD, Allen RC. In vivo examination of meibomian gland morphology in patients with facial nerve palsy using infrared meibography. Ophthal Plast Reconstr Surg. 2012;28(6):396-400.
Trypan Blue Vital Dye Staining vs TUNEL Technique to Detect Corneal Endothelium Toxic Effects To the Editor We read the article titled “Efficacy and Safety of Antifungal Additives in Optisol-GS Corneal Storage Medium” by Layer et al1 with interest. In their article, the authors investigated the efficacy and safety of voriconazole and amphotericin B in reducing Candida species contamination of Optisol-GS under normal storage conditions. Layer and colleagues used 0.4% trypan blue as a vital stain to evaluate corneal endothelium toxic effects. Trypan blue is primarily an indicator of membrane integrity and does not identify corneal endothelium undergoing apoptosis.2 Apoptosis is the principal form of cell death in the corneal endothelium under organ culture conditions.3 It was found that the mean percentage of cell death at the end of storage assessed by the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) technique is about 8-fold higher than when assessed by the trypan blue technique.2 We think the authors should also have shown apoptosis of corneal endothelium in their study.
Noelle L. Pruzan, MD Jeremy D. Keenan, MD, MPH Bennie H. Jeng, MD, MS Author Affiliations: Department of Ophthalmology, University of California, San Francisco (Pruzan, Keenan, Jeng); Francis I. Proctor Foundation, University of California, San Francisco (Keenan, Jeng); Department of Ophthalmology, San Francisco General Hospital, San Francisco, California (Jeng); Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore (Jeng). Corresponding Author: Bennie H. Jeng, MD, MS, Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, 419 W Redwood St, Ste 479, Baltimore, MD 21201 ([email protected]). Published Online: September 18, 2014. doi:10.1001/jamaophthalmol.2014.3614. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Sertan Goktas, MD Yasar Sakarya, MD Rabia Sakarya, MD
1. Park S, Fong AG, Cho H, et al. Protocol for vital dye staining of corneal endothelial cells. Cornea. 2012;31(12):1476-1479.
Author Affiliations: Department of Ophthalmology, Konya Training and Research Hospital, Konya, Turkey. Corresponding Author: Sertan Goktas, MD, Department of Ophthalmology, Konya Research and Training Hospital, 42090 Meram, Konya, Turkey ([email protected]). Published Online: September 18, 2014. doi:10.1001/jamaophthalmol.2014.3360. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Layer N, Cevallos V, Maxwell AJ, Hoover C, Keenan JD, Jeng BH. Efficacy and safety of antifungal additives in Optisol-GS corneal storage medium. JAMA Ophthalmol. 2014;132(7):832-837. 2. Gain P, Thuret G, Chiquet C, et al. Value of two mortality assessment techniques for organ cultured corneal endothelium: trypan blue versus TUNEL technique. Br J Ophthalmol. 2002;86(3):306-310. 3. Albon J, Tullo AB, Aktar S, Boulton ME. Apoptosis in the endothelium of human corneas for transplantation. Invest Ophthalmol Vis Sci. 2000;41(10): 2887-2893.
In Reply There is no gold standard or widely accepted staining protocol for assessing endothelial cell death in human corneas after storage. We followed the vital dye staining protocol proposed by Park et al,1 who validated the ability of trypan blue to detect endothelial damage by comparing corneas jamaophthalmology.com
exposed to hydrogen peroxide with those exposed to balanced salt solution and found that the optimal dye concentration was 0.4%. The only other study, to our knowledge, of an antifungal additive in Optisol-GS also used the trypan blue technique to evaluate corneal endothelial toxic effects.2 Gain et al 3 demonstrated that the TUNEL technique revealed a higher mean percentage of endothelial cell death compared with trypan blue staining, but they also found a significant correlation between the 2 methods. This implies that implementing the TUNEL technique would not change the relative values of our findings. However, we appreciate the potential of the TUNEL technique to reveal nonviable endothelial cells undetected by trypan blue staining, and we agree that it would be worthwhile to include this more sensitive method in further assessments of antifungal toxic effects.
2. Ritterband DC, Shah MK, Meskin SW, et al. Efficacy and safety of voriconazole as an additive in Optisol GS: a preservation medium for corneal donor tissue. Cornea. 2007;26(3):343-347. 3. Gain P, Thuret G, Chiquet C, et al. Value of two mortality assessment techniques for organ cultured corneal endothelium: trypan blue versus TUNEL technique. Br J Ophthalmol. 2002;86(3):306-310.
Comments on Infant Aphakia Treatment Study 4.5-Year Results To the Editor We read with interest the article on 4.5-year visual acuity outcomes for the Infant Aphakia Treatment Study (IATS).1 This is clearly a well-thought-out and meticulously devised study. The authors state that the study follows the intention-totreat principle. We feel that as not all the study participants met the outcome criteria, this study does not fit the definition of an intention-to-treat study, which should include all the participants. For example, only the participants who had at least 3 adherence assessments were included in the analysis. The authors conclude with this comment: “This study did not demonstrate any visual benefit from implanting an IOL [intraocular lens]….”1 With all due respect, this conclusion may be an overstatement. The study only looked at visual acuity JAMA Ophthalmology December 2014 Volume 132, Number 12
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/01/2015
1491
2. Wallow I, Johns K, Barry P, Chandra S, Bindley C. Chorioretinal and choriovitreal neovascularization after photocoagulation for proliferative diabetic retinopathy: a clinicopathologic correlation. Ophthalmology. 1985;92 (4):523-532.
linum toxin injection may alter the functioning of the meibomian glands that was not referenced by the authors. Ho and colleagues hypothesize that injection of botulinum toxin type A at the lateral canthus may diffuse to the pretarsal orbicularis and affect the emptying of the meibomian glands. As a diffusion radius of 2 to 4 cm would likely involve the pretarsal orbicularis, the authors hypothesize that “[p]aralysis of these muscles by botulinum toxin will decrease the driving force for meibomian oil excretion.”1 This is based on the pathology of the muscle of Riolan, which is a distinct subdivision of striated orbicularis muscle and is hypothesized to compress the meibomian gland ductules, aiding in expression of their contents.2 Recently, 2 groups independently reported the effect of paralysis of the orbicularis on meibomian gland morphology.3,4 Both groups found that patients with a unilateral facial nerve palsy had a significant difference in meibography results (using a numerical meiboscore3 or meibograde4) between the affected and unaffected sides. Shah et al3 examined 16 patients and demonstrated a significant difference between mean values for tear break-up time, eyelid abnormality, meiboscore of the upper and lower eyelids, and digital pressure. They found no difference for superficial punctate keratopathy or Schirmer test results. Call et al4 examined 20 patients and found a significant difference in the meibograde between the affected and unaffected sides of the lower eyelids in patients who had a facial nerve palsy longer than 3 months. These studies3,4 and the article by Ho et al1 have a number of clinical implications. Any condition that results in weakness of the orbicularis muscle will likely have a component of obstructive meibomian gland disease. We currently incorporate treatment of meibomian gland dysfunction in our patients with evidence of orbicularis weakness; this includes patients with previous eyelid surgery, facial nerve palsy, or myopathies that affect orbicularis strength (chronic progressive external ophthalmoplegia and myotonic dystrophy) and patients who receive periocular botulinum toxin injections for functional or cosmetic indications. At this time, one can only speculate as to whether involutional changes in the orbicularis muscle may contribute to the increased incidence of obstructive meibomian gland disease with age.
3. Freund KB, Zweifel SA, Engelbert M. Do we need a new classification for choroidal neovascularization in age-related macular degeneration? Retina. 2010;30(9):1333-1349.
Richard C. Allen, MD, PhD Ryan J. Wise, MD
dothelial growth factor and/or ischemic drive. Once anastomosed, the higher-pressure retinal circulation system then perfused the entire complex including the chorioretinal nodule and the extensive preretinal vascular network that formed part of the macular circulation. The vasoproliferative lesion was initially treated with photodynamic therapy and intravitreal anti–vascular endothelial growth factor therapy; however, it progressed and evolved into a preretinal vascular network with persistent exudation. While one might consider further treatments in an attempt to induce involution of the chorioretinal lesion, it was elected to observe the process in this case. Christine Y. Chen, PhD Michael Engelbert, MD K. Bailey Freund, MD Carol L. Shields, MD Gaetano Barile, MD Author Affiliations: Department of Surgery, Monash University, Melbourne, Australia (Chen); Centre for Eye Research Australia, University of Melbourne, Australia (Chen); Vitreous Retina Macula Consultants of New York, New York (Chen, Engelbert, Freund); LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, New York (Chen, Engelbert, Freund); Department of Ophthalmology, New York University School of Medicine, New York (Engelbert, Freund); Department of Ophthalmology, Columbia University, New York, New York (Freund); Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania (Shields); Department of Ophthalmology, Manhattan Eye, Ear, and Throat Hospital, New York, New York (Barile); now with Hofstra North Shore–LIJ School of Medicine, Hempstead, New York (Barile). Corresponding Author: Gaetano Barile, MD, Department of Ophthalmology, Manhattan Eye, Ear, and Throat Hospital, 210 E 64th St, Seventh Floor, New York, NY 10065 ([email protected]). Published Online: September 4, 2014. doi:10.1001/jamaophthalmol.2014.3297. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Freund reported having received personal fees as a consultant from Genentech, Regeneron, and Heidelberg Engineering. Dr Barile reported having received honoraria for participating on an advisory board for Genentech. No other disclosures were reported. 1. Lim JI. Iatrogenic choroidal neovascularization. Surv Ophthalmol. 1999;44(2): 95-111.
4. Shields CL, Kaliki S, Al-Dahmash S, et al. Retinal vasoproliferative tumors: comparative clinical features of primary vs secondary tumors in 334 cases. JAMA Ophthalmol. 2013;131(3):328-334.
Corresponding Author: Richard C. Allen, MD, PhD, Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Iowa City, IA 52242 ([email protected]).
COMMENT & RESPONSE
Orbicularis Oculi Weakness and Obstructive Meibomian Gland Disease To the Editor We read with special interest the article titled “Botulinum Toxin Type A Injection for Lateral Canthal Rhytids: Effect on Tear Film Stability and Tear Production” by Ho et al1 and offer additional support for the mechanism by which botu1490
Author Affiliations: Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, Iowa City (Allen); Department of Ophthalmology, University of Indiana School of Medicine, Indianapolis (Wise).
Published Online: September 11, 2014. doi:10.1001/jamaophthalmol.2014.2986. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Ho M-C, Hsu W-C, Hsieh Y-T. Botulinum toxin type A injection for lateral canthal rhytids: effect on tear film stability and tear production. JAMA Ophthalmol. 2014;132(3):332-337.
JAMA Ophthalmology December 2014 Volume 132, Number 12
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/01/2015
jamaophthalmology.com
Letters
2. Lipham WJ, Tawfik HA, Dutton JJ. A histologic analysis and three-dimensional reconstruction of the muscle of Riolan. Ophthal Plast Reconstr Surg. 2002;18(2):93-98. 3. Shah CT, Blount AL, Nguyen EV, Hassan AS. Cranial nerve seven palsy and its influence on meibomian gland function. Ophthal Plast Reconstr Surg. 2012;28 (3):166-168. 4. Call CB, Wise RJ, Hansen MR, Carter KD, Allen RC. In vivo examination of meibomian gland morphology in patients with facial nerve palsy using infrared meibography. Ophthal Plast Reconstr Surg. 2012;28(6):396-400.
Trypan Blue Vital Dye Staining vs TUNEL Technique to Detect Corneal Endothelium Toxic Effects To the Editor We read the article titled “Efficacy and Safety of Antifungal Additives in Optisol-GS Corneal Storage Medium” by Layer et al1 with interest. In their article, the authors investigated the efficacy and safety of voriconazole and amphotericin B in reducing Candida species contamination of Optisol-GS under normal storage conditions. Layer and colleagues used 0.4% trypan blue as a vital stain to evaluate corneal endothelium toxic effects. Trypan blue is primarily an indicator of membrane integrity and does not identify corneal endothelium undergoing apoptosis.2 Apoptosis is the principal form of cell death in the corneal endothelium under organ culture conditions.3 It was found that the mean percentage of cell death at the end of storage assessed by the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) technique is about 8-fold higher than when assessed by the trypan blue technique.2 We think the authors should also have shown apoptosis of corneal endothelium in their study.
Noelle L. Pruzan, MD Jeremy D. Keenan, MD, MPH Bennie H. Jeng, MD, MS Author Affiliations: Department of Ophthalmology, University of California, San Francisco (Pruzan, Keenan, Jeng); Francis I. Proctor Foundation, University of California, San Francisco (Keenan, Jeng); Department of Ophthalmology, San Francisco General Hospital, San Francisco, California (Jeng); Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore (Jeng). Corresponding Author: Bennie H. Jeng, MD, MS, Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, 419 W Redwood St, Ste 479, Baltimore, MD 21201 ([email protected]). Published Online: September 18, 2014. doi:10.1001/jamaophthalmol.2014.3614. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Sertan Goktas, MD Yasar Sakarya, MD Rabia Sakarya, MD
1. Park S, Fong AG, Cho H, et al. Protocol for vital dye staining of corneal endothelial cells. Cornea. 2012;31(12):1476-1479.
Author Affiliations: Department of Ophthalmology, Konya Training and Research Hospital, Konya, Turkey. Corresponding Author: Sertan Goktas, MD, Department of Ophthalmology, Konya Research and Training Hospital, 42090 Meram, Konya, Turkey ([email protected]). Published Online: September 18, 2014. doi:10.1001/jamaophthalmol.2014.3360. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Layer N, Cevallos V, Maxwell AJ, Hoover C, Keenan JD, Jeng BH. Efficacy and safety of antifungal additives in Optisol-GS corneal storage medium. JAMA Ophthalmol. 2014;132(7):832-837. 2. Gain P, Thuret G, Chiquet C, et al. Value of two mortality assessment techniques for organ cultured corneal endothelium: trypan blue versus TUNEL technique. Br J Ophthalmol. 2002;86(3):306-310. 3. Albon J, Tullo AB, Aktar S, Boulton ME. Apoptosis in the endothelium of human corneas for transplantation. Invest Ophthalmol Vis Sci. 2000;41(10): 2887-2893.
In Reply There is no gold standard or widely accepted staining protocol for assessing endothelial cell death in human corneas after storage. We followed the vital dye staining protocol proposed by Park et al,1 who validated the ability of trypan blue to detect endothelial damage by comparing corneas jamaophthalmology.com
exposed to hydrogen peroxide with those exposed to balanced salt solution and found that the optimal dye concentration was 0.4%. The only other study, to our knowledge, of an antifungal additive in Optisol-GS also used the trypan blue technique to evaluate corneal endothelial toxic effects.2 Gain et al 3 demonstrated that the TUNEL technique revealed a higher mean percentage of endothelial cell death compared with trypan blue staining, but they also found a significant correlation between the 2 methods. This implies that implementing the TUNEL technique would not change the relative values of our findings. However, we appreciate the potential of the TUNEL technique to reveal nonviable endothelial cells undetected by trypan blue staining, and we agree that it would be worthwhile to include this more sensitive method in further assessments of antifungal toxic effects.
2. Ritterband DC, Shah MK, Meskin SW, et al. Efficacy and safety of voriconazole as an additive in Optisol GS: a preservation medium for corneal donor tissue. Cornea. 2007;26(3):343-347. 3. Gain P, Thuret G, Chiquet C, et al. Value of two mortality assessment techniques for organ cultured corneal endothelium: trypan blue versus TUNEL technique. Br J Ophthalmol. 2002;86(3):306-310.
Comments on Infant Aphakia Treatment Study 4.5-Year Results To the Editor We read with interest the article on 4.5-year visual acuity outcomes for the Infant Aphakia Treatment Study (IATS).1 This is clearly a well-thought-out and meticulously devised study. The authors state that the study follows the intention-totreat principle. We feel that as not all the study participants met the outcome criteria, this study does not fit the definition of an intention-to-treat study, which should include all the participants. For example, only the participants who had at least 3 adherence assessments were included in the analysis. The authors conclude with this comment: “This study did not demonstrate any visual benefit from implanting an IOL [intraocular lens]….”1 With all due respect, this conclusion may be an overstatement. The study only looked at visual acuity JAMA Ophthalmology December 2014 Volume 132, Number 12
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/01/2015
1491
