Zinc and Macular
Degeneration
To the Editor.\p=m-\Duringthe past year, ophthalmologists have been subjected to an extensive publicity campaign regarding the role of micronutrients, especially zinc supplementation in the treatment of macular degeneration. The article by Newsome et al1 in the February 1988 issue of the ARCHIVES is often quoted to substantiate this advertising. In the study done by the authors, 200 mg of zinc was given daily to patients with macular degeneration. This is a toxic amount of zinc that can produce serious complications. The recommended daily allowance is 15 mg. When more than 150 mg of zinc is taken, it can produce serious copper deficiency, sideroblastic anemia, and bone marrow depression.2 Such patients must often undergo costly and unpleasant tests, such as bone marrow biopsy, to determine the cause of the anemia. It is important for clinicians to be aware of this possible complication when prescribing large amounts of zinc to patients. The beneficial effect of a toxic amount of zinc on macular degeneration could be the result of the hypocupremia, hyperceruloplasminemia, and neutropenia produced by this amount of zinc. There is extensive evidence suggesting that the white blood cells play an important role in subretinal neovascularization, and in neovascularization in general. Copper is also important in angiogenesis; without it, several angiogenic agents become inactive. Further studies are needed to determine the role of zinc-induced copper defi¬ ciency on subretinal neovascularization. Further studies are also needed to determine if patients with age-related macu¬ lar degeneration are deficient in zinc. Studies have shown a significant increase rather than a decrease in zinc in such
patients.3
Clement L. Trempe, MD Boston, Mass 1. Newsome DA, Swartz M, Leone ND, Elston RC, Miller E. Oral zinc in macular degeneration. Arch Ophthalmol. 1988;106:192-198. 2. Brown ER, Griest A, Tricot G, Hoffman R. Excessive zinc ingestion: a reversible cause of sideroblastic anemia and bone marrow depression. JAMA. 1990;264:1441-1443. 3. Sues FE, Klaus U. Aspects epidemiologique de la degenerescence maculaire liee a l'age. Ophthalmologie. 1992;6:3-7.
In Reply.\p=m-\DrTrempe seems unaware of a number of other clinical studies that have been published, at least in the popular press.1 He exaggerates by calling 200 mg of zinc acetate "toxic." Not only did we not see evidence of toxic effects in our study, but also some physicians have given similar amounts to patients for many years without evidence of "toxicity."2 Zinc sulfate is an emetic, and it is unlikely that one could ingest a truly toxic dose repeatedly. To have megaloblastic anemia, large amounts of zinc have to be ingested and retained by a patient.3 Although some of the subjects in the serum ceruloplasmin study4 later participated in our clinical trial, no subject was known to be taking "large amounts of zinc" when the serum samples that we studied were obtained. David A. Newsome, MD New Orleans, La
1. Bruce RA Jr, Faulkner GD, Pomerance GN, et al. Nutritional compliance and macular degeneration: is it an untreatable disease? Ocular Surg News.
1991;9(suppl):1-14.
2. Yuzbasizan-Gurkan V, Brewer GJ. The therapeutic use of zinc in macular degeneration. Arch Ophthalmol. 1989;107:1723. 3. Broun ER, Greist A, Tricot G, Hoffman R. Excessive zinc ingestion: a reversible cause of sideroblastic anemia and bone marrow depression. JAMA.
1990;264:1441-1443. 4. Newsome DA, Swartz M, Leone NC, Hewitt AT, Wolford F, Miller ED.
Macular degeneration and elevated Vis Sci. 1986;27:1675-1680.
The Collaborative Corneal
serum
ceruloplasmin. Invest Ophthalmol
Transplantation Studies
To the Editor.\p=m-\Theresults of the Collaborative Corneal Studies (CCTS)1 provide exciting and important information that may run counter to the expectations of many. It is important, as the authors point out, to note that the use of topical corticosteroids in the study was significantly more intensive than use both by many corneal surgeons and in prior similar studies. An important conclusion from their study may well be that patients receiving high-risk corneal transplants warrant more intensive topical corticosteroid use. This intensive use of topical corticosteroids may have overwhelmed any potential beneficial effect of HLA-A, -B, and -DR matching. While all of this was well stated in the article, the casual reader reviewing only the abstract may have missed this important point. Joel Sugar, MD Chicago, Ill 1. The Collaborative Corneal Transplantation Studies Research Group. The Collaborative Corneal Transplantation Studies (CCTS): effectiveness of histocompatibility matching in high-risk corneal transplantation. Arch Ophthalmol.
Transplantation
1992;110:1392-1403.
In
Reply.\p=m-\DrSugar appropriately emphasizes a point that
we made in the "Comment" section of our article. We also men-
tioned two additional factors that may have contributed to the relatively high success rate for penetrating keratoplasty in the CCTS: a vigorous educational program to assure medication compliance, and frequent, regular follow-up examinations by the transplanting surgeon. The CCTS patients were outstanding in that only 4% of all visits were missed and only 1% of patients were considered unavailable for follow-up. When we formulated the protocol for the CCTS, we were aware that high doses of postoperative steroids could mask any effect of HLA matching on corneal transplant survival. However, our goal was not to design a study that would maximize the likelihood of observing a beneficial HLA matching. Instead, we sought to determine whether HLA matching would improve graft survival when used in addition to the postoperative immunosuppressive regimen routinely employed by corneal surgeons. We reasoned that a more intensive postoperative steroid regimen would be more practical and cost-effective than HLA matching in improving corneal graft survival (if there were no increase in complica¬ tions with the medication). During protocol development, the CCTS surgeons reached a consensus on the postoperative steroid regimen to be used. We considered risks, benefits, ethics, science, and common
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Degeneration
To the Editor.\p=m-\Duringthe past year, ophthalmologists have been subjected to an extensive publicity campaign regarding the role of micronutrients, especially zinc supplementation in the treatment of macular degeneration. The article by Newsome et al1 in the February 1988 issue of the ARCHIVES is often quoted to substantiate this advertising. In the study done by the authors, 200 mg of zinc was given daily to patients with macular degeneration. This is a toxic amount of zinc that can produce serious complications. The recommended daily allowance is 15 mg. When more than 150 mg of zinc is taken, it can produce serious copper deficiency, sideroblastic anemia, and bone marrow depression.2 Such patients must often undergo costly and unpleasant tests, such as bone marrow biopsy, to determine the cause of the anemia. It is important for clinicians to be aware of this possible complication when prescribing large amounts of zinc to patients. The beneficial effect of a toxic amount of zinc on macular degeneration could be the result of the hypocupremia, hyperceruloplasminemia, and neutropenia produced by this amount of zinc. There is extensive evidence suggesting that the white blood cells play an important role in subretinal neovascularization, and in neovascularization in general. Copper is also important in angiogenesis; without it, several angiogenic agents become inactive. Further studies are needed to determine the role of zinc-induced copper defi¬ ciency on subretinal neovascularization. Further studies are also needed to determine if patients with age-related macu¬ lar degeneration are deficient in zinc. Studies have shown a significant increase rather than a decrease in zinc in such
patients.3
Clement L. Trempe, MD Boston, Mass 1. Newsome DA, Swartz M, Leone ND, Elston RC, Miller E. Oral zinc in macular degeneration. Arch Ophthalmol. 1988;106:192-198. 2. Brown ER, Griest A, Tricot G, Hoffman R. Excessive zinc ingestion: a reversible cause of sideroblastic anemia and bone marrow depression. JAMA. 1990;264:1441-1443. 3. Sues FE, Klaus U. Aspects epidemiologique de la degenerescence maculaire liee a l'age. Ophthalmologie. 1992;6:3-7.
In Reply.\p=m-\DrTrempe seems unaware of a number of other clinical studies that have been published, at least in the popular press.1 He exaggerates by calling 200 mg of zinc acetate "toxic." Not only did we not see evidence of toxic effects in our study, but also some physicians have given similar amounts to patients for many years without evidence of "toxicity."2 Zinc sulfate is an emetic, and it is unlikely that one could ingest a truly toxic dose repeatedly. To have megaloblastic anemia, large amounts of zinc have to be ingested and retained by a patient.3 Although some of the subjects in the serum ceruloplasmin study4 later participated in our clinical trial, no subject was known to be taking "large amounts of zinc" when the serum samples that we studied were obtained. David A. Newsome, MD New Orleans, La
1. Bruce RA Jr, Faulkner GD, Pomerance GN, et al. Nutritional compliance and macular degeneration: is it an untreatable disease? Ocular Surg News.
1991;9(suppl):1-14.
2. Yuzbasizan-Gurkan V, Brewer GJ. The therapeutic use of zinc in macular degeneration. Arch Ophthalmol. 1989;107:1723. 3. Broun ER, Greist A, Tricot G, Hoffman R. Excessive zinc ingestion: a reversible cause of sideroblastic anemia and bone marrow depression. JAMA.
1990;264:1441-1443. 4. Newsome DA, Swartz M, Leone NC, Hewitt AT, Wolford F, Miller ED.
Macular degeneration and elevated Vis Sci. 1986;27:1675-1680.
The Collaborative Corneal
serum
ceruloplasmin. Invest Ophthalmol
Transplantation Studies
To the Editor.\p=m-\Theresults of the Collaborative Corneal Studies (CCTS)1 provide exciting and important information that may run counter to the expectations of many. It is important, as the authors point out, to note that the use of topical corticosteroids in the study was significantly more intensive than use both by many corneal surgeons and in prior similar studies. An important conclusion from their study may well be that patients receiving high-risk corneal transplants warrant more intensive topical corticosteroid use. This intensive use of topical corticosteroids may have overwhelmed any potential beneficial effect of HLA-A, -B, and -DR matching. While all of this was well stated in the article, the casual reader reviewing only the abstract may have missed this important point. Joel Sugar, MD Chicago, Ill 1. The Collaborative Corneal Transplantation Studies Research Group. The Collaborative Corneal Transplantation Studies (CCTS): effectiveness of histocompatibility matching in high-risk corneal transplantation. Arch Ophthalmol.
Transplantation
1992;110:1392-1403.
In
Reply.\p=m-\DrSugar appropriately emphasizes a point that
we made in the "Comment" section of our article. We also men-
tioned two additional factors that may have contributed to the relatively high success rate for penetrating keratoplasty in the CCTS: a vigorous educational program to assure medication compliance, and frequent, regular follow-up examinations by the transplanting surgeon. The CCTS patients were outstanding in that only 4% of all visits were missed and only 1% of patients were considered unavailable for follow-up. When we formulated the protocol for the CCTS, we were aware that high doses of postoperative steroids could mask any effect of HLA matching on corneal transplant survival. However, our goal was not to design a study that would maximize the likelihood of observing a beneficial HLA matching. Instead, we sought to determine whether HLA matching would improve graft survival when used in addition to the postoperative immunosuppressive regimen routinely employed by corneal surgeons. We reasoned that a more intensive postoperative steroid regimen would be more practical and cost-effective than HLA matching in improving corneal graft survival (if there were no increase in complica¬ tions with the medication). During protocol development, the CCTS surgeons reached a consensus on the postoperative steroid regimen to be used. We considered risks, benefits, ethics, science, and common
Downloaded From: http://archopht.jamanetwork.com/ by a University of Victoria User on 06/05/2015
