Race, Macular Degeneration, and the Macular
Photocoagulation Study
Macular Photocoagulation Study (MPS) is The multicenter, collaborative, clinical trial that vides for the of choroi-
a
important guidelines
treatment
pro-
age-related macular degeneration (AMD), presumed ocular histoplasmosis syndrome (POHS), and idiopathic neovascularization. In a previous editorial, Jampol1 discussed the role of hypertension among patients in the MPS, showing that under some circumstances, patients with hypertension had a less beneficial response to laser photocoagulation. dal neovascularization from
Another aspect of the MPS that has received almost no attention to date is the racial characteristics of patients enrolled in the trial. See also p 1701.
The MPS includes three clinical trials for AMD:
argon-laser photocoagulation for extrafoveal membranes, krypton-laser photocoagulation for juxtafoveal membranes, and argon or krypton laser photocoagulation for subfoveal membranes. As of July 1,1991, a total of 1319 patients had been enrolled in these trials (Maureen Maguire, PhD, written communication). Of these patients, 1314 were white, one was black, and four
were
listed
as
"other." This leads to
an
astonish¬
ing statistic: only 0.08% of the patients were black. Al¬ though arguments can be made that blacks, due to eco¬ nomic, cultural, geographic, or other reasons, might be less likely to enroll in a randomized trial, other oph¬ thalmic clinical trials performed at similar academic institutions across the country have had a much higher percentage of black participants. For example, the Di¬ abetic Retinopathy Study had 5.9% black patients, the Early Treatment Diabetic Study had 13.6%, the Dia¬ betic Retinopathy Vitrectomy Study had 12.1%, and the Collaborative Corneal Transplantation Studies had 15.5%. We have not quoted percentages from analogous studies of ocular melanoma or glaucoma, because
blacks are believed to have a decreased incidence of choroidal melanoma and an increased incidence of open angle glaucoma. The prevalence of a racial group within the enrollees of a randomized study certainly does not represent their prevalence in the total population at risk, but the MPS data indicate that choroidal neovas¬ cularization from AMD is extremely rare in blacks. Similar clinical trials have also been performed in the
MPS on patients with POHS: argon laser for ex¬ trafoveal membranes, and krypton laser for jux¬ tafoveal membranes. Smaller trials have been per¬ formed on patients with idiopathic neovascularization. As of July 1, 1991, a total of 667 patients had been en¬ rolled in these various trials. Sixteen patients (2.4%) were black. By combining AMD, POHS, and idiopathic neovasculariaztion, a total of 1986 patients had been enrolled, and just 17 (0.9%) were black. Many clinicians believe that disciform macular de¬ generation with choroidal neovascularization is much rarer in blacks, with a variety of causes, including AMD, ocular histoplasmosis, and perhaps other dis¬ eases, such as angioid streaks. Until recently there were relatively few studies in this area. In the Bal¬ timore Eye Survey,2 among 5308 persons 40 years of age and older participating in this population-based sample, blacks had more than twice the age-adjusted rate of legal blindness as did whites (1.75% as op¬ posed to 0.76%). Among whites, AMD was the lead¬ ing cause of bilateral blindness; it accounted for blindness in 30% of all bilaterally blind persons.3 Amazingly, no cases of bilateral blindness in blacks were due to AMD. Not even a single eye was blind due to AMD in a bilaterally blind black person. Fun¬ dus photographs from the Baltimore Eye Survey currently are being read to determine if rates of precursor lesions, such as soft or confluent drusen and focal macular hyperpigmentation, are lower among blacks than among whites. For example, the earlier, nonexudative changes of AMD may be similarily prevalent in blacks and whites, even though choroidal neovascularization is much rarer in blacks. On this subject, previous data are sparse and some¬ what contradictory. In the Barbados Eye Study, Schachat et al4 found a prevalence of nonexudative AMD in blacks comparable with the rate in whites. Gregor and Joffe,5 comparing 1000 black South Afri¬ can patients with 380 whites from London, England, found that drusen and pigment epithelial changes were twice as common in whites as in black Afri¬ cans. They also noted that disciform degeneration was exceedingly rare in black Africans, seen in only 0.1% of this population compared with 3.5% of the whites. On the other hand, studies by Klein and Klein,6 using data from the National Health and Nu¬ trition Examination Survey, found no difference be-
Downloaded From: http://archopht.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/26/2015
tween whites and blacks in the percentage of pa¬ tients with "senile macular degeneration." Another analysis of these data came to the same conclusion.7 It is likely that the vast majority of these cases of macular degeneration in the National Health and Nutrition Examination Survey data were atrophie
macular degeneration, rather than choroidal neovascularization/disciform degeneration. For the patients with POHS, many clinicians also believe that disciform macular changes are much rarer in blacks with this syndrome than in whites.8 However, cases of choroidal neovascularization in these patients have been identified.8 The explanation for the apparent discrepancy in the prevalence of choroidal neovascularization in white and black patients with POHS and AMD re¬ mains uncertain. One possibility is that an increased amount of melanin in black patients' eyes is protec¬ tive. This melanin could act as a free radical scaven¬ ger, or in some other way protect the pigment epi¬ thelium, Bruch's membrane, choroid, or outer retina from degenerative changes predisposing the patient to choroidal neovascularization. The pigment or other factors in the darkly pigmented retinal pig¬ ment epithelium or choroid may have an inhibitory effect on leakage, migration, or proliferation of en¬ dothelial cells. To investigate the role of pigment, it is important to determine whether there is indeed a difference in atrophie AMD between black and white patients. The prevalence of choroidal neovasculariza¬ tion in darkly pigmented, non-African ethnic groups (eg, East Indians) should be studied. Ethnic groups with intermediate pigmentation (eg, Orientals) should be studied also. Other possible explanations include population dif¬ ferences in the frequency of human leukocyte antigen
Currently
or in other genetic modifiers predisposing pa¬ tients to or protecting patients from AMD and POHS. Since there has been considerable mixing of black and white genes in the US black population, such explana¬ tions for the very low incidence of choroidal neovascu¬ larization from AMD in blacks seem unlikely. Even less likely explanations might include environmental fac¬ tors like socioeconomic status, or systemic factors like blood pressure. Choroidal neovascularization from AMD is appar¬ ently almost nonexistent in black patients. It is also rare in black patients with POHS. The explanation for its absence remains unknown, and further study is clearly needed.
types
Lee M. Jampol, MD Chicago, Ill James Tielsch, PhD Baltimore, Md References 1. Jampol LM. Hypertension and visual outcome in the Macular Photocoagulation Study. Arch Ophthalmol. 1991;109:789-790. 2. Tielsch JM, Sommer A, Witt K, Katz J, Royall RM, the Baltimore Eye Survey Research Group. Blindness and visual impairment in an American urban population: the Baltimore Eye Survey. Arch Ophthalmol. 1990;108:286\x=req-\ 290. 3. Sommer A, Tielsch JM, Ratz J, et al. Racial differences in the causespecific prevalence of blindness in east Baltimore. N Engl J Med. 1991;325: 1412-1417. 4. Schachat AP, Hyman L, Leske MC, et al. Prevalence of macular degeneration in a black population. Invest Ophthalmol Vis Sci. 1992;33(suppl):801. 5. Gregor Z, Joffe L. Senile macular changes in the black African. Br J Ophthalmol. 1978;62:547-550. 6. Klein BE, Klein R. Cataracts and macular degeneration in older Americans. Arch Ophthalmol. 1982;100:571-573. 7. Goldberg J, Flowerdew G, Smith E, Brody JA, Tso MOM. Factors associated with age-related macular degeneration: an analysis of data from the first National Health and Nutrition Examination Survey. Am J Epidemiol. 1988; 128:700-710. 8. Baskin MA, Jampol LM, Huamonte FA, Rabb MF, Vygantas CM, Wyhinny G. Macular lesions in blacks with the presumed ocular histoplasmosis syndrome. Am J Ophthalmol. 1980;89:77-83.
in Other AMA Journals
ARCHIVES OF NEUROLOGY
Agraphia in Dementia of the Alzheimer Type Emily LaBarge, EdD; Deborah S. Smith, PhD; Leah Dick, MA; Martha Storandt, PhD (Arch Neurol. 1992;49:1151-1156) Neurologic and Neuropsychological Manifestations of Human Immunodeficiency Virus Infection in Intravenous Drug Users Without Acquired Immunodeficiency Syndrome: Relationship to Head Injury Karen Marder, MD, MPH; Yaakov Stern, PhD; Renee Malouf, MD; Ming-Xin Tang, PhD; Karen Bell, MD; George Dooneief, MD; Waafa El-Sadr, MD; Scott Goldstein, MA; Jack Gorman, MD; Marcus Richards, PhD; Mary Sano, PhD; Stephan Sorrell, MD; George Todak, MSW; Janet B. W. Williams, DSW; Anke Ehrhardt, PhD; Richard Mayeux, MD (Arch Neurol. 1992;49:1169-1175)
Downloaded From: http://archopht.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/26/2015
Photocoagulation Study
Macular Photocoagulation Study (MPS) is The multicenter, collaborative, clinical trial that vides for the of choroi-
a
important guidelines
treatment
pro-
age-related macular degeneration (AMD), presumed ocular histoplasmosis syndrome (POHS), and idiopathic neovascularization. In a previous editorial, Jampol1 discussed the role of hypertension among patients in the MPS, showing that under some circumstances, patients with hypertension had a less beneficial response to laser photocoagulation. dal neovascularization from
Another aspect of the MPS that has received almost no attention to date is the racial characteristics of patients enrolled in the trial. See also p 1701.
The MPS includes three clinical trials for AMD:
argon-laser photocoagulation for extrafoveal membranes, krypton-laser photocoagulation for juxtafoveal membranes, and argon or krypton laser photocoagulation for subfoveal membranes. As of July 1,1991, a total of 1319 patients had been enrolled in these trials (Maureen Maguire, PhD, written communication). Of these patients, 1314 were white, one was black, and four
were
listed
as
"other." This leads to
an
astonish¬
ing statistic: only 0.08% of the patients were black. Al¬ though arguments can be made that blacks, due to eco¬ nomic, cultural, geographic, or other reasons, might be less likely to enroll in a randomized trial, other oph¬ thalmic clinical trials performed at similar academic institutions across the country have had a much higher percentage of black participants. For example, the Di¬ abetic Retinopathy Study had 5.9% black patients, the Early Treatment Diabetic Study had 13.6%, the Dia¬ betic Retinopathy Vitrectomy Study had 12.1%, and the Collaborative Corneal Transplantation Studies had 15.5%. We have not quoted percentages from analogous studies of ocular melanoma or glaucoma, because
blacks are believed to have a decreased incidence of choroidal melanoma and an increased incidence of open angle glaucoma. The prevalence of a racial group within the enrollees of a randomized study certainly does not represent their prevalence in the total population at risk, but the MPS data indicate that choroidal neovas¬ cularization from AMD is extremely rare in blacks. Similar clinical trials have also been performed in the
MPS on patients with POHS: argon laser for ex¬ trafoveal membranes, and krypton laser for jux¬ tafoveal membranes. Smaller trials have been per¬ formed on patients with idiopathic neovascularization. As of July 1, 1991, a total of 667 patients had been en¬ rolled in these various trials. Sixteen patients (2.4%) were black. By combining AMD, POHS, and idiopathic neovasculariaztion, a total of 1986 patients had been enrolled, and just 17 (0.9%) were black. Many clinicians believe that disciform macular de¬ generation with choroidal neovascularization is much rarer in blacks, with a variety of causes, including AMD, ocular histoplasmosis, and perhaps other dis¬ eases, such as angioid streaks. Until recently there were relatively few studies in this area. In the Bal¬ timore Eye Survey,2 among 5308 persons 40 years of age and older participating in this population-based sample, blacks had more than twice the age-adjusted rate of legal blindness as did whites (1.75% as op¬ posed to 0.76%). Among whites, AMD was the lead¬ ing cause of bilateral blindness; it accounted for blindness in 30% of all bilaterally blind persons.3 Amazingly, no cases of bilateral blindness in blacks were due to AMD. Not even a single eye was blind due to AMD in a bilaterally blind black person. Fun¬ dus photographs from the Baltimore Eye Survey currently are being read to determine if rates of precursor lesions, such as soft or confluent drusen and focal macular hyperpigmentation, are lower among blacks than among whites. For example, the earlier, nonexudative changes of AMD may be similarily prevalent in blacks and whites, even though choroidal neovascularization is much rarer in blacks. On this subject, previous data are sparse and some¬ what contradictory. In the Barbados Eye Study, Schachat et al4 found a prevalence of nonexudative AMD in blacks comparable with the rate in whites. Gregor and Joffe,5 comparing 1000 black South Afri¬ can patients with 380 whites from London, England, found that drusen and pigment epithelial changes were twice as common in whites as in black Afri¬ cans. They also noted that disciform degeneration was exceedingly rare in black Africans, seen in only 0.1% of this population compared with 3.5% of the whites. On the other hand, studies by Klein and Klein,6 using data from the National Health and Nu¬ trition Examination Survey, found no difference be-
Downloaded From: http://archopht.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/26/2015
tween whites and blacks in the percentage of pa¬ tients with "senile macular degeneration." Another analysis of these data came to the same conclusion.7 It is likely that the vast majority of these cases of macular degeneration in the National Health and Nutrition Examination Survey data were atrophie
macular degeneration, rather than choroidal neovascularization/disciform degeneration. For the patients with POHS, many clinicians also believe that disciform macular changes are much rarer in blacks with this syndrome than in whites.8 However, cases of choroidal neovascularization in these patients have been identified.8 The explanation for the apparent discrepancy in the prevalence of choroidal neovascularization in white and black patients with POHS and AMD re¬ mains uncertain. One possibility is that an increased amount of melanin in black patients' eyes is protec¬ tive. This melanin could act as a free radical scaven¬ ger, or in some other way protect the pigment epi¬ thelium, Bruch's membrane, choroid, or outer retina from degenerative changes predisposing the patient to choroidal neovascularization. The pigment or other factors in the darkly pigmented retinal pig¬ ment epithelium or choroid may have an inhibitory effect on leakage, migration, or proliferation of en¬ dothelial cells. To investigate the role of pigment, it is important to determine whether there is indeed a difference in atrophie AMD between black and white patients. The prevalence of choroidal neovasculariza¬ tion in darkly pigmented, non-African ethnic groups (eg, East Indians) should be studied. Ethnic groups with intermediate pigmentation (eg, Orientals) should be studied also. Other possible explanations include population dif¬ ferences in the frequency of human leukocyte antigen
Currently
or in other genetic modifiers predisposing pa¬ tients to or protecting patients from AMD and POHS. Since there has been considerable mixing of black and white genes in the US black population, such explana¬ tions for the very low incidence of choroidal neovascu¬ larization from AMD in blacks seem unlikely. Even less likely explanations might include environmental fac¬ tors like socioeconomic status, or systemic factors like blood pressure. Choroidal neovascularization from AMD is appar¬ ently almost nonexistent in black patients. It is also rare in black patients with POHS. The explanation for its absence remains unknown, and further study is clearly needed.
types
Lee M. Jampol, MD Chicago, Ill James Tielsch, PhD Baltimore, Md References 1. Jampol LM. Hypertension and visual outcome in the Macular Photocoagulation Study. Arch Ophthalmol. 1991;109:789-790. 2. Tielsch JM, Sommer A, Witt K, Katz J, Royall RM, the Baltimore Eye Survey Research Group. Blindness and visual impairment in an American urban population: the Baltimore Eye Survey. Arch Ophthalmol. 1990;108:286\x=req-\ 290. 3. Sommer A, Tielsch JM, Ratz J, et al. Racial differences in the causespecific prevalence of blindness in east Baltimore. N Engl J Med. 1991;325: 1412-1417. 4. Schachat AP, Hyman L, Leske MC, et al. Prevalence of macular degeneration in a black population. Invest Ophthalmol Vis Sci. 1992;33(suppl):801. 5. Gregor Z, Joffe L. Senile macular changes in the black African. Br J Ophthalmol. 1978;62:547-550. 6. Klein BE, Klein R. Cataracts and macular degeneration in older Americans. Arch Ophthalmol. 1982;100:571-573. 7. Goldberg J, Flowerdew G, Smith E, Brody JA, Tso MOM. Factors associated with age-related macular degeneration: an analysis of data from the first National Health and Nutrition Examination Survey. Am J Epidemiol. 1988; 128:700-710. 8. Baskin MA, Jampol LM, Huamonte FA, Rabb MF, Vygantas CM, Wyhinny G. Macular lesions in blacks with the presumed ocular histoplasmosis syndrome. Am J Ophthalmol. 1980;89:77-83.
in Other AMA Journals
ARCHIVES OF NEUROLOGY
Agraphia in Dementia of the Alzheimer Type Emily LaBarge, EdD; Deborah S. Smith, PhD; Leah Dick, MA; Martha Storandt, PhD (Arch Neurol. 1992;49:1151-1156) Neurologic and Neuropsychological Manifestations of Human Immunodeficiency Virus Infection in Intravenous Drug Users Without Acquired Immunodeficiency Syndrome: Relationship to Head Injury Karen Marder, MD, MPH; Yaakov Stern, PhD; Renee Malouf, MD; Ming-Xin Tang, PhD; Karen Bell, MD; George Dooneief, MD; Waafa El-Sadr, MD; Scott Goldstein, MA; Jack Gorman, MD; Marcus Richards, PhD; Mary Sano, PhD; Stephan Sorrell, MD; George Todak, MSW; Janet B. W. Williams, DSW; Anke Ehrhardt, PhD; Richard Mayeux, MD (Arch Neurol. 1992;49:1169-1175)
Downloaded From: http://archopht.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/26/2015
