Ординатура / Офтальмология / Английские материалы / Handbook of Nutrition and Ophthalmology_Semba_2007

reported in Adek, Log, and Banjoebiroe camps, where polished rice was the main dietary staple (293). In Tjimaji camp, Java, nutritional amblyopia was reported among 7–8% of the internees (260). One physician found that thiamin treatment was effective in treating nutritional amblyopia (294).

Middle East. Nutritional amblyopia was described among 112 German prisoners of war who were held captive in Egypt, and associated findings included ataxia (21%), nerve deafness (11%) and both ataxia and nerve deafness (8%) (295). The cases occurred in a camp of about 10,000 men where diarrhea, dysentery, malnutrition, pellagra, ariboflavinosis, and scurvy were common. Although the recommended diet for the camp was supposed to consist of 3574 calories per day, with sufficient B complex vitamins, the actual conditions were far different because of wartime conditions and shortages (295). Nine cases of nutritional amblyopia were described among German soldiers held prisoners of war by the British in the Mediterranean region (296). Associated findings included burning feet, tinnitus and deafness, hoarseness, weakness in the legs, and dermatitis consistent with pellagra (296).

Europe. Although there were thousands of prisoners of war and civilian prisoners held in different camps in Europe and Russia during World War II, there were only relatively rare reports of nutritional amblyopia compared with southeast Asia and the Middle East. This led some to speculate that the tropical heat or excessive sunlight were a predisposing factor that could explain the high incidence of the disease in the tropics (260). Such climatic and environmental factors do not explain the cases of nutritional amblyopia reported during World War I and the Spanish Civil War (259). After World War II, Berlin became a transit center for Eastern refugees and prisoners of war, and some cases were described among prisoners returning from Russia (297). Other cases were described among the civilian population of Berlin, which was subjected to poor dietary conditions in the latter part of the war (297). Clinical examination of thousands of Poles who were released from Russian concentration camps in 1943 did not reveal any cases of nutritional amblyopia (298). Although the internees received a poor diet, the main staple was black bread, 450– 500 g a day, which would provide 1.03–1.15 mg of thiamin per day, close to the current RDA for thiamin.

Korean War. Nutritional amblyopia also affected American servicemen who were held prisoner of war in North Korea (299). A total of 3745 Americans held prisoner of war were repatriated from prison camps in Korea. In spring of 1953, during “Operation Little Switch,” 149 of the most seriously ill prisoners were released. The remaining prisoners were released in August and Septmber 1953 in “Operation Big Switch” after hostilities had ceased. Twenty-two men were found to have nutritional amblyopia, and common associated findings were beriberi, diarrhea, dysentery, peripheral neuropathy, and night blindness. Four of the patients had hearing loss (299).

Vietnam War. In the Repatriated Prisoners of War program, American servicemen were seen after being released from North Vietnam (170). Most of the prisoners of war at that time were aviators who had been shot down and were not ground troops. Of 332 servicemen seen, there were 3 cases of nutritional amblyopia. All three men had been captured in the period from 1963 to 1967, and the diet consisted mostly of turnip soup, potato soup, and no fats. After 1968, vitamins arrived from the Red Cross for the entire population of prisoners in North Vietnam, and no further cases of nutritional amblyopia were seen (170).

6.6.4. ETIOLOGY AND TREATMENT

Nutritional amblyopia among prisoners of war and civilians during times of war is largely consistent with that described in outbreaks of beriberi and pellagra (263,300). In the prison camps, the physicians usually treated the patients with yeast, marmite, B complex vitamins, thiamin alone, niacin alone, thiamin and niacin together, eggs, larger rations, rice polishings, local legumes, and any other vitamins they could find under conditions of extreme scarcity. Good responses to therapy were often described with most of these different treatments. From these reports, it is difficult to evaluate the relative efficacy of the treatments, as these were not controlled studies. In many cases, the physicians ran out of vitamins, and often they did not distinguish between treatment of acute cases, which would be expected to recovery quickly, and longstanding cases, which would not be expected to respond much to treatment. There is an anecdotal report of 70 hospital staff members who took daily thiamin as prophylaxis during a widespread outbreak of nutritional amblyopia in the prison camp and did not develop the disease (278), but there is another report where nutritional amblyopia developed among prisoners on thiamin treatment for beriberi (277).

There can be no doubt that the diets of the prison camps were insufficient in calories, proteins, fats, and most B complex vitamins (301–304). There are well documented outbreaks of beriberi, pellagra, scurvy, ariboflavinosis, and night blindness in many different prison camps (305). Although there were limited rations in the camps, the survival of many prisoners often depended on on their ability to purchase extra food on the black market and from local people who came to the camps (306). The provision of vitamins and extra rations from the International Red Cross were also thought to have made a difference in the long-term health of the prisoners (307). The reports of nutritional amblyopia during times of war are summarized in Table 10.

6.7. Case Study: The Cuban Neuropathy Epidemic

6.7.1. INTRODUCTION

In November 1991, several middle-aged men with loss of vision were seen at the Abel Santamaría Hospital in Pinar del Río, the westernmost province of Cuba (308). The men were diagnosed as having retrobulbar optic neuritis. In the ensuing months, about 14 to 36 new cases began to appear each month, and by July 1992, 168 cases had accumulated. In August 1992, 22 inmates from Ariza Prison in Cienfuegos were admitted to Aldereguía Provincial Hospital with edema, painful dysesthesias of the feet and legs, difficulty ambulating, sensory ataxia, and weakness. The patients were thought to have beriberi, and they responded to treatment with a better diet, thiamin, and B complex vitamins. By the end of 1992, there were 472 cases identified, and by March 1993, there were 4461 cases in total (309) (Fig. 13).

A task force was organized to deal with the epidemic on March 20, 1993 (308). The group was chaired by Comandante Fidel Castro Ruz and coordinated by the Civil Defense for Disaster Relief, the Ministry of Public Health, and the Cuban Academy of Sciences (310). The epidemic was distributed across the entire island of Cuba (9) (Fig. 14). An islandwide effort began to identify cases and promote early treatment, using some 18,000 family doctors involved in the primary care system. An increase in reported cases continued, many patients having isolated neuropathies, neuropathies associated with optic neuropathy

Fig. 13. Profile of the epidemic (the Direction National de Estadisticas, MINSAP, Cuba). (From refs.

308,309.)

Fig. 14. Incidence rate of neuropathy, by geographic region. (From ref. 9.)

and/or deafness. In early June 1993 there was a large decline in the incidence of cases which coincided with distribution of multivitamin supplements to the entire population of Cuba. Distribution of the vitamins began in May 1993. By January 14, 1994, there was an official tally of 50,862 cases. The history of the epidemic has been summarized elsewhere (308,310,311).

6.7.2. EPIDEMIOLOGY

The cases were classified as having either an optic or peripheral form, although combined forms of the disease were common. Eighty-seven percent of the cases occurred in adults between 25 and 64 yr of age, and the individuals at the lowest risk were children <15 yr, pregnant women, and adults >65 yr old. The national cumulative incidence of all forms of neuropathy, optic and/or peripheral, was 461.4/100,000 persons (9). In total, the

Table 11

Relation of Dietary Intake of Various Nutrients and Cassava to the Risk of Optic Neuropathy

aThe odds ratio is for the highest quartile compared with the lowest quartile. From ref. 312.

Table 12

Relation of Various Types of Behavior and Circumstances to the Risk of Optic Neuropathy

Reprinted from ref. 312. Copyright © 1995, Massachusetts Medical Society. All rights reserved.

proportions who were considered to have primarily optic and peripheral forms of the disease were 52% and 48%, respectively (9). The lack of a strict case definition for neuropathy was seen as a limitation in the epidemiological investigations (311).

A case control study was conducted in Pinar del Río in September 1993 order to identify epidemiological risk factors for optic neuropathy (312). One hundred twenty-three patients with severe optic neuropathy were identified and matched to cases by sex, municipality, and age (within 5 yr). The risk of optic neuropathy was lower among in those who had higher intakes of energy, and as a proportion of total energy, animal protein, animal fat, methionine, riboflavin, pyridoxine, and vitamin B12 (312) (Table 11). Although the study did not assess nutritional status of thiamin, niacin, folic acid, vitamin B12, pyridoxine, or riboflavin using biochemical assays, serum measures of vitamin A, major dietary carotenoids, and selenium were assessed. Low serum lycopene, α-carotene, β-carotene, and selenium concentrations were associated with an increased risk of optic neuropathy. Various behavioral and circumstantial factors were also studied (312) (Table 12). Factors that appeared to protect against optic neuropathy were having relatives overseas, raising chickens at home, and eating frozen cassava. Going without lunch or breakfast during the

week or going whole days without food increased the risk of optic neuopathy. Tobacco use, particularly cigar smoking, and high cassava consumption, relative to total energy intake, were both associated with an increased risk of optic neuropathy.

Another case-control study by Mas Bermejo and colleagues (313) showed there was an increased risk of disease with smoking (odds ratio [OR] 4.9, 95% confidence interval [CI] 2.5–9.3), irregular diet or missing meals (OR 4.7, 95% CI 2.5–8.8), combined smoking and drinking history (OR 3.5, 95% CI 1.7–7.4), weight loss (OR 2.8, 95% CI 2.2–3.6), excessive sugar consumption (OR 2.7, 95% CI 2.0–3.7) and heavy drinking (OR 2.3 95% CI 1.0–5.4). Pesticide exposure and household contact were not associated with an increased risk of disease. Another case-control study from the Isle of Youth, Cuba involved 34 cases with bilateral optic neuropathy and 65 healthy controls matched by residential block and age (314). Risk factors that were associated with increased risk of optic neuropathy included weight loss in the last 12 mo and low body mass index. Dietary intake was assessed using a semiquantitative study of intake frequency, and the intake of calories and nutrients was lower and the consumption of alcohol was higher in cases than controls. Intake of all B complex vitamins (thiamin, riboflavin, pyridoxine, niacin, and folic acid) was significantly associated with eye disease. Foods that were protective against disease were tubers and starchy roots (>125 g/d), beans (>120 g/d), oil (>15 g/d), and meat products extended with soybean flour (>15 g/d). Smoking was associated with disease in univariate analysis, but when smoking and alcohol consumption were put in a multivariate analysis with protein, calorie, and nutrient intake, the effect of smoking and alcohol consumption became statistically nonsignificant. This study suggested that foods which contain cyanogenic glucosides, such as yuca (cassava), cabbage, and beans, are not associated with disease, and in fact, some of these were protective against disease.

6.7.3. CLINICAL ASPECTS

The optic neuropathy in the Cuban epidemic was characterized by slowly progressive loss of vision in both eyes, loss of red-green color vision, and sometimes photophobia, burning eyes, lacrimation, and retrobulbar pain (308). Bilateral central or cecocentral scotomas were present and the peripheral visual field was normal. In most cases the optic discs were normal, but 12% had slight hyperemia of optic nerve heads. Loss of nerve fibers in the maculopapillary bundle was a typical finding, and in the context of the Cuban epidemic, was considered pathognomonic (308,315) (Fig. 15). In advanced cases, bilateral temporal optic disc pallor occurred (316) (Fig. 16).

The other neurological findings included a peripheral neuropathy characterized by “burning feet,” tingling, and hyperesthesia of the feet and legs. Bilateral foot drop with a steppage gait and paralysis of hand dorsiflexors were not uncommon and were consistent with beriberi. A dorsolateral myeloneuropathy was evidenced by an increase in urinary frequency, impotence in males, weakness of the legs, and difficulty walking. Gait alterations and frequent falls were often present. Sensorineural deafness, tinnitus, were common. Rarely, there was horseness or dysphagia. In a group of 602 patients with optic neuropathy studied by Santiesteban and colleagues, about one-third presented with skin and mucous membrane lesions consistent with undernutrition, 32% had associated myeloneuropathy, and 21% had hearing deficits on audiometry (317). No fatal cases were reported in the epidemic (9,308). A study of sural nerve biopsies in affected patients showed axonal dystrophy with loss of myelinated nerve fibers, especially large caliber myelinated fibers (318).

Fig. 15. Loss of papillomacular bundle in a Cuban patient with nutritional amblyopia. (Reprinted from ref. 315. Copyright © 1994, American Medical Association. All rights reserved.)

Fig. 16. Bilateral temporal optic disc pallor. (Reprinted from ref. 316. Copyright © 1993, American Medical Association. All rights reserved.)

6.7.4. RESPONSE TO TREATMENT

Confirmed cases were hospitalized and treated with intravenous B-group vitamins and folic acid, and nearly all patients recovered. Less than 0.1% of patients were left with moderate to severe sequelae (308). Oral supplements of B-complex vitamins and vitamin A

were provided by the Cuban government through community-based family physicians to persons in Pinar del Río province in March 1993 and to persons in other provinces starting in May 1993. The incidence of cases decreased during May–June 1993. For patients with optic neuropathy, the vitamin treatment resulted in marked improvement of visual acuity and color vision, except in patients who had a long delay in time of onset of symptoms to vitamin treatment.

6.7.5. INVESTIGATIONS OF OTHER CAUSES OF THE EPIDEMIC

A toxin hypothesis was “vigorously pursued” during initial investigations of the Cuban epidemic (308). Home brewed rum, contaminated tobacco, bush tea, insecticides, dietary cyanogens in cassava, and toxic legumes were among the suspected sources of toxins that could cause the epidemic (308). No toxins were identified, and the epidemiological profile of the outbreak did not fit the toxin theory. It made little sense that home brewed rum, made in thousands of different households with limited distribution, would suddenly appear in epidemic form across the entire island. Many affected individuals did not drink alcohol. Although smokers were at higher risk of optic neuropathy, the disease occurred among nonsmokers as well. Other food products, such as bush tea and cassava, were also made produced locally with limited distribution. The only common vehicle for a toxin was edible oil and flour, and these products did not come from a single point source, but rather from many different countries (319). The pattern in an epidemic caused by a toxin in food would show clustering in families and involvement of children, and this did not occur (319). It was even speculated that contaminated poultry feed with antimetabolites such as amprolium could have entered the food supply and caused the outbreak (320). If this were the cause of the epidemic, then the epidemiological pattern would have been the opposite, with children, pregnant women, and adults >65 yr old affected, because individuals in these groups had better access to animal protein such as chicken and eggs during the outbreak.

A genetic hypothesis was also investigated during the Cuban epidemic. The clinical presentation of reduced vision, central or cecocentral scotomas, occasional disc hyperemia, and later, bilateral temporal disc pallor, are also similar to that found in Leber hereditary optic neuropathy. Some affected patients were screened for mitochondrial DNA mutations associated with Leber hereditary optic neuropathy, but these studies did not show any association (321–323). The epidemiological profile of a widespread epidemic in Cuba is not consistent with that expected in a relatively rare genetic condition.

6.7.6. THE SOCIAL AND DIETARY SITUATION

The social and economic situation in Cuba in the period prior and during the epidemic was influenced both by the collapse of the Soviet Union and an economic embargo by the United States (308,324). A recent hurricane had also destroyed the already compromised food crops (325). Food and oil imports were in short supply, and there was a shortage of meat, pork, chicken, fish, eggs, dairy products, and vegetable oil (308). Food rationing was implemented by the Cuban government, but children, pregnant women, and adults >65 yr old received a larger ration of milk and eggs (316).

Nutritional studies conducted during and following the epidemic demonstrate that the Cuban population is highly vulnerable to some dietary deficiencies, such as that for thiamin, riboflavin, niacin, and vitamin B12 (308,312,327–330). Jimenez and colleagues measured vitamin levels in 105 patients with several forms of the disease and asymptomatic