Vitamin A-Deficiency Eye Disease Among Soldiers in the U.S. Civil War: Spectrum of Clinical Disease.

During the U.S. Civil War, nutritional night blindness was a common problem among soldiers forced to subsist of nutritionally inadequate diets, but medical officers typically attributed this complaint to malingering and did not suspect or appreciate a dietary basis. More than 8,000 cases of night blindness were recorded among Union troops, but many cases were not tabulated because of incomplete data for black soldiers and prisoners of war. From 1864 to 1865, during which comparable data were available for both whites and blacks, the average annual cumulative incidence of night blindness was 4.3 per 1,000 troops for whites, compared with 11.0 per 1,000 troops for blacks. Affected patients had dilated pupils that were poorly responsive to candle light. Approximately 30 cases of keratomalacia were also reported among severely malnourished and emaciated soldiers with chronic diarrhea, generally within 2 weeks before death. The reported clinical manifestations are characteristic of the full range of vitamin A deficiency eye disease from night blindness to corneal ulceration and perforation. Although medical officers typically accused affected soldiers of malingering, malingering cannot account for either the observed abnormalities of pupillary reflexes, or the corneal epithelial pathology and mortality recorded in severe cases.

Seasonal variation in night blindness incidence among Union soldiers in the US Civil War.

BACKGROUND: During the US Civil War, medical officers typically attributed night blindness among soldiers to malingering. A dietary basis was not generally suspected or appreciated. DESIGN/METHODS: Incident cases of night blindness, scurvy, and diarrheal diseases, as well as mean troop strength among Union troops, were abstracted by month and race from tabulations of the US Surgeon General for the period from July 1861 through June 1866. Monthly incidence rates and annual incidence rates are presented as time series by race. RESULTS: Night blindness incidence was seasonal. Seasonal patterns of night blindness incidence were similar for white and black soldiers, although the peak incidence rates were approximately 2-3 times higher in black soldiers. The seasonal effect for white Union soldiers increased progressively to 1864. The seasonal pattern for night blindness roughly parallels that for scurvy and for diarrheal diseases. The peak season for night blindness incidence was summer, and the next highest season was spring. The mode of monthly incidence rates for diarrheal diseases slightly anticipated that for night blindness and scurvy. In addition, there was greater relative variation in monthly incidence for night blindness and scurvy than for diarrheal diseases. CONCLUSIONS: Nutritional night blindness occurred in a seasonal pattern among soldiers forced to subsist on nutritionally inadequate diets. The seasonal pattern is consistent with seasonal variations in the availability of foodstuffs with high vitamin A or provitamin A content, superimposed on marginal vitamin A reserves, and possibly exacerbated by co-occurring seasonal patterns of diarrheal disease.

A historical perspective on the early treatment of night blindness and the use of dubious and unproven treatment strategies for patients with retinitis pigmentosa.

Retinitis pigmentosa (RP) is a form of inherited night blindness. Over decades, various dubious treatment strategies that lacked sufficient theoretically sound underpinnings were explored. Initially they were enthusiastically promoted and subsequently discredited. It is apparent that many were predicated on the erroneous assumption that the primary cause of RP was related to impairment of the retinal circulation. Herein, several of these strategies are reviewed and critiqued. Reasons why clinicians may have been deceived into overzealous interpretations of their treatment methods are explored. The examples disclosed should serve as a note of caution for current investigators to guard against self-deception when exploring newly developed treatment strategies.

Chapter 29: historical aspects of the major neurological vitamin deficiency disorders: overview and fat-soluble vitamin A.

The vitamine doctrine: Although diseases resulting from vitamin deficiencies have been known for millennia, such disorders were generally attributed to toxic or infectious causes until the "vitamin doctrine" was developed in the early 20th century. In the late-19th century, a physiologically complete diet was believed to require only sufficient proteins, carbohydrates, fats, inorganic salts, and water. From 1880-1912, Lunin, Pekelharing, and Hopkins found that animals fed purified mixtures of known food components failed to grow or even lost weight and died, unless the diet was supplemented with small amounts of milk, suggesting that "accessory food factors" are required in trace amounts for normal growth. By this time, Funk suggested that deficiencies of trace dietary factors, which he labeled "vitamines" on the mistaken notion that they were "vital amines," were responsible for such diseases as beriberi, scurvy, rickets, and pellagra. Vitamin A deficiency eye disease: Night blindness was recognized by the ancient Egyptians and Greeks, and many authorities from Galen onward advocated liver as a curative. Outbreaks of night blindness were linked to nutritional causes in the 18th and 19th centuries by von Bergen, Schwarz, and others. Corneal ulceration was reported in 1817 by Magendie among vitamin A-deficient dogs fed for several weeks on a diet limited to sugar and water, although he erroneously attributed this to a deficiency of dietary nitrogen (i.e. protein). Subsequently, corneal epithelial defects, often in association with night blindness, were recognized in malnourished individuals subsisting on diets now recognizable as deficient in vitamin A by Budd, Livingstone, von Hubbenet, Bitot, Mori, Ishihari, and others. During World War I, Bloch conducted a controlled clinical trial of different diets among malnourished Danish children with night blindness and keratomalacia and concluded that whole milk, butter, and cod-liver oil contain a fat-soluble substance that protects against xerophthalmia. Early retinal photochemistry: In the 1870s, Boll found that light causes bleaching of the retinal pigment, and suggested that the outer segments of the rods contain a substance that conveys an impression of light to the brain by a photochemical process. Shortly thereafter, Kühne demonstrated that the bleaching process depends upon light, and was reversible if the retinal pigment epithelium was intact. Kühne proposed an "optochemical hypothesis," a prescient concept of photochemical transduction, attributing vision to a photochemical change in visual purple (rhodopsin) with resulting chemical products stimulating the visual cells and thereby conveying a visual image. Vitamin A: In 1913, Ishihara proposed that a "fatty substance" in blood is necessary for synthesis of both rhodopsin and the surface layer of the cornea, and that night blindness and keratomalacia develop when this substance is deficient. That year McCollum and Davis (and almost simultaneously Mendel and Osborne) discovered a fat-soluble accessory food factor (later called "fat-soluble A") distinct from the water-soluble anti-beriberi factor (later called "fat-soluble B"). By 1922 McCollum and colleagues distinguished two vitamins within the fat-soluble fraction, later named vitamins A and D. In 1925 Fridericia and Holm directly linked vitamin A to night blindness in animal experiments using rats, and in 1929 Holm demonstrated the presence of vitamin A in retinal tissue. In the 1930s, Moore, Karrer, Wald, and others established the provitamin role of beta-carotene. Karrer and colleagues isolated beta-carotene (the main dietary precursor of vitamin A) and retinol (vitamin A), and determined their chemical structures. In 1947, Isler and colleagues completed the full chemical synthesis of vitamin A. Modern retinal photochemistry: Beginning in the 1930s, Wald and colleagues greatly elaborated the photochemistry of vision, with the discovery of the visual cycle of vitamin A, demonstration that rhodopsin is decomposed by light into retinal (the aldehyde form of vitamin A) and a protein (opsin), elaboration of the enzymatic conversions of various elements in the rhodopsin system, and discovery that the rhodopsin system is dependent on a photoisomerization of retinal. In 1942, Hecht and colleagues demonstrated that a single photon could trigger excitation in a rod. In 1965, Wald suggested that a large chemical amplification was necessary for this degree of light sensitivity, likely by a cascade of enzymatic reactions. Later studies elaborated this cascade and found that an intermediary in the photoisomerization of retinal interacts with transducin, a G-protein, to activate phosphodiesterases that control cyclic GMP levels, which in turn modulate the release of neurotransmitter from the rod cell. Public health: Although the availability of vitamin A through food fortification and medicinal supplements virtually eliminated ocular vitamin A deficiency from developed countries by the second half of the 20th century, vitamin A deficiency remains a serious problem in developing countries as indicated by global surveys beginning in the 1960s. Millions of children were shown to be vitamin A deficient, with resultant blindness, increased susceptibility to infection, and increased childhood mortality. Beginning in the 1960s, intervention trials showed that vitamin A deficiency disorders could be prevented in developing countries with periodic vitamin A dosing, and in the 1980s and 1990s, large randomized, double-blind, placebo-controlled clinical trials demonstrated the marked efficacy of vitamin A supplementation in reducing childhood mortality.

Nyctalopia in antiquity: a review of the ancient Greek, Latin, and Byzantine literature.

OBJECTIVE: To investigate the original definition and use of the term nyctalopia in ancient medical literature in view of the controversy between the English and some continental European literatures. DESIGN: Historical manuscript. METHODS: We review the use of the term in ancient Greek, Roman, and early Byzantine medical literature (5th century BC-7th century AD) and include a quick reference to the theories on its etymology. RESULTS: Physicians of antiquity defined as nyctalopia the symptom of defective dark adaptation, most commonly in the clinical setting of vitamin A deficiency. An alternative definition, the improvement of vision at night, is not recorded before the 2nd century AD and seems to result from a broader interpretation of the word, lacking medical acceptance at that time. CONCLUSIONS: We propose to the ophthalmic community the use of the term nyctalopia exclusively for the description of defective dark adaptation.

Eduard Schwarz, a neglected pioneer in the history of nutrition.

An account of the journey around the world by the Austrian ship's doctor Eduard Schwarz on a sailing ship from 1857 to 1859, his successful cure of nightblindness among the sailors, and how he was maligned by some of the Viennese medical press for his view that nightblindness is a nutritional disorder.

[Historical milestones in the treatment of night blindness]. / Geschichtliche Meilensteine in der Behandlung der Nachtblindheit.

Most cases of night-blindness (nyctalopia or hemeralopia) do occur without an apparent organic eye-disease. In the past one spoke of essential or epidemic night-blindness. It is caused by a vitamin deficiency, and is a result of failing dark adaptation; it may lead to xerophthalmia, and finally to a complete permanent blindness, if not treated in time with vitamin A or vitamin A containing food (butter, egg-yolk, fish-liver oil). From time immemorial the healing effects of the intake of liver from fish and various animals for night-blindness has been reported from countries all over the world. In medical literature it has been recommended in the Papyrus Ebers (ca. 1500 B.C.), by the old Greek writers, from Hippocrates to Galen, and later to Oribasius and others. In the early sixteenth century Jac. Bontius (1592-1631) learned this therapy from empiric folk-medicine and advocated shark-liver as a specific medicine. Notwithstanding scattered reports of the dramatic favourable result of liver-treatment in patients with night-blindness, it would last until experimental research with a fat-poor diet led to the discovery (1913) and identification of vitamin A in our century, and the high vitamin A content of liver was established. Thus recognizing the value of the old liver-treatment, finally vitamin A was introduced in official ophthalmology. So an age-old, nearly universal favourable experience of empiric medicine had been neglected to the detriment of countless sufferers of night-blindness. Today systematic administration in cases of impending blindness, especially in some Asiatic areas, has already prevented the development of lasting blindness on a large scale.

The Eisdell pedigree. Congenital stationary night-blindness with myopia.

A pedigree of X-linked congenital stationary night-blindness, originally published by Nettleship, is presented with abstracts from his private correspondence. An affected descendant has supplied letters and the original working pedigree which led to the publication of the extended pedigree in 1912.