Cone Dysfunction Syndromes, Cone Dystrophies, and Cone-Rod Degenerations

Abstract Predominant abnormalities of cone photoreceptor function are present in retinal disorders previously classified under a number of headings, such as cone dystrophies, cone-rod degenerations, color blindness, complete and incomplete achromatopsia, some types of retinitis pigmentosa, Stargardt disease, and many inherited systemic diseases with retinal degeneration. In this chapter we will try to clarify the classification of disorders that predominantly or primarily affect cones and either involve the eye alone or occur in the context of systemic diseases. The term “cone dysfunction syndromes” refers to disorders that are predominantly stationary while cone dystrophies and cone–rod degenerations involve progressive loss of cone function and generalized retinal degeneration with (in the latter) or without (in the former) subsequent signs and symptoms of rod dysfunction (Table 26.1).1 Stationary disorders include normal variations in color vision, anomalous trichromacy, dichromacy complete and incomplete achromatopsia, rod monochromacy, oligocone trichromacy, and bradyopsia. Although blue cone monochromacy was initially thought to be a stationary disorder, patients develop progressive macular degeneration and atrophy in middle and old age (Fig. 26.1).2 The stationary cone dysfunction syndromes (Table 26.2) are for the most part covered in chapter 36. A section on oligocone trichromacy and bradyopsia is included in this chapter. Cone dystrophies are characterized by the clinical triad of photodysphoria, abnormal color vision or dyschromatopsia, and reduced central vision, with or without nystagmus. Cone dystrophies overlap to some extent with cone–rod degenerations in which rod dysfunction is added to that of cones. One less well-defined group of cone disorders includes benign concentric annular dystrophy, cone dystrophy with supernormal ERG, and occult macular degeneration. We have classified them under the cone dystrophies since they show signs and symptoms of progressive cone dysfunction. Cone–rod degenerations are varied, and most or the genes that cause these autosomal dominant, recessive, and X-linked disorders have been identified (Table 26.3). Cone–rod degeneration also occurs in a number of systemic conditions, such as the Bardet-Biedl syndromes, fucosidosis, neuronal ceroid lipofuscinosis, infantile phytanic acid storage disease, and methylmalonic aciduria with homocystinuria, among other rare inherited diseases. Finally, toxicity from some medications, such as digoxin and chloroquine, may result in macular degeneration and cone dysfunction. Toxic retinopathies are not discussed in this textbook. Many of the inherited disorders in Table 26.1 are covered in chapter 36 and the reader is referred to the respective chapters for more information.