The cone degenerations

Summary

Retinal abnormalities characterized by a severe diffuse cone abnormality (as defined by the ERG) or by pronounced focal macular cone involvement (as defined by color vision testing) were discussed in this report. Data from 38 patients with diffuse cone abnormalities and seven patients who initially had only pronounced focal macular cone involvement were presented, and the previous literature in this area was reviewed.

Loss of visual acuity, photophobia, and defective color vision are the three major complaints of these patients. Loss of visual acuity usually precedes notable color blindness as a complaint. Side vision loss and nightblindness are extremely rare complaints, even in far advanced cases. These patients usually initially note symptoms during the first two decades of life; however, severe cone disease may begin at any age, even in the seventh decade.

Visual acuity loss is usually symmetrical, but occasionally may be quite asymmetrical. Typically, vision deteriorates to between 20/200 to 10/200 and remains stable at this level. Progression appears to occur more rapidly in patients with an earlier age of onset.

Cone degenerations may occur in patients with the typical eyeground changes of fundus flavimaculatus (9 of our 45 patients), or rarely in patients with eye-ground and functional changes of retinitis pigmentosa (1 of our 45 patients); however, most commonly cone degenerations are not associated with either condition.

Three types of macular lesions are seen in patients with cone degenerations and the most common type has a central non-involved area of pigment epithelium, giving a bull's-eye appearance. This bull's-eye type of lesion is often difficult to recognize in early stages on routine evaluation, but may be obvious on fluorescein angiography.

A second type of lesion consists of diffuse pigment clumping throughout the macular area and is associated with a much more widespread area of pigment epithelium involvement on fluorescein angiography. Typical discrete pigmentary deposits along the large retinal veins may be seen with this type of macular lesion. In the third, and rarest type of macular abnormality, there is discrete atrophy of the choroidal vascular elements within the lesion. These latter two types of macular lesions are usually associated with rod, as well as cone disease, and usually show fairly rapid progression of visual loss within the first or second decade of life.

Optic disc pallor, particularly of the temporal half, is a fairly common finding, and may be the earliest or occasionally the only eyeground abnormality seen. Attenuated retinal vessels and pigmentary deposits outside of the macula may be seen in some patients, usually with evidence of rod, as well as cone involvement.

Peripheral visual fields are usually intact, although paracentral and sometimes mid-peripheral partial ring scotomas are seen in more advanced cases. Relative central scotomas are, of course, universal, but more pronounced paracentral involvement may be noted, resulting in a doughnut-shaped scotoma with certain size targets.

Color vision usually becomes severely abnormal at visual acuity levels of 20/40 to 20/60. More severe color vision defects are typically seen than in other retinal and optic nerve diseases and, indeed, the findings may eventually be similar to those seen in congenital total color blindness. Typical defects on the Farnsworth-Munsell 100-hue test and Nagel anomaloscope usually delineate patients with cone degenerations, even in relatively early stages, from patients with other acquired color vision defects.

Final rod thresholds on dark-adaptation are usually normal or only mildly abnormal, even in far advanced cases, with severely abnormal electroretinographic findings. Abnormalities of the cone portion of the dark-adaptation curve, though, are common. A normal or abnormal electrooculogram may be seen in these patients (despite the absence or presence of rod involvement).

Abnormalities of the portions of the electroretinogram presumed to relate to cone function are diagnostic. Markedly abnormal single-flash photopic and flecker responses were most useful in evaluating these patients. However, abnormalities of high-intensity scotopic responses (thought to reflect both rod and cone function), and of the first portion of a high-intensity scotopic orange-red response (thought to reflect mainly cone function) are also common.

Abnormal rod function is diagnosed primarily by the ERG. With our technique, subnormal low-intensity scotopic responses, thought to relate only to rod function, were seen in such patients. However, even in these cases, final rod thresholds on dark adaptation were usually normal or only mildly abnormal.

The distinction between patients with only cone involvement and those with both rod and cone involvement has limited value, as both types of cases may be seen within the same family. Likewise, an individual may initially have only cone disease, but eventually may have rod involvement as well. Nevertheless, there may be families where only cone involvement occurs.

Regional distinctions are also made. Most commonly, there appears to be (as judged by the ERG and color vision) diffuse cone disease. On the other hand, patients with only central cone disease are occasionally seen who have severe color vision defects and a normal ERG. Or patients may be noted with a severe cone ERG abnormality and relatively poor acuity who have fairly good color vision. The designation ‘peripheral’ cone degeneration may be appropriate for these patients, but obviously, with visual acuity loss, there is some central cone involvement. Furthermore, some patients who initially have only ‘peripheral cone’ disease (as judged by color vision performance) may eventually show severe color vision abnormalities on follow-up.

Autosomal dominant inheritance is most common in familial cases, although autosomal recessive inheritance is seen, particularly in patients with eyeground changes of fundus flavimaculatus. Sporadic cases may occur secondary to toxins.

It is likely that cases previously reported in the past as total congenital color blindness with macular and/or optic nerve disease are really examples of cone degenerations. In our opinion, congenital total color blindness is not associated with eyeground changes. Similarly, cases reported in the past as retinitis pigmentosa with total color blindness are probably mostly examples of cone-rod degenerations. This latter category is easily distinguished from true retinitis pigmentosa (in spite of what may appear to be similar eyegrounds) by the usual retention of normal or close to normal dark adaptation. Occasionally, though, true retinitis pigmentosa may be characterized by the early occurrence of severe color blindness as well as night-blindness.