The standardized electroretinogram (ERG) is the main clinical test that will confirm a cone degeneration or dystrophy. Cone degeneration or dysfunction may be congenital or acquired, but the diagnosis is often difficult to make, since the early fundus changes can be subtle. A standardized protocol with carefully established normal values is essential for optimally recognizing a cone dysfunction pattern. The clinician may have minimal physical evidence to motivate asking for an ERG or even, if suspicious, might not realize that the ERG is the definitive diagnostic test. Traditionally, cone dystrophy refers to congenital or very early onset cases, usually called achromatopsia, and cases with family inheritance patterns. The term cone degeneration is often used in acquired cases in which there is no family history.

Depending on the stage of disease and genetic type of cone disorder, clinical signs and fundus changes provide strong diagnostic clues that a cone disorder may be present. Patients with cone dysfunction typically complain of light sensitivity and tend to see better at dusk or in the dark.³ Most have uncorrectable subnormal vision, dark-to-light adaptation problems, and loss of hues or color blindness (variable finding). Frequently, patients do not volunteer these symptoms unless questioned directly for them. Some patients who are city dwellers will have “urban night blindness,” since at night, their cones do not function well in semilighted city areas where it is not dark enough for rods to be effective.

Common fundus findings include a circumscribed granularity or atrophy of the macular area and temporal optic pallor or atrophy. Congenital or early-onset cases will typically have nystagmus, which is often the symptom that brings the child to the eye doctor. Some X-linked cone dystrophy patients have confluent retinal areas of tapetal-like sheen (figure 70.1A and 70.1B), and rare patients have crystalline deposits in the macular area (figure 70.2). Krill reported a group of patients who had abnormal retinal blood vessel formation with cone dystrophy, including cases in which the retinal vessels crossed the raphe in the macula (figure 70.3).^6,8

Figure 70.1.  

Symmetric, round atrophy of fovea centralis is typically seen in a number of types of cone dystrophy or degeneration. A, In this case of X-linked cone dystrophy with tapetal sheen, the atrophy of the foveal centralis is highlighted by the surrounding sheen. This 54-year-old man had photosensitivity OU and a history of retinal detachment in his right eye; his visual acuity was 20/200 OU. B, While the sheen is seen as patches in the periphery. These patients exhibit the Mizuo-Nakamura effect on dark adaptation.

Figure 70.2.  

Cone dystrophy with foveal crystals. Right eye of a 58-year-old woman with urban night blindness with nonrecordable photopic ERG and normal scotopic ERGs. Visual acuity was OD 20/40, OS 20/60, and Goldmann visual fields were full.

Figure 70.3.  

Fluorescein angiogram of a 13-year-old girl with a cone dystrophy. The left eye had a large retinal vessel crossing the macula with telangiectatic branches giving some late leakage and edema to the macula. The retinal vessels OD were normal.

A diagnosis of cone degeneration or dysfunction is easily confirmed by a standardized ERG. The International Society for Clinical Electrophysiology and Vision (ISCEV) standardized protocol calls for the cone and rod systems to be tested separately, as well as together in the dark-adapted bright-flash testing. Besides using a single or averaged bright flash under light-adapted conditions, another technique for isolating the cone response is to employ a flickering bright stimulus light with a frequency greater than 20–30 cycles per second (Hz), since the rod response under standard conditions will attenuate fairly severely after 8 Hz and is absent by 20 Hz.⁴ The flicker stimulus, which maximally stimulates the cone system, is useful in bringing out subtle dysfunction or partial cone degenerations, which may not be as apparent by single flash techniques, as the response may be disportionately worse than the single-flash photopic response.²

Cone system dysfunction should be suspected in all patients who complain of photosensitivity, problems in light adaptation, and difficulties with color saturation or discrimination (table 70.1). Patients present with subnormal or abnormal visual acuity that is noncorrectable. A number of patients will have macular atrophy or degenerative changes, some of which start as bull's-eye macular lesions or demonstrated “cookie cutter”—shaped macular atrophy (figure 70.4A and 70.4B). Temporal optic nervehead pallor or atrophy is common in many cone dystrophies (figure 70.5). This change may be mistaken as a “tiled” disk. Abnormal color vision is not an exclusive finding in cone degeneration and may be seen in macular degeneration in macular dystrophies without panretinal cone degeneration. Unless there is a known family history of a cone disorder, an ERG is needed to confirm the diagnosis of cone dystrophy or degeneration, since this diagnosis implies a panretinal cone disorder.

Figure 70.4.  

Fundus photographs of patients with inherited cone dystrophies; A, A 60-year-old man with blue-cone monochromatism who recently noted some mild decreases in his central vision from 20/60 to 20/200, presumably from aging. B, A 54-year-old woman with 20/400 vision OU from a large dominant pedigree with cone dystrophy from a GUCY2D gene mutation, with foveal centralis atrophy giving a “cookie cutter” appearance to macula. This pattern is characteristic of many cone dystrophies.

Figure 70.5.  

Temporal optic nerve head atrophy is commonly seen in many cone degenerations; illustrated here by a 9-year-old boy with rod monochromatism with temporal pallor. Sometimes the temporal edge of the nerve is flattened or missing.

An important fact to remember is the foveal centralis contributes at most only 10–15% to the photopic b-wave amplitude. This fact was confirmed many years ago by examining patients who had foveal scars but otherwise normal retinas. In the face of a macular lesion, a large reduction in the photopic ERG means that there is a cone system dysfunction.¹²

Traditionally, the hereditary cone degenerations and dysfunction disorders have been classified into congenital and later onset forms (table 70.2).^6,8 The two congenital cone dysfunction disorders, blue monocone monochromatism, which is X-linked, and rod monochromatism, which is autosomal-recessive, typically present with congenital nystagmus, and the diagnosis may be missed, or it may be misjudged as congenital nystagmus unless an ERG is performed. The term dystrophy has been broadly used in the ophthalmologic literature, so it is appropriate to use it in congenital-onset cone-loss cases.

Hereditary cone degenerations have been found in all three Mendelian modes of inheritance. A list of the ones currently known are listed in table 70.2. Genetic disease databases, such as RetNet or PubMed, can be used to update this information (see http://www.sph.uth.tmc.edu/retnet or http://www.ncbi.nlm.nih.gov/entrez/query.fcgi).

The electroretinographic pattern in all of these cone-loss disorders is generally the same pattern: The photopic ERG is severely abnormal to nonrecordable by single-flash or computer-averaged methods, while the rod ERG is normal to subnormal (figure 70.6). While the rod tracing might not have a normal amplitude, it is well formed and stable over time in cone dystrophy patients. Dark-adapted tracings frequently show a blink response near the peak of the b-wave, since most patients are photophobic (see figure 70.6). If a scotopic red flash stimulus is employed, the early cone response will be absent, and the later rod response will be present.

Figure 70.6.  

ERG tracings of typical cases of cone dystrophy in which the photopic (cone) signal is nonrecordable to barely discernible (left tracings). In the rod-isolated signal (middle column), the ERG is well formed and is typically normal to subnormal. The bright-flash dark-adapted tracings are subnormal to abnormal in amplitude, and if interpreted alone without the other two tracings, would be misleading and not diagnostic of any condition. The cases illustrated here are a 54-year-old woman with dominant inherited cone dystrophy DOM CD (see figure 70.6B), whose vision was OD 20/200, OS 20/300; a 60-year-old man with X-linked blue cone monochromatism (XL BCM), who came from a large X-linked pedigree–his visual acuity as a young man was 20/60, but by 60 years of age it was 20/200 OU (see figure 70.6A); a 58-year-old man with X-linked cone dystrophy (XL CD) with tapetal-like sheen (see figures 70.3A and 70.3B), who presented with 20/200 vision; and a 20-year-old woman with autosomal-recessive rod monochromatism (AR RM), who presented with 20/200 vision.

Conditions that can be confused initially with cone degeneration are early cases of cone-rod retinitis pigmentosa or cases of RP inversa, in which a cone-rod ERG pattern with dense progressive central scotoma may be found and could otherwise be mistaken for a cone degeneration with mild rod involvement.⁵ Checking the peripheral visual field is an important adjunctive test in all these disorders, and the field is typically stable and full over time. Visual fields, often performed serially, are an important confirmatory test for distinguishing cone disorders from progressive disorders with peripheral loss and may be diagnostic on the initial test. Some cone disorders will have central scotomata whose size is consistent with the level of visual acuity.