RU2444977C2 - Method of diagnosing achromatopsia - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to ophthalmology. Chromatic macular (local) ERG to red stimulus is carried out. Absence of biopotential is registered. Chromatic macular (local) ERG is carried out, amplitude and latency to green stimulus are estimated. Registered are reduction of a-wave amplitude on M-ERG to green stimulus to 28-48%, elongation of a-wave latency to 102-121%, reduction of b-wave amplitude to 66-94%, elongation of b-wave latency to 117-128%. Chromatic macular (local) ERG to blue stimulus is carried out. Registered are reduction of a-wave amplitude to 75-92%, elongation of latency of a-wave to 94-115%, reduction of b-wave amplitude to 80-100%, elongation of b-wave latency to 107-123%. Multifocal ERG ia carried out. Registered are reduction of retinal density P1 to 26-85.5%, reduction of amplitude N1 component to 7-79% and reduction of P1 component to 43-85%, elongation of N1 latency to 132-204% and P1 to 156-186%, mostly in central than in paracentral parts. Mixed ERG is carried out. Registered are reduction of a-wave amplitude to 34-80%, elongation of a-wave latency to 98-117%, b-wave amplitude to 84-105%. High-frequency rhythmic ERG is carried out. Absence or sharply subnormal rhythmic ERG is registered. ERG to long-lasting stimulus is carried out. If there is no OFF-response of ERG to long-lasting stimulus, achromatopsia is diagnosed.

EFFECT: method makes it possible to diagnose achromatopsia by means of electroretinographic methods of examination on the basis of objective electroretinographic criteria and pathognomonic symptomocomplex.

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Description

The invention relates to ophthalmology and is intended for the diagnosis of achromatopsia (synonyms - achromasia, color blindness). Achromatopsia is a rare congenital hereditary disease [the frequency of achromatopsia in a population is 1: 30,000], which is a complete (complete achromatopsia) or almost complete (incomplete achromatopsia) cone system dysfunction. A characteristic feature of achromatopsia is a congenital violation of color perception up to its absence.

State of the art

For the diagnosis of achromatopsia in our country, we used subjective methods of studying color perception - polychromatic tables of the Rabkin type, which are designed to detect abnormal trichromasia and dichromasia, Yustova's table [V.V. Volkov, Yustova], 15- and 100-color panel panels were used and are applied Farnsworth tests. Anomaloscopy is also used to diagnose color anomalies, in particular to identify abnormal trichromasia and dichromasia with a deficiency in the red or green part of the spectrum, as well as a method for assessing the topography of color and contrast sensitivity [Shamshinova A.M. et al., 1997], which is a psychophysical research method, the advantage of which is objectivity. When conducting ECHIL (electrical sensitivity and lability) - a subjective method for assessing the function of the visual apparatus - there is a decrease in thresholds of electrical sensitivity and a decrease in lability.

A known method using a device for diagnosing pathology of the visual system in children, including achromatopsia, at the critical fusion flicker frequency, which is carried out as follows. From a distance of 25-30 cm, a luminous light test is presented with a constantly increasing, and then decreasing flicker frequency. The average value of the threshold frequency of recognition of flicker by a subject with increasing and decreasing frequency is the critical frequency of flicker fusion (Rogatina E.V. et al. "The critical frequency of flicker fusion in the differential diagnosis of pathology of the visual analyzer in children." Herald of Ophthalmology. - 1997. - T.113. - No. 6. - S.20-22). The lower the CFSM, the more severe the lesion of the cone-shaped retinal system. The method is informative, especially in the diagnosis of eye diseases in children, including cone dysfunction, but its disadvantages are its subjectivity and nonspecificity in the diagnosis of this pathology.

The closest analogue of the proposed method is a method for the diagnosis of hereditary diseases of the retina, which includes achromatopsia, by assessing color perception disorders using chromatic macular (local) ERG in the diagnosis of diseases of the macular region of the retina [Shamshinova A.M., Govardovsky V.I., Golubtsov K.V. On the methodology for registering a local ERG // Bulletin of Ophthalmology. - 1989. - No. 6. - S. 47-49]. The method includes recording chromatic macular (local) electroretinography (ERG) for color stimuli and is used to diagnose color anomalies and degenerative diseases of the retina.

However, nonspecificity introduces a significant error in the diagnosis, since a decrease in the amplitude of local ERG by color is noted not only with achromatopsia, but also with other congenital disorders of color perception (abnormal trichromasia and dichromasia) and other degenerative diseases of the macular region of the retina of various etiologies.

Disclosure of invention

Diagnosis of achromatopsia causes great difficulties due to the lack of objective signs pathognomonic for this disease. The main diagnostic errors associated with this category of patients are the diagnosis of progressive macular degeneration. Another most common diagnostic error is a suspicion of partial atrophy of the hepatitis C or inherited or acquired genesis. Diagnostic errors lead to the appointment of unnecessarily expensive examination methods to exclude intracranial pathology, and an inadequate prognosis for a progressive decrease in visual acuity is traumatic for the patient.

At the same time, it is known that electroretinographic signs of achromatopsia are normal scotopic ERG, indicating normal function of the rod system of the retina, and absent (with complete achromatopsia) or sharply subnormal (with blue cone monochromasia) photopic and flickering ERG with a stimulation frequency of 30 Hz, indicating , respectively, about the absence or sharply subnormal function of the cone system. However, these studies are not specific, since they are also characteristic of degenerative diseases of the retina. The form of the biopotential of maximum ERG, which is a combined cone and rod response, corresponds to a scotopic ERG, the time to the peak is elongated.

The objective of the invention is to develop a new approach in the diagnosis of achromatopsia, which allows to diagnose complete and incomplete achromatopsia, a rare form of congenital color vision disorder, manifested by complete color blindness or its incomplete form with residual function of blue cone photoreceptors based on a combination of objective electrophysiological signs in combination with the clinical picture. , further differentiation into full and incomplete achromatopsia is possible based on the type of inheritance - full Achromatopsia is inherited autosomally recessively, incomplete - linked to the X chromosome.

The prerequisites for the development of the proposed method for the diagnosis of achromatopsia were the modern data of neuroanatomy and neurophysiology of the retina (ON bipolar cells were found for all three chromatic types of cones and rods; OFF bipolar cells were found in cone pathways (“red”) cones sensitive to the long-wave (red) part of the spectrum , and (“green”) cones sensitive to the mid-wave (green) part of the spectrum, and are absent in the “blue” cone paths sensitive to the short-wave (blue) part of the spectrum, and rod-shaped paths ). To register ON-OFF responses of the cone system, an ERG for a long stimulus (white flash lasting 200 ms) is used, which allows one to evaluate the total function of ON and OFF bipolar. Using modern methods for assessing the electrogenesis of the macular region of the retina, mainly the cone-shaped system, which includes multifocal ERG of the retina, OFF-bipolar cells make a significant contribution to the N1 component of the biopotential, and ON-bipolar cells to the P1 component, which allows predicting specific changes. Generalized cone dysfunction suggests the presence of a similar nature of changes in all topographic zones, to a greater extent in areas of complete absence of cone function. The absence of macular ERG on the red stimulus during achromatopsia indicates the absence of the function of the red cone-shaped system, as noted earlier.

The technical result of the invention is the objectification of the diagnosis of achromatopsia with the development of a pathognomonic complex of electroretinographic signs.

The technical result is achieved through the use of a complex of electroretinographic research methods with registration of the bioelectrical activity of the retina in accordance with the protocol of ERG registration methods, which are included in ISCEV standards, in particular mixed ERG and rhythmic ERG at 30 Hz (registration was performed on an MBR electroretinograph, Russia), registration of a local ERG to a chromatic stimulus (red, green, and blue) with a suction electrode, registration of an ERG to a long stimulus (stimulus duration - 200 ms), multifocal ERG (mf-ERG).

Thus, a combination of the characteristic biopotentials obtained using various electroretinographic research methods can accurately diagnose achromatopsia and distinguishes the method from other analogues.

The implementation of the invention

The method is as follows.

The method is illustrated in figures 1-5, where figure 1 is a photograph of the fundus with achromatopsia (a - the right eye, b - the left eye); figure 2 - mixed ERG (a - the right eye, b - the left eye) and macular chromatic (local) ERG on the red stimulus (c - the right eye, d - the left eye) and the green stimulus (d - the right eye, e - the left eyes); figure 3 - rhythmic ERG at 30 Hz (a - right eye, b - left eye); figure 4 - ERG for a long stimulus (a - right eye, b - left eye); figure 5. - A typical form of the bioelectric response of a multifocal ERG (mf-ERG) in achromatopsia.

Register mixed ERG on a white stimulus in the conditions of dark adaptation with a 3-minute dark pre-adaptation. When evaluating the result, a gentle form of the biopotential is noted, which is similar to scotopic ERG when the amplitude of the a-wave is reduced to 34-80% from the lower limit of the norm, the latency of the a-wave is extended to 98-117% from the upper limit of the norm, the b-wave is reduced or normal limits, accounting for 84-105% of the lower limit, and b-waves to 76-110% of the upper.

An ERG is recorded for a rhythmic white stimulus (stimulation frequency 30 Hz) - a lack of response or a sharply subnormal biopotential is noted.

Record an ERG for a long stimulus (stimulus duration 200 ms) - note the absence of an OFF response.

Chromatic macular (local) ERG is recorded on the red stimulus using a suction cup electrode. Note the lack of biopotential macular ERG.

Chromatic macular (local) ERG is recorded on the green stimulus. A gentle form of the biopotential is noted: a decrease in the amplitude of the a-wave on the M-ERG by the green stimulus to 28-48% from the lower limit of the norm, lengthening the latency of the a-wave to 102-121%, reducing the b-wave to 66-94%, lengthening the latency b-waves up to 117-128%.

Chromatic macular (local) ERG is recorded on the blue stimulus. There is a decrease in the amplitude of the a-wave to 75-92% of the lower limit of the norm, an extension of the latency of the a-wave from 94% to 115% of the upper limit of the norm, a decrease in the amplitude of the b-wave from 80 to 100% from the lower limit, lengthening of the latency b- waves up to 107-123% of the top.

Multifocal electroretinography is recorded (in daylight) on a grid of 37 hexagons (more preferably than 61 hexagons). A bioelectric response is estimated, averaged over rings with different distances from the center. With a decrease in the retinal density of P1 from 26-85.5%, the amplitudes of N1% of the component from 7 to 79% and P1 of the component to 43-85% and more than normal, lengthening the latency of N1 to 132-204% and P1 to 156-186% more in the central than in the paracentral sections.

Incomplete achromatopsia is characterized by dysfunction of long-wave-sensitive and medium-wave-sensitive cones, which is manifested by a decrease in visual acuity, a gross violation of color perception in the red and green parts of the spectrum, determined by polychromatic tables, a decrease in visual acuity, and lack of proper differentiation of fovea (smoothness of foveal). The absence of chromatic macular ERG to the red stimulus in combination with the absence of the OFF response of the cone system indicates the absence of function of the red cone system. The lack of an OFF response is an indirect sign of the lack of function of the green cone system, as indicated by a decrease in M-ERG to green. The cone-shaped system is involved in the response to the green stimulus. In the ERG for a long stimulus, the OFF response is not recorded, which is a reliable sign of complete dysfunction of the OFF channels of the red and green cones. This form of mf-ERG biopotential is specific and was found by us from more than 500 examined patients only with achromatopsia. The specific form of the response (a decrease in the amplitude of N1 and a prolongation of time to the peak of P1) is explained by the lack of OFF-bipolar function, i.e., the source of the negative component N1 is exclusively photoreceptors (rods and, with incomplete achromatopsia, blue cones), and the main source of component P1 are ON-bipolar blue cones.

Clinical examples

Patient K., 7 years old, with complaints of decreased visual acuity from birth, photophobia, impaired color perception. Visual acuity OD sph + 1.25 = 0.2 n / a OS sph + 0.75 cyl + 0.75 ax 20 = 0.2 n / a. A study of color perception was carried out according to Rabkin's color tables, the results of which indicated a gross violation of color vision and made it possible to suspect achromatopsia. Photograph of the fundus with a characteristic ophthalmoscopic picture is presented in figure 1.

Registered mixed (maximum) ERG. A gentle form of the biopotential was noted, which is similar to scotopic ERG, lengthening of the a-wave latency to 32 ms and lengthening of the b-wave latency to 83 ms (Fig. 2, a, b).

Chromatic macular (local) ERG was recorded on the red stimulus using a suction electrode. Noted the lack of biopotential macular ERG (Fig.2, c, d).

Registered local chromatic ERG to the green stimulus. A gentle form of the biopotential was noted: a-wave amplitude decreased to 1.4 μV in the right eye and 1.0 μV in the left eye; lengthening the time to the peak (latency) of the a-wave to 33 ms of the right and left eye, reducing the amplitude of the b-wave to 18.2 μV of the right eye and 17.6 μV of the left eye, lengthening the time to the peak (latency) of the b-wave to 83 ms of the right and left eye (Fig.2, d, e).

The local chromatic ERG to the blue stimulus was recorded. The amplitude of the a-wave was 4.5 μV in the right eye and 5.06 μV in the left; the latency of the a-wave is 33 ms of the right and left eye, the amplitude of the b-wave is 60 μV of the right eye and 52 μV of the left eye, lengthening the time to the peak (latency) of the b-wave to 83 ms of the right and left eye.

Rhythmic ERG at 30 Hz was recorded, a sharply subnormal potential was noted, a decrease in amplitude to 2 μV in both eyes (Fig. 3).

ERG was recorded for a long stimulus of 200 ms. The absence of an OFF response was noted (FIG. 4).

Mf-ERG was recorded on a grid of 37 hexagons. A decrease in retinal density from 3.4 to 21.9 nV / deg ² , a decrease in the amplitude of the N1 component from 0.02 to 0.36 μV and P1 of the ERG components from 0.32 to 0.88 μV, an extension of the latency of the N1 component from 25 were noted , 5 to 34 ms and the extension of the latency of the P1 component to 56-58 ms, depending on the analysis zone. The data are presented in the table in illustrative material (figure 5).

Based on the data obtained, the diagnosis of achromatopsia was made. The patient is observed in dynamics for 5 years. Repeated studies revealed indicators that did not decrease over time. Since there is no negative dynamics with this pathology, this confirms the diagnosis of achromatopsia.

Thus, a combination of five electroretinographic techniques (mixed ERG, local ERG for the red and green stimulus, rhythmic ERG, long-term stimulus and mf-ERG) against the background of known changes in the ophthalmoscopic picture, decreased visual acuity and color perception allow the diagnosis of achromatopsia. The combination of these signs is specific for achromatopsia and allows you to effectively diagnose the disease.

Claims (1)

A method for diagnosing achromatopsia, including performing chromatic macular (local) ERG, characterized in that the chromatic macular (local) ERG for green and blue stimuli, multifocal mixed ERG, rhythmic ERG, ERG for a long-term stimulus and in the absence of the biopotential of chromatic macular (local) are also recorded ) ERG to the red stimulus during registration of chromatic macular (local) ERG additionally evaluate the amplitude and latency of the green and blue stimuli in the macular region and with a decrease in a-wave plateau on M-ERG on a green stimulus up to 28-48%, a-wave latency lengthening to 102-121%, a b-wave amplitude decrease to 66-94%, a b-wave latency lengthening to 117-128% and by reducing the amplitude of the a-wave to 75-92%, lengthening the latency of the a-wave to 94-115%, reducing the amplitude of the b-wave to 80-100%, extending the latency of the b-wave to 107-123% M-ERG to the blue stimulus with a decrease in the retinal density P1 to 26-85.5% of the amplitude of the N1 component to 7-79% and the P1 component to 43-85%, lengthening the latency of N1 to 132-204% and P1 to 156-186% to a greater extent in the central than in the paracentral sections with regis mf-ERG traction, with decreasing a-wave amplitude to 34-80%, lengthening a-wave latency to 98-117%, a-wave amplitude to 84-105% and b-wave amplitude to 76-110% when mixed ERG, in the absence or sharply subnormal amplitude of the rhythmic ERG; in the absence of an OFF-response of the ERG to a long-term stimulus, achromatopsia is diagnosed.

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