RU2765015C1 - Method for multimodal differential diagnosis of chronic central serous chorioretinopathy and vitelliform dystrophies in adult patients - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular ophthalmology. The time of the appearance of the first complaints, the presence of massive subretinal deposits according to the data of structural optical coherence tomography of the retina, the presence of additional hypo-autofluorescent or hyperautofluorescent points or areas outside the main focus, and the presence of hyperautofluorescence in the form of "beads" according to the data of short-wave autofluorescence are determined. Then the probability of the patient having central serous chorioretinopathy and vitelliform dystrophies is calculated using the formula. With B from 0.5 to 1.0, a conclusion is made about the probable presence of vitelliform dystrophies in the patient, and with B from 0.0 to 0.49, about the probable presence of chronic central serous chorioretinopathy.

EFFECT: method allows to optimize the differential diagnosis of chronic central serous chorioretinopathy and vitelliform dystrophies in adult patients.

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Description

The invention relates to the field of medicine, in particular ophthalmology, and in particular to a method for the differential diagnosis of chronic central serous chorioretinopathy and vitelliform dystrophies in adult patients.

In clinical practice, in some cases there are difficulties in the differential diagnosis of CSH and VD. Vitelliform dystrophy occurring in adults is a heterogeneous group of degenerative diseases with deposition of subretinal vitelliform material [1]. More often these are patients with Best's vitelliform dystrophy and autosomal recessive bestrophinopathy with a late onset of the disease or previously undiagnosed in pediatric practice, as well as patients with common variants of pattern dystrophy: adult vitelliform dystrophy and pattern dystrophy in the form of "butterfly wings". Best's vitelliform dystrophy and autosomal recessive bestrophinopathy are caused by mutations in the BEST1 gene, they are characterized by a decrease in the Arden coefficient during an electrophysiological study. In patients with pattern dystrophies, in some cases, mutations in the BEST1, PRPH2, IMPG1, IMPG2 genes are detected, however, in the vast majority of them, normal parameters are found in electrooculography, the absence of mutations in the above genes [2, 3, 4, 5], the absence of a positive family history, which limits the use of genetic tests and electrophysiological studies in the structure of the differential diagnosis of VD occurring in adulthood with chronic CSR.

CSH - ranks fourth among retinopathy after AMD, diabetic retinopathy, retinal vein occlusion [6]. In about a third of cases, if neuroepithelial detachment (ONE) persists for more than six months, the disease becomes chronic [7]. Along with changes in the retinal pigment epithelium (RPE), CSC is characterized by subretinal deposits, a sign of a “double layer” [7], which makes it difficult to differentiate from age-related macular degeneration (AMD), VD, and a number of other diseases.

The most difficult in differential diagnosis are cases in which clinical manifestations include a combination of long-term ONE with partial or complete resorption of vitelliform material in VD or with deposition of subretinal deposits at the RPE level in chronic CSC (Fig. 1).

In FIG. Figure 1 presents the results of OCT in patients with adult VD and chronic CSC. All scans show detachment of NE, deposition of optically dense deposits along the posterior surface of the ONE, elongation of photoreceptors, a, c - OCT of adult patients with VD (a - without deposition of subretinal material along the RPE, c - with deposition of subretinal material along the RPE). b, d - OCT of patients with chronic CSC (b - without deposition of subretinal material along the RPE, d - with deposition of subretinal material along the RPE).

Differential diagnosis of these diseases requires a large number of labor-intensive, expensive studies, some of which are invasive. Young Seob Lee et al. proposed to consider clinical cases with long-term bilateral serous ONE, rigid to photodynamic therapy (PDT) and intravitreal angiogenesis inhibitors (IVVIA), as variants of the course of vitelliform dystrophies [8]. Luca Zatreanu et al. recommended considering the diagnosis of VD in patients with ONE and persistent subretinal fluid masquerading as neovascular AMD or chronic CSC to avoid unnecessary medical procedures [9].

Improving the differential diagnosis of chronic CSC and VD in adults based on the study of data from multimodal studies and the development of optimal non-invasive algorithms for their implementation are very urgent tasks. An accurate diagnosis reduces the risks of inappropriate treatment of patients with VD with therapies used for CSC, such as PDT [10], micropulse and conventional laser coagulation [11], and for AMD, such as IVVIA.

There is a method for the differential diagnosis of central hereditary retinal dystrophies (CRI) [12], during which anamnestic data are revealed: the presence of CRI in relatives, the age at which the first complaints of reduced visual acuity appeared in the subject; clinical data: visual acuity, type of focus in the macular area; changing 3D-CTAG parameters. Based on the data obtained, the disease of the CND is diagnosed. In the presence of relatives with Stargardt's CNDS, the appearance of: the first complaints of decreased visual acuity in a subject aged 10-20 years; clinical data: there is no foveolar reflex in the macular region, atrophic foci such as "broken metal", "bull's eye", "forged bronze" or atrophy of the choroid appear; 3D-CTAG data: the presence of one central defect that extends to all levels of contrast, having a different area at different contrast levels, the total lost area is less than 100%, diagnose Stargardt's central retinal dystrophy. In the presence of relatives with Best's dystrophy, the appearance of the first complaints of decreased visual acuity in a subject aged 5-15 years; clinical data: in the macula, a rounded, clearly delimited formation resembling an egg yolk; 3D-CTAG data: the presence of one central defect that extends to all contrast levels, has almost the same area at different contrast levels, occupies 1.0-2.0% of the hill of vision, zero contrast level 4-10%, the total lost area is about 100%o, Best's vitelliform dystrophy was diagnosed. In the presence of relatives with retinitis pigmentosa, the appearance of the first complaints of a decrease in visual acuity in a subject under the age of 30: clinical data: in the macular region, typical pigmented lesions are “bone bodies”; 3D-CTAG data: the presence of one central defect that extends to all levels of contrast, having a different area at different contrast levels, the total lost area is less than 100%, diagnose the central form of retinitis pigmentosa.

The above method does not affect cases of vitelliform dystrophies, when they are difficult to distinguish from central serous chorioretinopathy, which occurs in the later stages of the disease. This division is of practical importance, since cases of central serous chorioretinopathy require active flow methods, such as PDT, micropulse therapy, and leak point laser coagulation.

None of the known methods is suitable for the differential diagnosis of chronic central serous chorioretinopathy and vitelliform dystrophies, therefore, none of the known solutions was taken as a prototype.

The technical problem lies in the need to develop a simple and effective method for the differential diagnosis of chronic central serous chorioretinopathy and vitelliform dystrophies in adult patients at later stages of the process.

The technical result consists in optimizing the differential diagnosis of chronic central serous chorioretinopathy and vitelliform dystrophies in adult patients.

The technical result is achieved by the fact that in the method of differential diagnosis of chronic central serous chorioretinopathy and vitelliform dystrophies in adult patients, the time of appearance of the first complaints, the presence of massive subretinal deposits, as well as the criteria for short-wave autofluorescence are determined: the presence of additional hypoautofluorescent or hyperautofluorescent points or areas outside the main focus and the presence hyperautofluorescence in the form of "beads", and then calculate the probability of a patient having central serous chorioretinopathy and vitelliform dystrophies using the following formula:

где

where

MD - the presence of massive subretinal deposits, denoted - 1 in the presence of MD, 0 - in the absence,

HPV - the time of the appearance of the first complaints, determines the duration of the period during which the patient notes the presence of visual complaints: from six months to a year - 0, with a duration of two to five years - 1, with a duration of more than five years - 2,

DAF - additional hypoautofluorescent or hyperautofluorescent points or areas outside the main focus, where, if present, DAF is equal to 1, and in the absence - 0,

APB - the presence of hyperautofluorescence in the form of "beads", where in their presence APB is 1, and in the absence - 0,

at B from 0.5 to 1.0, a conclusion is made about the probable presence of vitelliform dystrophies in the patient, and at B from 0.0 to 0.49 - about the probable presence of chronic central serous chorioretinopathy.

The proposed method provides optimization of the differential diagnosis of chronic central serous chorioretinopathy and vitelliform dystrophies in adult patients. This method allows you to simplify the differential diagnosis and carry it out using non-invasive research methods.

The choice of optimal diagnostic criteria and calculation formulas was made as follows.

The study included 61 patients (90 eyes) with a clinical picture requiring differential diagnosis between adult VD and CSC. The inclusion criteria were: persistence of complaints of reduced visual acuity for more than six months, the presence of a yellowish focus in the macular zone, determined during biomicroophthalmoscopy, the presence of ONE and subretinal hyperreflective material (deposits) detected during structural OCT.

In all patients, an anamnesis was collected, including family history, standard ophthalmological examination methods and multimodal diagnostics were performed. When collecting a family history, special attention was paid to the presence of complaints of decreased vision in blood relatives (children, parents, siblings). In these cases, relatives were examined for the presence of similar changes in the fundus. When collecting an anamnesis of the disease, the time of appearance of the first visual complaints was noted: from six months to 2 years, from 2 years to 5 years, from 5 years and more.

Standard methods included visometry using an automatic sign projector to determine BCVA, biomicroophthalmoscopy using 60D and 90D aspherical lenses. During biomicroophthalmoscopy, the involvement of the contralateral eye was assessed: the presence of ONE, pigment epitheliopathy, cicatricial, atrophic changes were determined. All paired eyes were examined according to the same algorithm as the eyes included in the main statistical processing.

Multimodal diagnostics included photoregistration of the fundus using a fundus camera "Visucam", Carl Zeiss Meditec (Germany); OCT of the macular area (structural and OCT-A) on the RTVue XR Avanti device, Optovue, USA; CV-AF of the macular area, FAG, ISAH on the device "Heidelberg SPECTRALIS HRA + OCT2 MultiColor", Heidelberg Engineering. All studies of the fundus were performed under conditions of drug-induced mydriasis. OCT was performed according to the Cross Line protocol when the scans passed through the center of the fovea, OCT-A was performed according to the HD Angio Retina 3.00×3.00 and 6.00×6.00 Scan Size protocols in En-Face mode using the capabilities of the AngioVue software.

After a complex of studies, patients were divided into 2 groups: 30 people (57 eyes) with VD adults and 31 people (33 eyes) with chronic CSC. Along with the long-term ONE and the deposition of subretinal hyperreflective material (deposits), the criteria for making a diagnosis from the group of multimodal studies were determined. The pathognomonic criteria for diagnosing VD in adults were considered the presence of a luminescence block according to the AIH data and in the early phase of the FAH in the area of the subretinal material with a gradual accumulation of the dye in the same area according to the FAG in the late phases of the study. The criteria for the diagnosis of chronic CSC were the presence of active leak points or zones of leakage from an undetectable source according to FAG in combination with a change in RPE, expansion, hyperpermeability of the choroidal vessels according to ISAH.

Based on our previous study, we studied the diagnostic signs obtained by standard and multimodal research methods, which occur both in CSC and in VD. Of the identified 80 criteria, a pool of 52 most informative ones was identified: age, BCVA, involvement of the contralateral eye, time of first complaints, positive family history, as well as criteria for multimodal studies presented in Table 1.

Table 1. Criteria for multimodal diagnosis. ^* When determining the brightness, the Grayscale scale [14] was used. In the Grayscale model for 8-bit images, a black-and-white image pixel is characterized by a brightness value ranging from 0 (black) to 255 (white). The brightness on this scale was determined in degrees from 1 to 4, where 4 is the brightest.

Statistical processing included 61 patients (61 eyes): 30 with VD adults and 31 with chronic CSC. Statistical analysis was carried out using the SAS v9.4 software. The results were considered statistically significant at p<0.05.

Binary logistic regression was used to assess the probability of detecting a disease based on the predictors obtained during the preliminary studies. To this end, a stepwise regression analysis was carried out. The predictive evaluation of the logistic regression model was performed using ROC analysis, the optimal cutoff point was determined, and the sensitivity and specificity for the resulting model were calculated. The quality of model recognition was assessed by the area under the characteristic curve; when assessing the quality of the model, the classification of N.V. Trukhacheva was used. (2013) [13].

Based on the diagnostic criteria assessment data, 16 significant models of the probability of detecting VD in adults were built using various combinations of diagnostic research methods, including an expert model using the criteria of a complete multimodal diagnosis.

Figure 2 shows an example of a multimodal diagnosis of an adult VD patient:

a - photo of the retina (in the macula, a light area less than 1 optic disc in diameter, the zone of pigment redistribution);

b - fundus CV-AF (area of hyperAF surrounded by a hypoAF ring with a confluent more intense hyperAF area below them, hyperAF brightness - 3 on the Grayscale scale);

f - structural OCT (ONE, hyperreflective partially resorbed vitelliform material, elongated, partially resorbed photoreceptors, subretinal deposits in the form of separate short "stalactites", diffusely dilated choroidal vessels and thickening of the wall of Haller's vessels);

ƒ - OCT-A (shadow from the ONE with subretinal material, rarefaction of the choriocapillary layer along the edge of the ONE in areas of RPE atrophy);

g - IZAG (luminescence block in the zone of deposition of vitelliform material, choroidal vessels are not dilated);

c, d - FAH arteriovenous phase and dye recirculation phase, respectively (block of luminescence by vitelliform material with subsequent accumulation of dye in this zone).

The figure 3 shows an example of a multimodal diagnosis of a patient with chronic CSC:

a - photo of the retina (in the macula, a light area about 1 pd in size);

b - fundus CV-AF (background hypoAF, central confluent hyperAF, diffuse hyperAF along the lower edge of the focus, hyperAF brightness - 2 on the Grayscale scale);

f - structural OCT (ONE, hyperreflective deposits along the RPE, elongation of photoreceptors, deposits in the form of a "dense fringe", diffusion dilated choroidal vessels):

ƒ - OKT-A (penumbra from ONE with subretinal material);

c - FAG (dye accumulation in the temporal parafoveolar zone from an undetectable source);

d - IAH middle phase (dilation of the choriridal veins, choroidal hyperpermeability).

From the obtained models for assessing the probability of detecting a disease, the best one with the largest area under the characteristic curve, as well as with the optimal set of non-invasive diagnostic tests, was selected.

To calculate the probability of detecting VDs, the formula obtained in the regression analysis for each model was used. The result of calculations according to the formula from 0.5 to 1.0 indicates the probable presence of adult VD in the patient, from 0.0 to 0.5 - the probable presence of chronic CSC. The results of the sensitivity, specificity, and accuracy of the model are presented in Table 2. The quality of model recognition was assessed by the area under the characteristic curve; at values from 0.9 to 1.0, the quality of the model is defined as “excellent” [13].

Adult VD and chronic CSC share many common features. So both diseases are characterized by diffuse or local expansion of the vessels of the Haller layer with thinning of the choriocapillaries in their projection. In both conditions, subretinal deposits are observed, indicating a pathological process in the RPE area, the outer segments of photoreceptors. With a long course of VD in adults and CSC, hyperreflective points are visualized in the neuroepithelium and choroid, subretinal space, thickening of the walls of choroidal vessels, and degenerative cystic changes in the neuroepithelium. Such a commonality may indicate the presence of common links in the pathogenesis of these diseases. However, the use of identical methods of treatment for these diseases is not justified and even dangerous. For example, PDT, which is the method of choice for chronic CSC uncomplicated by CNV, in the treatment of patients with VD, at best, does not lead to the desired result, and at worst, can cause a significant decrease in visual acuity [15, 16]. This suggests that the search for the optimal differential diagnosis of AD in adults and chronic CSR is very relevant.

Our study showed that for the correct delivery of the diagnosis, it is not necessary to conduct an expensive, time-consuming and invasive multimodal diagnosis.

The model included criteria for structural OCT, OCT-A, CV-AF, which significantly improved its quality (sensitivity 93.3%, area under the curve 0.980), while OCT-A criteria were not included in the formula for the probability of detecting a disease as less significant, simplifying multimodal diagnosis to structural OCT and CV-AF.

Based on the sensitivity, specificity, and area under the characteristic curve data, it can be concluded that the obtained model is adequate and can be used to assess the probability of detecting diseases with high accuracy. For the resulting model, the area under the characteristic curve is greater than 0.9, which indicates its "excellent" quality. The proposed algorithm for the multimodal differential diagnosis of VA in adults and chronic CSR makes it possible to make a diagnosis in a simpler and more cost-effective way, taking into account the use of various combinations of methods in conditions of different equipment of clinics.

The model will be available if the clinic has a high-resolution optical coherence tomograph and a fundus camera for CV-AF.

The inventive method is carried out as follows.

During the survey, the time of the appearance of the first complaints is determined. Then, according to structural optical coherence tomography, the presence of massive subretinal deposits is determined, according to short-wave autofluorescence, the presence of additional hypoautofluorescent or hyperautofluorescent points or areas outside the main focus and the presence of hyperautofluorescence in the form of "beads" are determined. Then the diagnosis is determined by the formula:

где

where

MD - the presence of massive subretinal deposits, denoted - 1 in the presence of MD, 0 - in the absence,

HPV - the time of the appearance of the first complaints, determines the duration of the period during which the patient notes the presence of visual complaints: from six months to a year - 0, with a duration of two to five years - 1, with a duration of more than five years - 2,

DAF - additional hypoautofluorescent or hyperautofluorescent points or areas outside the main focus, where, if present, DAF is equal to 1, and in the absence - 0,

APB - the presence of hyperautofluorescence in the form of "beads", where in their presence APB is 1, and in the absence - 0,

at B from 0.5 to 1.0, a conclusion is made about the probable presence of vitelliform dystrophies in the patient, and at B from 0.0 to 0.49 - about the probable presence of chronic central serous chorioretinopathy.

The claimed method is illustrated by examples.

Example 1

A 67-year-old patient has a clinical picture corresponding to chronic central serous chorioretinopathy or vitelliform dystrophy. For differential diagnosis was used the first version of the proposed method. The diagnosis was determined by the formula:

Since B is equal to 0.584, it was concluded that the patient may have vitelliform dystrophies. Additional diagnostic measures confirmed the presence of vitelliform dystrophies in the patient.

The diagnosis was confirmed by the data of invasive studies: fluorescein angiography of the retina (FAG) and idocyanine-green angiography of the retina (IDAG).

All patients had a long-term detachment of the neuroepithelium, subretinal material in the form of deposits or deposits. The criteria for diagnosing VD in adults were the presence of a block of luminescence according to the AIH and in the early phase of the FAH in the zone of subretinal material with a gradual accumulation of the dye in the same zone according to the FAG in the late phases of the study. The criteria for the diagnosis of chronic CSC were considered to be the presence of active leak points or zones of leakage from an undetectable source according to FAG in combination with a change in the retinal pigment epithelium, expansion, hyperpermeability of the choroidal vessels according to ISAG.

Example 2

A 51-year-old patient has a clinical picture corresponding to chronic central serous chorioretinopathy or vitelliform dystrophy. For differential diagnosis was used the first version of the proposed method. The diagnosis was determined by the formula:

Since B is equal to 0.216, it was concluded that the patient probably has chronic central serous chorioretinopathy. Additional diagnostic measures confirmed the presence of chronic central serous chorioretinopathy in the patient.

Confirmation of the diagnosis was carried out according to example 1.

List of sources

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Claims (7)

A method for the differential diagnosis of chronic central serous chorioretinopathy and vitelliform dystrophies in adult patients, during which the time of appearance of the first complaints, the presence of massive subretinal deposits according to structural optical coherence tomography of the retina, the presence of additional hypoautofluorescent or hyperautofluorescent points or areas outside the main focus and the presence of hyperautofluorescence in in the form of "beads" according to the data of short-wave autofluorescence, and then calculate the probability of a patient having central serous chorioretinopathy and vitelliform dystrophies according to the following formula:

where MD - the presence of massive subretinal deposits, denoted - 1 in the presence of MD, 0 - in the absence, HPV - the time of the appearance of the first complaints, determines the duration of the period during which the patient notes the presence of visual complaints: from six months to a year - 0, with a duration of two to five years - 1, with a duration of more than five years - 2, DAF - additional hypoautofluorescent or hyperautofluorescent points or areas outside the main focus, where, if present, DAF is equal to 1, and in the absence - 0, APB - the presence of hyperautofluorescence in the form of "beads", where in their presence APB is equal to 1, and in the absence - 0, at B from 0.5 to 1.0, a conclusion is made about the probable presence of vitelliform dystrophies in the patient, and at B from 0.0 to 0.49 - about the probable presence of chronic central serous chorioretinopathy.

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