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Bakhritdinova Fazilat Arifovna, MD, professor of Department of Ophthalmology.
Tashkent Medical Academy E-mail: [email protected] Kangilbaeva Guzal Erkinovna, assistant of Department of Ophthalmology Tashkent Medical Academy E-mail: [email protected] Mirrakhimova Saida Shukhratovna, Head of Samarkand Rejional Eye Hospital MD, associate professor of Ophthalmological Department.
Samarkand Medical Institute Jurabekova Aziza Zakirovna, Master of Ophthalmology Tashkent Medical Academy, Uzbekistan E-mail: [email protected]
DEVELOPMENT OF DOPPLEROGRAPHIC CRITERIA FOR THE PROGRESSION AND PROGNOSIS OF DIABETIC RETINOPATHY
Abstract: The authors studied the correlation between the volumetric rate of blood flow and the severity of retinopathy, and developed a risk index for the progression of diabetic retinopathy. A pathogenetically grounded method of treatment with nonproliferative diabetic retinopathy is proposed, the effectiveness of which is confirmed by the risk index of progression.
Keywords: retinopathy, maximal systolic blood flow velocity, index of severity of retinopathy.
In connection with the wide and prevalence of dia- is synthesized from L-arginine with the participation of betes mellitus (DM) according to WHO preliminary NO-synthases, increased production of NO in retinal data, more than 360 million people will be affected by ischemia leads to depletion of the source of NO synthesis
diabetes by 2030. Along with other vascular complica- -L-arginine [1] and, accordingly, to a decrease in NO syn-
tions of diabetes, diabetic retinopathy (DR) is a serious thesis. There is a weakening of NO-dependent processes,
problem, leading to blindness and disability. In connection such as vasodilation, platelet aggregation increases. This
with this, further study of the pathogenetic mechanisms leads to the further development of micro-thrombosis
underlying the development of DR and the search for the of the vascular system and local ischemia of the retina,
best, pathogenetically conditioned treatment of nonpro- which in turn stimulates the synthesis of vaso- prolifera-
liferative diabetic retinopathy (NDR) are topical. tive factors and, as a consequence, neovascularization
With prolonged glycemia, the capillary walls change and proliferation [2, 3]. According to the literature data
(thickening of the basement membrane, the disappear- [7, 10], in the early stages of the development of diabetic
ance of pericytes, changes in endothelial cells) and the retinopathy, increased NO production leads to an increase
rheological properties of the circulating blood, which in the volume blood flow in the retinal and orbital arteries,
contributes to the formation of microthrombi and the which is a compensatory mechanism for ensuring normal
occlusion of capillaries. Local hypoxia of tissues arises, blood supply and maintaining a high level of metabolism
which in turn leads to an increase in the synthesis of nitric in tissues lacking oxygen or nutrients. According to the
oxide (NO), a powerful vasodilator. It is known that NO data of other authors [2, 9], from the very beginning of
development of DR, there is a progressive decrease in the volume blood flow in the vessels of the retina and orbital artery. The inconsistency of the literature data on the blood flow in the eye vessels at different stages of the DR and the significance of hemodynamic changes in the pathogenesis of DR cause the need for further study and development of ultrasonic diagnostic and prognosis criteria for DR. Correlative connections of changes in the hemodynamics of the eye with the severity of retinopathy remain unexplained. The solution of the problem of effective therapy of NDR is impossible without taking into account the pathogenetic mechanisms of the disease and should pursue the goal of a balanced and targeted influence on the general links of the process. In this regard, the study of the interaction of key pathophysiological factors that affect the nature of angiogenic changes in the retina is of great scientific and practical interest.
Purpose: To study the Dopplerographic criteria for the progression of NDR and evaluate the effectiveness of treatment with the inclusion ofendonasal electrophoresis with tanakan based on the index of progression of NDR.
Materials and methods. Clinical studies were conducted during the treatment of 108 patients (197 eyes).
Of these, 76 eyes with NDR Ia stage, 75 eyes with NDR Ib and 46 eyes with NDR Ic stages. The age of patients was in the range of 18-81 years, men — 43, women — 65. Depending on the performing conservative treatment, all patients were divided into 3 groups:
1 (control) group — 36 patients (65 eyes). Standard treatment was received (systemic: hypoglycemic preparations, angioprotectors, metabolic treatment, nootropil i/v and local with the use of emoxipin p / b).
2 (I main) group — 36 patients (63 eyes). On the background of standard treatment in 1 group, received instead of nootropil — tanakan in tablets.
3 (II main) group — 36 patients (69 eyes). On the background of treatment of patients in the second group, instead of emoxipin, tanakan was obtained in the form of endonasal electrophoresis. Groups are homogeneous by sex, age and stages of NDR.
The stages were determined by ETDRS classification, widely used in scientific studies and publications, based on the modified scheme of Airlie House [4]. A group of 10 healthy people aged 50 to 60 years old was also under observation. Before the treatment and after the course of therapy, the patients underwent a general ophthalmologi-cal examination and color duplex mapping of the vessels of the eye.
Results and discussion. When assessing the blood flow in the vessels of the eyeball and the retrobulbar space before treatment, increased blood flow was observed in the CRA in the initial stage of the NDR stage and a progressive truth (p <0.001) decrease in blood flow in the CRA and PSCA in the second Ib and third Ic stage of the NDR compared with normal values, as well as an unreliable increase in the resistance index (RI) of the CRA and PSCA (Table 1).
Table 1.- Hemodynamic data for the stages before treatment (M ± m)
CRAV PSCA RI PSCA V PSCA RI OА V OА RI
Practically healthy 13.7 ± 0.3 0.68 ± 0.009 PSCA V 0.667 ± 0.01 41.7 ± 0.7 0,764 ± 0,01
NDR Ia 14.7 ± 1.12 0.72 ± 0.002 OA V 0.65 ± 0.008 30.2 ± 3.3 0,72 ± 0,02
NDR Ib 7.3 ± 0.27** 0.73 ± 0.007 10.6 ± 0.4** 0.71 ± 0.005* 44.4 ± 2.2 0,73 ± 0,02
NDR Ic 5.03 ± 0.33** 0.65 ± 0.01 9.8 ± 0.6** 0.70 ± 0.01 34.7 ± 2.26 0,77 ± 0,02
Note. Vs is the maximum systolic blood flow velocity; * p indicators before treatment
The dynamics of ophthalmoscopic changes in the retina in the pre- and posttreatment period was assessed using a scoring scale developed by us on the basis of the classification of the American Academy of Ophthalmology (2003), which is based on the final severity scale of ETDRS [4, 6] and corresponds to the problems of early detection of DR in patients SD. The index of
< 0.05; ** p < 0.01 - reliability of differences with respect to
severity of retinopathy was assessed by a 20-point system (Table 2). A mean inverse in Ia and a strong inverse in the Ib - Ic stages of the correlation between the space velocity of blood flow in the CS, OCCA and the severity of retinopathy were detected. In connection with which these hemodynamic indicators can be the criteria for diagnosing the stages of PDR (Table 1).
Table 2.- Correlation of the volumetric flow velocity with the gravity index of severity the DR
Stages of DR The index of severity of retinopathy The correlation coefficient of the maximum blood flow velocity with the severity of retinopathy (r)
CRA V PSCA V OA V
NDR Ia 5.5 ± 0.2 -0.53 -0.55 0.25
NDR Ib 8.6 ± 0.25 -0.68 -0.75 -0.33
NDR Ic 15.2 ± 0.4 -0.75 -0.81 -0.13
A mean inverse in Ia and a strong inverse in the Ib - Ic stages ofthe correlation between the velocity ofblood flow in the CRA, PSCA and the severity of retinopathy were detected. In connection with which these hemodynamic indicators can be the criteria for diagnosing the stages of NDR (Table 1). A month after the therapy, the ophthalmoscopic picture improved in all groups, the severity in-
dex of DR significantly decreased in the second and third groups. Long-term follow-up showed that progression of diabetic retinopathy was observed at 51 eyes (78%) at 6 months in the control group, and in 12 eyes (18.5%) NDR progressed to the proliferative stage, whereas in the main groups the result of treatment remained stable (table 3, Diagram 1).
Table 3.- Dynamics of the severity index of the DR (M ± m)
before treatment after treatment after a month after 3 months after 6 months
Control group (n = 65) 7.9 ± 0.4 6.7 ± 0.5 6.7 ± 0.5 7.8 ± 0.5 9.8 ± 0.5*
I main group (n = 63) 7.7 ± 0.3 5.04 ± 0.5** 4.5 ± 0.5** 5.4 ± 0.5** 5.7 ± 0.5*
II main group (n = 69) 8.2 ± 0.5 3.7 ± 0.4** 3.04 ± 0.4** 3.05 ± 0.4** 3.2 ± 0.4**
Note. n is the number of eyes; * p < 0.05 ** p < 0.01 - reliability of differences relative to indicators before treatment
Diagram 1. Dynamics of the severity index of DR in the study groups Hemodynamic parameters also significantly improved in the I and II major groups (Table 4).
Table 4.- Dynamics of blood flow in the eye vessels (M ± m) during treatment
I main group (n = 63) II main group (n = 69) Control group (n = 65)
Index before treat- after treat- before treat- after treat- before treat- after treat-
ment ment ment ment ment ment
1 2 3 4 5 6 7
CRA: V. sm/s s 10.1 ± 1.3 13.5 ± 0.9* 9.96 ± 0.27 13.2 ± 0.5** 10.9 ± 1.2 12.9 ± 1.4
To confirm the prognostic value of the developed dynamics of the index of severity of retinopathy in the risk of progression, a correlation analysis of the IRP and long-term observation period was performed (Table 6).
Table 6.- Correlation interrelations between the studied indicators
1 2 3 4 5 6 7
RI 0.89 ± 0.04 0.65 ± 0.03** 0.71 ± 0.02 0.65 ± 0.02* 0.91 ± 0.06 0.78 ± 0.06
PSCA: V. sm/s 10.3 ± 0.9 13.5 ± 1.2* 10.22 ± 0.7 13.8 ± 0.4* 11.2 ± 1.2 12.5 ± 0.8
RI 0.82 ± 0.03 0.64 ± 0.03** 0.81 ± 0.02 0.65 ± 0.07* 0.84 ± 0.04 0.77 ± 0.06
OA: V. sm/s 30.6 ± 2.2 37.5 ± 2.5* 30.33 ± 2.4 38.6 ± 2.6* 32.6 ± 4.1 35.3 ± 3.5
RI 0.85 ± 0.03 0.76 ± 0.03* 0.82 ± 0.04 0.72 ± 0.03* 0.83 ± 0.01 0.75 ± 0.07
Note: n is the number of eyes; * p < 0.05, ** p < 0.01 - reliability of differences relative to indicators before treatment.
According to the above-identified correlation, a risk index for the progression of diabetic retinopathy was developed and calculated based on the blood flow velocity in the main arteries of the eye before and after treatment: IRP = Vs before treatment / Vs after treatment. The ratio of these factors in dynamics can be considered as a prognostic criterion for the risk of progression of DR (Table 5).
Table 5.- The index of the risk of progression (IRP) of diabetic retinopathy in patients of three groups (n = 197), (M ± m)
With a progression risk index of less than 1.0, the course of nonproliferative diabetic retinopathy is favorable, with an incidence greater than or equal to 1.0, an unfavorable with progression. As can be seen from the table, the most effective treatment is the inclusion of en-donasal electrophoresis with tanakan.
Группы IRP DR on CRA(Vs before treatment/Vs after treatment) IRP DR on PSCA(Vs before treatment/Vs after treatment IRP DR on OA (Vs before treatment/Vs after treatment
Control group (n = 65) 1.4 ± 0.01 1.32 ± 0.01 1.89 ± 0.02
I main group (n = 63) 0.85 ± 0.01 0.91 ± 0.01 0.73± 0.02
II main group (n = 69) 0.53 ± 0.01 0.54± 0.01 0.58 ± 0.01
Progression risk index The difference in the severity index of the DR before the treatment and 6 months after the treatment Coefficient correlations (r)
IRP VCS A DR after 6 months 0.63 ± 0.05
IRP VOCCA A DR after 6 months 0.75 ± 0.04
IRP VGA A AP after 6 moths 0.72 ± 0.05
Note: ADR - ophthalmologic signs of progression of DR: the difference of the ISDR in 6 months after treatment and before treatment.
As can be seen from the table, there is a direct moderate correlation between the IRP calculated from the maximum systolic blood flow velocity in the CRA. and ADR, and a strong direct correlation was found between the IRP, calculated from the maximum systolic blood flow velocity in the PSCA and OA and the ophthalmological signs of the progression of retinopathy ADR. This indicated that the higher the calculated IRP, the more signs of progression of DR in the long-term period. Thus, the re-
sults confirm the prognostic significance of the proposed risk index for the progression of diabetic retinopathy.
Conclusions:
1. Dopplerographic criteria for the staging of NDR have been established: a decrease in the maximum systolic blood flow velocity in the C^A, PSCA and OA corresponds to an increase in the severity of DR. Based on clinical studies and duplex mapping of the vessels of the eye, inverse correlativ links between blood flow veloci-
ties in C^A PSCA and OA and the severity index of DR were revealed, which made it possible to determine the prognostic significance of the studied factors as markers and predictors of progression of the DR.
2. Improving the rheological properties ofblood with tanakan prevents damage to the vascular endothelium in the time of increasing blood flow in the initial stage of NDR and improves the perfusion of retinal tissues in all stages of NDR. In the second and third stages of NDR,
after treatment with tanakan in the form of endonasal electrophoresis, the speed and volume blood flow in the retinal vessels increases.
3. The developed IRP DR, based on the ratio of the maximum systolic velocities of the C^., PSCA and OA before and after treatment (Vs after treatment / Vs before treatment) allows to evaluate the effectiveness of the treatment, as well as predict the development ofvascular changes and the progression of DR.
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