Доклад Курышевой Наталии на VII Мировом конгрессе по глаукоме (English)

31.07.2017

A report by Kurysheva N.31.06 (WGC, Helsinki)

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The disturbances of blood supply to the optic nerve are involved in difference forms of ophthalmopathology: diabetic retinopathy, artery and vein occlusion and Neurodegenerative disorders, including glaucoma

 

One should keep in mind, that blood supply to ON is complex and is derived from Central retinal artery, cilliary arters that are responsible for the blood supply to the laminar and prelaminar part and the choroid, which has special anatomical and physiological properties.

 

Finally one should remember that a great number of ganglion cells of the axons are located in macula. It has been assumed that the inferior part of macula as well as the inferior part of the peripapillary retina are very susceptible to ischemia. And this is a possible but  not   a proved  reason of early involvement of  macula in glaucoma which can be missed at the early stages of the disease.

 

Recently we revealed that the parameters of blood flow in the eye measured by CDI had the advantages over structural and functional parameters in detection of pre-perimetric glaucoma. First of all it concerned the venous circulation and the choroid.

According to the recent literature review structural variables  (first of all the average of RNFL thickness) measured by OCT  have   the best diagnostic  accuracy both for early glaucoma detection and its monitoring.

 

Recent studies have also suggested that glaucomatous damage frequently affects the macular region first and D. Hood  described  the macular vulnerability zone. However its early involvement in glaucoma has not ben understood yet. One should keep in mind that a great number of ganglion cells of the axons are located in macula. It has been assumed that the inferior part of macula is very susceptible to ischemia. And this is a possible but  not   a proved  reason of early involvement of  macula in glaucoma.

 

Recently we revealed that the parameters of blood flow in the eye measured by CDI had the advantages over structural and functional parameters in detection of pre-perimetric glaucoma.

First of all it concerned the venous circulation and the choroid.

However CDI doesn’t allow to investigate the microcirculation of the retina and ONH

The appearance of the new method- OCTA- has riced once again the question…Does Blood Flow measurement have a role in glaucoma care?

 

 

Jia et al developed a speci c algorithm for OCTA called splitspectrum amplitudedecorrelation angiography (SSADA). The algorithm is based on the variation of reflectance amplitude which is sensitive to motion and flow in all directions. They recruited 4 preperimetric glaucoma patients and four normal subjects in order to obtain ONH blood flow with OCTA. They found that in early glaucoma the reduction of ONH microvascular flow was much more dramatic than that of whole ONH circulation.

 They suggested that quantication performed on microvascular perfusion might be sensitive for detecting ONH circulatory changes in early glaucoma patients.

 Then first publication came from the authors of this method who described the reduction of ONH perfusion in PPG compared to normal eyes. In a separate study, Jia et compared the optic disc perfusion between 24 normal subjects and 11 patients with glaucoma using SSADA technology. They demonstrated that OCTA can detect reduced disc perfusion in a group of patients with early glaucoma . They emphasized that this reduction in flow index is not a result of rim loss or cupping in glaucomatous eyes, and they showed a strong link between the disc fow index and the visual field pattern standard deviation. with 100% sensitivity and specificity.

Lee et al:   Peripapillary flow index and peripapillary vessel density in glaucomatous eyes were significantly lower than those in normal eyes and were

They found that decreased vessel density was significantly associated with the severity of glaucoma.

 

 

The relation between ONH BF and structural and functional loss in glaucoma was emphasized by Leveque . They also observed a significant correlation between ONH perfusion and structural and functional glaucoma damage.

 

 

Chen  investigated optic disc perfusion differences in normal, primary open-angle glaucoma (POAG), and normal tension glaucoma (NTG) eyes using optical microangiography (OMAG). This is a modification of (OCT) angiography technique. Using

semi-automatic segmentation program the authors succeeded in measuring the vessel density in the pre-laminar layer.

Glaucomatous eyes had significantly lower optic disc perfusion in preLC which correlated with structural and functional parameters in glaucoma compared to normal eyes.  But they didn ‘t find the difference between the glaucomatous groups.

 

According to the multicenter International Study The vessel density measured  both in ONH and in Peripap.Retina (so called: Whole En Face Image) has the priority over RNFLT in discriminating the Normal, Glaucoma suspect and Glaucoma Eyes.

All vessel density measurements showed a stepwise decrease from normal eyes to preperimetric glaucoma eyes to glaucoma eyes.

 

They found that vessel density had diagnostic accuracy similar to RNFL thickness measurements for differentiating between healthy and glaucoma eyes.

 

The study suggested that retinal vascular changes may develop early in the glaucomatous process.

They concluded that OCTA is a promising technology in glaucoma management, potentially enhancing the understanding of the role of vasculature in the pathophysiology of the disease.

 

The amount of papers on OCTA in glaucoma is growing each month. The authors try to improve the reliability of the method in order to visualize better the small vessels of ONH.

and introduce there own semi-automatic segmentation programs to measure the vessel density in different areas for example – of preLC LC (like Chen and co-auth.).

 

Suh et al showed that OCTA measured vessel density was significantly lower in POAG eyes with focal LC defects than in eyes without LC defect. The reduction of vessel density was also found to be spatially correlated with the location of the LC defect. easurements were comparable to RNFL measurements in both POAG and PACG.

Annular capillary density was also signi cantly reduced in the POAG group when compared to the NTG group.

In addition, peripapillary vessel densities have been reported to be significantly reduced at the corresponding location of the visual field defects and highly correlate with visual field pattern standard deviation.

They found that the diagnostic ability of peripapillary vessel density parameters of OCTA, especially the inferotemporal sector measurement, was good in POAG and PACG. Diagnostic abilities of vessel density

 

One can notice that all the researches paid attention only to optic NH and PPR, besides hey didn’t stop the administration of hypotensive eye drops though they can influence the blood circulation. 

Recently we compared the results of OCT-A in glaucoma with parameters of retrobulbar  blood flow measured by CDI and structural and functional variables, measured by OCT, perimetry and by electrohhisiological methods (Pattern electroretinogram and Visual Evoked Potentials).

 

Patients with early and advanced glaucoma were compared with each other and with normal subjects. 109 parameters were investigated in this study for each eye (including the RNFL , GCC and the choroidal thickness as well as the ocular perfusion pressure.

We stopped hypotensive eye drops three weeks before the examination.

 

The density of the ONH vessels was measured in the ONH and peripapillary area (750-μm-wide elliptical annulus extending from the optic disc boundary in the layer of 100 μm thickness from ILM)/ The peripapillary , which was divided into 6 sectors as shown here,  And using of Grid-Based algorithm (shown in color map here).

…And also in macula: in  fovea (1 mm around the center) and parafovea (in the area between the foveal border and a circumference 3 mm in diameter) in superficial and deep capillary plexuses that are shown with red lines in this slide..

 

We revealed a statistically significant reduction of all the parameters of OCTA in glaucomatous eyes compared to normal eyes. It concerned both the ONH and PPR and macula.

The more severe glaucoma was, the lower parameters were obtained as shown here.

In this graphs the cutoff value for the. most important parameters are represented.

 

The reduction of Vessel Density corresponded with structural and functional damage which was especially notable in the PPR in advanced glaucoma as it is shown in these examples.

 

In regard to the early glaucoma detection it was macula area where the reduction of vessel density preceded structural and functional loss. In this slide it is clearly visible in the color map of vessel density

This is a clinical example of advanced glaucoma: the correspondence between the very pronounced reduction vessel density in the inftemp perip retina, the extremely low End Diastolic Velosity in the Ophthalmic Artery and  the reduction of the perip. choroidal thickness are clearly shown as well as the decrease of the amplitude of component P100 of VEP elicited by stimulus  with large 1 degree (°) and small 0.25° checks.  

 

In contrast to our results the Indian authors recently reported  about the  priority of PPR VD over macula VD in the early glaucoma detection. We explain this by the more severe glaucoma stage of the patients that were recruited in this study.

 

According to our data as it is clearly shown in In these ROC curves (Areas under the receiver operating characteristic curves (AUROC)

the measurement of  Vessel  density in  macula has an advantage over the ON vessel density in distinguishing early glaucoma from the norms.

Meanwhile in discrimination  between the glaucoma stages structural parameters had the highest value, especially in Infer. Temporalis PPR. Interestingly that in regard to OCTa  the vessel density in the same area was very important.

 

In conclusion: OCT-A is a new perspective method for glaucoma diagnostics. Will it become “number one» or only like an ancillary method in future? To answer this question more studies are required. 


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