UDC 616.7.-007.681-085.27:577.112.385:617.735/.736-018.82-07

https://doi.org/10.31288/oftalmolzh201542327

THE THICKNESS OF THE RETINAL GANGLION CELLS COMPLEX (GCC) AND NERVE FIBERS IN THE MACULAR AREA IN PATIENTS WITH PRIMARY OPEN-ANGLE GLAUCOMA (POAG) THAT RECEIVED L-ARGININE IN TERMS OF THEIR TREATMENT

Gonchar’ E. N.PhD student of the Departmentof Ophthalmology of Kharkiv National Medical University (KNMU)

The Departmentof Ophthalmology of Kharkiv National Medical University (KNMU)

E-mail: elena.n.gonchar@gmail.com

Introduction. In accordance with the contemporary concept, the nature of the glaucomatous damage lies in the accelerated loss of retinal ganglion cells and their axons as optic nerve components, which is associated with the neurons neurotrophic defense reduction, the breach of encephalitic trophic factors transportation to the retinal ganglion cells, as well as with neuroglia involvement, which ensures the optic nerve nutrition.

Objective: the study of the thickness of the retinal ganglion cells complex (GCC) and nerve fibers in the macular area in patients with primary open-angle glaucoma (POAG), which received L-arginine in terms of their treatment.

Material and Methods: 109 patients (192 eyes) with POAG were examined in terms of the study. The patients’ age ranged from 40 to 87 years. All patients were randomized into two groups: index treatment group and control group. The index group consisted of 60 patients (102 eyes) with POAG, which received L-arginine treatment along with the background therapy (in accordance with our own proposed scheme ? UA 52177 U Ukrainian patent license). The control group consisted of 49 patients (90 eyes) with POAG that received the background therapy. The examination included conventional ophthalmic examination techniques, as well as static computer perimetrium and optical coherence tomography (OCT).

Results: It has been established that in patients with POAG that received L-arginine in their treatment, the long-term period stabilization frequency of the nerve fibers average thickness in the macular area was 16% higher than that of the control group (71.6% and 55.6%, respectively), the stabilization frequency of the retinal ganglion cells complex (GCC) average thickness was 23.1% higher than that of the control group (85.3% and 62.2%, respectively), the stabilization frequency of retinal ganglion cells complex (GCC) average thickness in the lower part was 24.6% higher than that of the control group (82.4% and 57.8%, respectively), and the differences were reliable for all parameters (p<0.05).

Conclusion: The L-arginine use in the treatment of patients with POAG (primary open-angle glaucoma) contributes to the long-term period stabilization of retinal ganglion cells complex (GCC) average thickness, as well as its thickness in the lower part and the macular area nerve fibers thickness.

Keywords: primary open-angle glaucoma, L-arginine, retinal ganglion cells complex (GCC) thickness, nerve fibers thickness in the macular area.

Introduction. In accordance with the contemporary concept the nature of the glaucomatous damage lies in the accelerated loss of retinal ganglion cells and their axons [1, 8, 16], as optic nerve components, the main reason of which is associated with the neurons neurotrophic defense reduction, encephalitic trophic factors transportation breach to the retinal ganglion cells, as well as with neuroglia involvement, which ensures the optic nerve nutrition [5, 6, 7].

Liesegang T. J.publishedhistological andelectrophysiologicalevidence proving thatretinalganglion cellsare the soleneurons that suffer fromglaucoma [14].

Therefore one can hopethatneuroprotectivetherapy, which prevents the retinal ganglion cells destruction, willcontribute to the stabilizationof visual functionsin patients withprimary open-angle glaucoma(POAG).

Taking into accountthat L-arginine reduces theintraocular pressurein healthy individuals [10], relievesvasospasm [15] and helps to reducethe destruction ofretinal ganglion cellsin terms of experimentaldisturbed circulation [9], its use intreating patients withprimary open-angle glaucomamay be promising.

Objective of the present work lies in the study of the thickness of the retinal ganglion cells complex (GCC) and nerve fibers in the macular area in patients with primary open-angle glaucoma (POAG), which received L-arginine in terms of their treatment.

Material and Methods: The thickness of the retinal ganglion cells (GCL), their thickness in the lower layer (GCL Inf), as well as the thickness of the nerve fibers in the macular area (NFL Th) were studied by means of optical coherence tomography (OCT) technique using the TOPCON 3D OCT-1000 device with the involvement of  109 patients (192 eyes) with POAG. The patients’ age ranged from 40 to 87 years. The average age ofthe patients was(64.2 ± 5.9)years.

All patients were randomized into two groups: index treatment group that consisted of 60 patients (102 eyes) and control group that consisted of 49 patients (90 eyes) with first, second and third stages of POAG. Patients with the fourth stage of POAG and high degree of ametropy were eliminated from the study. All patients received the background therapy (vasoprotectors, antioxidants, vitamins) and antihypertensive therapyaccording to the protocolof medicalcare provision to patients withPOAG (OrderNo 117of the Ministry of Health of Ukraine,dated March15, 2007). All patients had the normalization ofintraocular pressure (IOP) before and during the treatment as well as within the 6months post-treatment period. The index group patients received L-arginine treatment along with the background therapy in accordance with our own proposed therapeutic regimen (UA 52177 U Ukrainian patent license).

Neither one of the patientsin both index and control groupswas diagnosed with the optic nerve diseases, hypertensiveangiopathy, ocular media deficiency that could complicate the OCT procedure conducting. Patientsin both groupswere comparableby gender and age regarding the receivedantihypertensive therapy(p> 0.05). In accordance with the identified visual organ co-morbidity the patients were divided as follows: mild myopia (index group – 19, control group – 16 eyes); moderate myopia (index group – 12, control group – 11 eyes); low degree hypermetropia (index group – 16, control group – 14 eyes).

The examination of patientswithPOAGincluded conventional ophthalmic examination techniques: visometry, tonometry according toMaklakov, pneumotonometryandpachymetrywith the definition ofthe trueintraocular pressure, biomicroscopy,ophthalmoscopy, as well as static computer perimetrium (in accordance with the 30-2 program). The optical coherence tomography (OCT) was performedbefore the treatment, after the treatment(in 1month), as well as in the long term period (in 6 months). Before the OCT executing all patients underwent refractive keratoplasty, the data of which were introduced intothe research protocol afterwards, and were automatically recalculated. Thus, it prevented thepossibility of the analogue picturedistortion orunreliable results obtaining.

Statistical analysiswas performed using ‘Statistica 6.0’ (StatSoft Inc.,USA)application software. Nonparametric tests, Student criterion(t) and linearcorrelation analysis were used to determine thesignificance of differencesin comparable groups. The level of significance of the differences р<0.05 was recognized as critical.

Results and discussion. The distribution of patientsaccording to the POAG stagesis shown in Table1, the data of which shows that there was no statistical difference inthe proportion of the distribution ofeyeswith different stages ofPOAGin theindex and control groups.

                                                                                                                    Table 1 The distribution of patientsaccording to the stagesof POAGin theindex and control groups

Note: n –quantity of eyes, р –level of significance of the differences

It is established that in one month after the treatment the average thickness of the retinal ganglion cells complex (GCC) in patients with POAG of the index and control groups has not significantly changed. In the index group patients, which received L-arginine in terms of their treatment, the given indicatorbefore and after treatmentamounted to (64.45±1.49) millimicron and (64.59±1.58) millimicron, respectively (р>0.05). In the control group patients the average thickness of the retinal ganglion cells complex (GCC) decreased from (61.35±1.58) millimicron to (60.19±1.66) millimicron (р>0.05).

It is shown thatin patients withPOAG thatreceivedL-arginine as a part of their treatment the frequency of the retinal ganglion cells complex (GCC) average thicknessstabilization was95.1% andwas higher thanthe same indicatorin the control group(91.1%) by 4.0%, but the differencesbasically had the nature of trend(p> 0.05).

The retinal ganglion cells complex (GCC) average thickness in the lower part in patients withPOAG in both study groups alsodid not changesignificantly, in the index groupbefore and after the treatmentitamounted to (64.46±1.85) millimicron and (64.89±1.87) millimicron, respectively (р>0.05), and in the control group it reduced from (65.61±1.81) millimicron to (64.12±1.89) millimicron (р>0.05).

It has been established that in patients of the index group that received L-arginine as a part of their treatment the stabilization frequency of the retinal ganglion cells complex (GCC) average thickness in the lower part (86.3%) was higher thanthis indicatorin the control group(83.3%) by 3.0%(the differencesbetween the groupsbasically had the nature of trend, p> 0.05).

Overall,regarding the group,the average thickness ofthe nerve fibersin the macular area in patientsof both groupswas not significantlychanged. In the index group the given indicatorbefore and after the treatmentamounted to (28.12±1.05) millimicron and (27.64±1.08) millimicron, and in the control group it amounted to (30.90±1.08) millimicron and (30.11±1.11) millimicron, respectively (р>0.05).

The stabilization frequency of the nerve fibers average thickness in the macular area immediately following the treatment in patients of the index group was86.3% of eyes and was higher than the given indicatorin the control group (85.6% of eyes) only by 0.7% (the differencesbasically had the nature of trend, р>0.05).

When analyzing the resultsof the researchin the long-term periodfollowing the treatment(in 6 months) it has been established that in patients with POAG that receive L-arginin as part of their treatment the stabilization frequency of the retinal ganglion cells complex (GCC) average thicknesssignificantlydecreased by9.8% (p <0.05)incomparison with the indicator received immediatelyafter the treatment. At the same time, the stabilization frequency of the retinal ganglion cells complex (GCC) average thicknesssignificantlyexceeded thegiven indicatorby 23.1%in the control group(85.3% and62.2%, respectively, p <0.05) (Table. 2).

                                                                                                                     Table 2 The stabilization frequency of the retinal ganglion cells complex (GCC) average thickness, its thickness in the lower part and fibers thickness in the macular areain patients with POAGin the long-term periodfollowing the treatment

Note: n –quantity of eyes, р –level of significance of the differences; the retinal GCC – the retinal ganglion cells complex; POAG – primary open-angle glaucoma.

It has also been established that in the long-term period following the treatments (in 6 months) in patients with POAG, which received L-arginin as a part of their treatment, the stabilization frequency of the GCC average thickness in the lower part (82.4%) decreased insignificantly (by 4.8%, p>0.05) in comparison with indicatorsimmediately aftertreatment, but was significantlyhigher thanthe said indicator(24.6%) in the control group(57.8%, p <0.05).

The stabilization frequency of the nerve fibers average thickness in the macular area significantlydecreased to71.6% (p <0.05) in patients of the index group incomparisonwith the indicatorimmediately followingthe treatment, butitexceededthe indicatorin the control group(55.6%) by16.0% (p <0.05).

It should be notedthat a gradualdecrease in GCC density is typicalfor experimentalmodelsof glaucomacaused, in particular, by the IOPperiodic increase [12]. Also,significant differences regarding the retinal ganglion cells complex (GCC) indicators have been identifiedin glaucoma patientscompared with the healthy individuals [1].

Recent studies showthat the determinationof the structural parametersof the retinain the macular areaby means ofOCT is not inferior to the studies of the thickness ofthe optic nerveperipapillarynerve fibersin regard to the glaucomadiagnostic accuracy [11, 17, 18, 19]. According to Kim N. R. et al. (2010) the data on the retinal ganglion cells complex (GCC) allowto detectglaucomaat earlier stages, in comparisonwith the thickness ofperipapillarynerve fibers [13].

The decrease in the stabilization frequency of the average thickness of retinal ganglion cells complex (GCC) and the nerve fibers thickness in the macular area in the long-term period, which we have established, both in theindex andin the control groups,is consistentwith the opinion ofZavgorodniaia N. G.andPasechnikova N. V. (2010) and other authorsregarding the permanentprogression ofPOAG, regardless of the treatment [3, 4].

At the same time, in the long-term period the stabilization frequencyofall studiedindicators after the treatmentwith the use of L-argininein patients withPOAGwas significantly higherin comparisonwith the control group.

We have obtainedimmediate andlong-term results of treatment using L-arginine in patients with POAG that to a certain degree are confirmed by Chuman H. et al.studies(2013), which showedthat the use ofL-arginine in experimentaldisturbed circulationrestored the lowered threshold of the scotopicsensitivity, as well as reducedthe destruction of the retinal ganglion cells [9].

Conclusion: Thus, L-arginine use in the treatment of patients with POAG (primary open-angle glaucoma) contributes to the stabilization of the average thickness of retinal ganglion cells complex (GCC) in the long-term period, as well as its thickness in the lower part and the thickness of the nerve fibers in the macular area.

Our findingsnot onlyshow the effectiveness of L-arginine in patients withPOAG treatment, but also open upthe prospects of furtherstudies of itsneuroprotectiveproperties.

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