Morphological functional criteria of neuroprotective therapy efficacy in glaucomatous optic neuropathy

Electrophysiological tests may be used to detect early glaucomatous changes and glaucoma progression risk and to monitor treatment efficacy. Most important pathogenic aspects of glaucomatous process, pathogenesis and multifactorial nature of glaucomatous optic neuropathy are described. Major triggers of glaucomatous optic neuropathy are mechanical and vascular. Principles of neuroprotective therapy, neuroprotective drugs, and mechanisms of action of direct and indirect neuroprotective agents are presented. IOPcc is a basis for neuroprotective therapy selection and its efficacy monitoring. Amongst neuroprotective drugs, NMDA agonists, antioxidants, peptides, and calcium channel blockers are of special importance. Structural damage and functional deficiency (e.g., visual field loss) in glaucoma and the most informative and accurate methods of their detection are characterized. Confocal laser microscopy, optical coherence tomography, and scanning laser polarimetry are compared. These techniques are used to study optic nerve head and retinal nerve fiber layer. They are proposed as diagnostic and monitoring tools for glaucoma, glaucoma suspicion, and ocular hypertension. The most sensitive and specific electrophysiological tests for glaucomatous optic neuropathy are pattern electroretinography, multfocal electroretinography, and multifocal visually evoked potentials. 

1. Kurysheva N. I. [Glaucomatous optic neuropathy]. Glaukomnaja opticheskaja nejropatija. Мoscow, MEDpress-inform; 2006. (in Russ.).

2. Nesterov A. P. [Glaucoma]. Glaukoma. Мoscow, MIA, 2008. (in Russ.).

3. Avetisov S.E., Egorov E.A., Moshetova L.K., Neroev V.V., Takhchidi Kh.P. [Ophthalmology: National guidelines]. Oftal’mologija: Nacional’noe rukovodstvo. Мoscow, GEOTAR-Media, 2008. (in Russ.).

4. Schacknow P.N., Samples J.R. The glaucoma book: a practical, evidence-based approach to patient care. NewYork, Springer; 2010.

5. Fedorov S.N., Ivashina A.I., Mihaylova G.D. [Pathogenesis and treatment of glaucoma]. Voprosy patogeneza i lechenija glaukomy. Мoscow, 1981. (in Russ.).

6. Nesterov A.P., Cherkasova I.N. [The role of risk factors in open-angle glaucoma diagnostics]. Rol’ faktorov riska pri diagnostike otkrytougol’noj glaukomy. [Annals of Ophthalmology]. Vestnik oftal’mologii. 1987; 103 (5): 18-20. (in Russ.).

7. Boland M.V., Quigley H.A. Risk factors and open-angle glaucoma: classification and application. J. Glaucoma. 2007; 16 (4): 406-418.

8. Coleman A.L., Miglior S. Risk factors for glaucoma onset and progression. Surv. Ophthalmol. 2008; 53 (1): 3-10.

9. De Moraes C.G., Juthani V.J., Liebmann J.M., Teng C.C., Tello C, Susanna R.Jr., Ritch R. Risk factors for visual field progression in treated glaucoma. Arch. Ophthalmol. 2011; 129 (5): 562-568.

10. Ekstrom C. Risk factors for incident open-angle glaucoma: a population-based 20-year follow-up study. Acta Ophthalmol. 2012; 90 (4): 316-321.

11. Leske M.C., Wu S.Y., Hennis A., Honkanen R., Nemesure B., Group BES. Risk factors for incident open-angle glaucoma: the Barbados Eye Studies. Ophthalmology. 2008; 115 (1): 85-93.

12. Topouzis F., Wilson M.R., Harris A., Founti P., Yu F., Anastasopoulos E., Pappas T., Koskosas A., Salonikiou A., Coleman A.L. Risk factors for primary openangle glaucoma and pseudoexfoliative glaucoma in the Thessaloniki Eye Study. Am. J. Ophthalmol. 2011; 152 (2): 219-228.

13. Yanagi M., Kawasaki R., Wang J.J., Wong T.Y., Crowston J., Kiuchi Y. Vascular risk factors in glaucoma: a review. Clin. Ex. Ophthalmol. 2011; 39 (3): 252-258.

14. Volkov V.V. [Open angle glaucoma]. Otkrytougol’naja glaukoma. Мoscow, MIA, 2008. (in Russ.).

15. ShmyrevaV.F. [Risk factors and target pressure in glaucomatous optic neuropathy]. Faktory riska i celevoe vnutriglaznoe davlenie pri glaukomnoj opticheskoj nejropatii. [Glaucoma: reality and perspective: collection of scientific papers] Glaukoma: real’nost’ i perspektivy: sb. nauch. statei. Мoscow, 2008. (in Russ.).

16. Volkov V.V. [Glaucoma with pseudo-normal intraocular pressure]. Glaukoma pri psevdonormal’nom davlenii. Мoscow, Medicine, 2001. (in Russ.).

17. Nucci C., Tartaglione R., Rombola L., Morrone L.A., Fazzi E., Bagetta G. Neurochemical evidence to implicate elevated glutamate in the mechanisms of high intraocular pressure (IOP) — induced retinal ganglion cell death in rat. Neurotoxicology. 2005; 26 (5): 935-941.

18. Sharma S.C. Cell death in glaucoma. Arch.Soc. Esp. Oftalmol. 2000; 75 (3): 141-2.

19. Krasnov M.M. [Intraocular blood flow]. O vnutriglaznom krovoobrashhenii pri glaukome. [Annals of Ophthalmology]. Vestnik oftal’mologii 1997; 113 (5): 5-7. (in Russ.).

20. Kugoeva E. E., Podgornaja N. N., Sherstneva L. V. [Eye hemodynamics and somatic status research in patients with primary open angle glaucoma]. Izuchenie gemodinamiki glaza i obshhesomaticheskogo statusa bol’nyh s pervichnoj otkrytougol’noj glaukomoj. [Annals of Ophthalmology]. Vestnik oftal’mologii 2000; 116 (4): 26-27. (in Russ.).

21. Shmyreva V. F., Petrov S. Yu., Antonov A. A., Stratonnikov A. A., Savel’eva T. A., Shevchik S. A., Ryabova A. A. [The research of metabolism of the anterior eye segment according to hemoglobin oxygenation levels in the venous bed in patients with primary open angle glaucoma]. Issledovanie metabolizma tkanej perednego otrezka glaza po urovnju oksigenacii gemoglobina v venoznom rusle pri pervichnoj otkrytougol’noj glaukome. [Glaucoma]. Glaukoma. 2008; 3: 3-10. (in Russ.).

22. Egorov E. A., Egorov A. E., Brezhnev A. Yu. [Modern aspects of glaucoma neuroprotective treatment]. Sovremennye aspekty nejroprotektornoj terapii glaukomy. Мoscow, April’, 2014. (in Russ.).

23. Shields M. B., Tombran-Tink J., Barnstable C. J. Mechanisms of the glaucomas: disease processes and therapeutic modalities. Totowa, NJ: Humana Press: Springer distributor; 2008.

24. Avetisov S.E., Bubnova I.A., Petrov S.Yu., Antonov A.A. [The role of corneal resistance factor, defined by means of bidirectional pneumoapplanation, in tonometry assessment]. Znachenie faktora rezistentnosti rogovicy, opredeljaemogo metodom dvunapravlennoj pnevmoapplanacii, v traktovke rezul’tatov tonometrii. [Glaucoma]. Glaukoma. 2012 (1): 12-15. (in Russ.).

25. Akopyan A.I., Erichev V.P., Iomdina E.N. [The role of of biomechanical properties of the eye in the assessment of the progression of glaucoma, myopia and combined pathology]. Cennost’ biomehanicheskih parametrov glaza v traktovke razvitija glaukomy, miopii i sochetannoj patologii. [Glaucoma]. Glaukoma. 2008; 1: 9-14. (in Russ.).

26. Vodovozov A.M., Boriskina M.G. [True target pressure in patients with glaucoma,cular hypertension and normal-pressure glaucoma]. Istinnoe tolerantnoe vnutriglaznoe davlenie pri glaukome, glaznoj gipertenzii i glaukome s nizkim davleniem. [Annals of Ophthalmology]. Vestnik oftal’mologii. 1989; 105 (1): 5-7. (in Russ.).

27. Avetisov S. E., Mamikonyan V. R., Kazaryan E. E., Shmeleva-Demir O. A., Mazurova Yu. V., Ryzhkova E. G., Antonov A. A., Tatevosyan A. A. [New screening method of defining target pressure]. Novyj skriningovyj metod opredelenija tolerantnogo vnutriglaznogo davlenija. [Annals of Ophthalmology]. Vestnik oftal’mologii. 2007; 5: 3-7. (in Russ.).

28. Avetisov S. E., Bubnova I. A., Petrov S. Yu., Antonov A. A., Reshhikova V. S. [Specifics of the biomechanicas properties of the fibrous layer of the eye in patients with primary open-angle glaucoma]. Osobennosti biomehanicheskih svojstv fibroznoj obolochki glaza pri pervichnoj otkrytougol’noj glaukome. [Glaucoma]. Glaukoma. 2012; 4: 7-11. (in Russ.).

29. Erichev V. P., Eremina M. V., Yakubova L. V., Aref’eva Yu.A. [The analyzer of biomechanicas properties of the eye in the assessment of viscoelastic properties of the cornea in healthy eyes]. Analizator biomehanicheskih svojstv glaza v ocenke vjazko-jelasticheskih svojstv rogovicy v zdorovyh glazah. [Glaucoma]. Glaukoma. 2007; 1: 11-15. (in Russ.).

30. Avetisov S. E., Bubnova I. A., Antonov A. A. [Once more on the diagnostic capability of elastotonometry] Eshhe raz o diagnosticheskih vozmozhnostjah jelastotonometrii. [Annals of Ophthalmology]. Vestnik oftal’mologii 2008; 5: 19-22. (in Russ.).

31. Аvetisov S. E., Bubnova I. A., Antonov A. A. [The study of the effect of the corneal biomechanical properties on the intraocular pressure measurement]. Issledovanie vliyaniya biomehanicheskih svoistv rogovicy na pokazateli tonometrii. [Bulletin of the Siberian Branch of the Russian Academy of Medical Sciences]. Bulleten’ Sibirskogo otdeleniya Rossiyskoi akademii medicinskih nauk. 2009; 29 (4): 30-33. (in Russ.).

32. Kozlova I.V., Akopyan A.I., Reshhikova V.S. [Administration of Betoftan 0,5% in patients with primary open-angle glaucoma] Primenenie preparata betoftan 0,5% u bol’nyh pervichnoj otkrytougol’noj glaukomoj. [Glaucoma]. Glaukoma. 2011; 2: 17-20. (in Russ.).

33. Kozlova I. V., Akopjan A. I., Reshhikova V. S. [The use of new fixed form of Dorzopt plus in treatment of patients with primary open-angle glaucoma]. Opyt primenenija novoj fiksirovannoj formy dorzopt pljus v lechenii pacientov s pervichnoj otkrytougol’noj glaukomoj. [Glaucoma]. Glaukoma. 2012; 2: 50-54. (in Russ.).

34. Egorov A. E., Obruch B. V., Kasimov E. M. [The use of Mexidol in patients with optic neuropathies]. Primenenie Meksidola u bol’nyh s opticheskimi nejropatijami. [Clinical Ophthalmology]. Klinicheskaja oftal’mologija. 2002; 3 (2): 28-31. (in Russ.).

35. Alekseev V.N., Morozova N.V. [The use of Retinalamin in patients with primary open-angle glaucoma]. Primenenie Retinalamina u bol’nyh s pervichnoj otkrytougol’noj glaukomoj. [Glaucoma]. Glaukoma. 2013; 1: 49-52. (in Russ.).

36. Kamenskih T. G. [Clinical research of parabulbar and subtenon Retinalamin in patients with open-angle glaucoma]. Klinicheskoe issledovanie dejstvija preparata «Retinalamin» u bol’nyh otkrytougol’noj glaukomoj pri parabul’barnom i subtenonovom vvedenii. [Clinical Ophthalmology]. Klinicheskaja oftal’mologija. 2006; 7 (4): 142-143. (in Russ.).

37. Erichev V. P., Shamshinova A. M., Lovpache D. N. [Comparative assessment of peptide bioregulators neuroprotective action in patients with various stages of primary open-angle glaucoma]. Sravnitel’naja ocenka nejroprotektornogo dejstvija peptidnyh bioreguljatorov u pacientov s razlichnymi stadijami pervichnoj otkrytougol’noj glaukomy. [Glaucoma]. Glaukoma. 2005; 1: 18-24. (in Russ.).

38. Alekseev I.B., Lomakina O.E., Shinalieva O.N., Alekseeva G.N. [The efficacy of 0,1% Semax as neuroprotective therapy in patients with glaucoma]. Effektivnost’ ispol’zovanija preparata Semaks 0,1% v kachestve nejroprotektornoj terapii u glaukomnyh bol’nyh. [Glaucoma]. Glaukoma. 2012; 1: 48-52. (in Russ.).

39. Kurysheva N. I., Shpak A. A., Iopleva E. E. [Semax in treatment of glaucomatous optic neuropathy in patients with normal range IOP]. «Semaks» v lechenii glaukomatoznoj opticheskoj nejropatii u bol’nyh s normalizovannym oftal’motonusom. [Annals of Ophthalmology]. Vestnik oftal’mologii. 2001; 117 (4): 5-8. (in Russ.).

40. Efimova M. N., Yakubova L. B. [The effect of calcium channel blockers systemic administration on the field of vision of patients with primary open-angle glaucoma]. Neposredstvennye rezul’taty vlijanija sistemnogo priema antagonistov kal’cija na polja zrenija bol’nyh pervichnoj otkrytougol’noj glaukomoj s normalizovannym davleniem. [Glaucoma]. Glaukoma. 1994; 82-84. (in Russ.).

41. Kaiser H. J., Flammer J., Stumpfig D. [Significance of the peripheral visual field for diagnosis of glaucoma]. Klin. Monatsbl. Augenheil. 1992; 200 (1): 17-20.

42. Kuroedov A. V., Golubev S. Yu., Shafranov G. V. [The study of morphometric criteria of optic nerve head in the light of modern laser diagnostic methods]. Issledovanie morfometricheskikh kriteriev diska zritel’nogo nerva v svete vozmozhnostey sovremennoy lazernoy diagnosticheskoy tekhniki. [Glaucoma]. Glaukoma. 2005; 2: 7-18. (in Russ.).

43. Erichev V.P., Akopyan A.I. [Several correlations between retina tomography parameters]. Nekotorye korreljacionnye vzaimootnoshenija parametrov retinotomograficheskogo issledovanija. [Glaucoma]. Glaukoma. 2006; 2: 24-28. (in Russ.).

44. Toth M., Kothy P., Hollo G. Accuracy of scanning laser polarimetry, scanning laser tomography, and their combination in a glaucoma screening trial. J. Glaucoma. 2008; 17 (8): 639-646.

45. Cox T.A. Laser polarimetry in the detection of glaucoma. Ophthalmology. 2002; 109 (2): 216-217.

46. Jonas J. B., Fernandez M. C., Naumann G. O. Glaucomatous optic nerve atrophy in small discs with low cup-to-disc ratios. Ophthalmology. 1990; 97 (9): 1211-1215.

47. Bowd C., Zangwill L. M., Berry C. C., Blumenthal E. Z., Vasile C., Sanchez-Galeana C., Bosworth C. F., Sample P. A., Weinreb R. N. Detecting early glaucoma by assessment of retinal nerve fiber layer thickness and visual function. Invest. Ophthalmol. Vis. Sci. 2001; 42 (9): 1993-2003.

48. Hougaard J. L., Heijl A., Bengtsson B. Glaucoma detection by Stratus OCT. J. Glaucoma. 2007; 16 (3): 302-6.

49. Shpak A. A., Ogorodnikova S. N. [High resolution three-dimensional optic coherence tomography]. Trehmernaja opticheskaja kogerentnaja tomografija vysokogo razreshenija. [Ophthalmosurgery]. Oftal’mokhirurgiya. 2007 (3): 61-65. (in Russ.).

50. Wheat J. L., Rangaswamy N. V., Harwerth R. S. Correlating RNFL thickness by OCT with perimetric sensitivity in glaucoma patients. J. Glaucoma. 2012; 21 (2): 95-101.

51. Silva F.R., Vidotti V.G., Cremasco F., Dias M., Gomi E.S., Costa V.P. Sensitivity and specificity of machine learning classifiers for glaucoma diagnosis using Spectral Domain OCT and standard automated perimetry. Arq. Bras. Oftalmol. 2013; 76 (3): 170-174.

52. Cvenkel B., Kontestabile A.S. Correlation between nerve fibre layer thickness measured with spectral domain OCT and visual field in patients with different stages of glaucoma. Graefe’s archive for clinical and experimental ophthalmology. Graefes Arch. Clin. Exp. Ophthalmol. 2011; 249 (4): 575-584.

53. Shamshinova A. M., Volkov V. V. [Functional diagnostic techniques in ophthalmology]. Funkcional’nye metody issledovanija v oftal’mologii. Мoscow, Medicine, 1998. (in Russ.).

54. Egorova I. V., Shamshinova A. M., Erichev V. P. [Functional studies in glaucoma diagnostics]. Funkcional’nye metody issledovanija v diagnostike glaukomy. [Annals of Ophthalmology]. Vestnik oftal’mologii. 2001; 117 (6): 38-39. (in Russ.).