Received: 25 May 2018; Published  on-line: 31 August 2018

Clinical efficacy of treatment for subclinical-stage axial diabetic optic neuropathy

M.A. Karliychuk,1 Cand Sc (Med), P.A. Bezditko,2 Dr Sc (Med), Prof.

1 Higher State Educational Establishment of Ukraine «Bukovinian State Medical University»;  Chernivtsi (Ukraine)

2 Kharkiv National Medical University; Kharkiv (Ukraine)

E-mail: mari13karli@gmail.com              

Background: There is no standard of therapy for the treatment of diabetic optic neuropathy (DON).

Purpose: To assess the clinical efficacy of thioctic acid, topical brimonidine tartrate and a combination of vitamins В1, В6, and В12 in the management of subclinical-stage axial DON.

Materials and Methods: Forty patients (63 eyes) were followed up after being diagnosed with subclinical-stage axial DON. The adjunct group was composed of 20 patients (32 eyes) who were administered (1) thioctic acid (Berlithion) at a dose of one 300 mg tablet a day for 42 days, (2) a 2 ml intramuscular injection of Milgamma, once per 3 days for 21 days, followed by switching to oral regimen,  1 tablet per  3 days for 21 days in two courses during a year, and (3) topical brimonidine tartrate 0.2%, 1-2 drops twice a day on a constant basis, as adjunctive to hypoglycemic therapy. The control group (20 patients; 31 eyes) received hypoglycemic therapy only. In addition to routine eye examination, retinal and optic nerve optical coherence tomography and electrophysiology were performed. Patients underwent an examination at baseline, 1.5 months, 6 months, 7.5 months, 13.5 months, 24 months and 25.5 months after treatment.

Results: No progression of optic nerve damage was found in all 32 affected eyes of the adjunct group versus no progression, progression to mild-stage axial DON, and progression to advanced-stage axial DON in 64.5% (20 eyes), 35.5% (11 eyes) and 6.5% (2 eyes), respectively, of the controls at the 25.5-month time point. We found that our treatment attenuated the progression of optic nerve damage in subclinical-stage axial DON, with 25.9% better visual acuity, 29.5 % lower electrically evoked phosphene thresholds, 69.3% less ganglion cell complex (GCC) focal loss volume (FLV), and 29.8% less thickness of the cribriform plate compared to controls at 25.5 months.

Conclusion: Our treatment was found to be clinically efficacious in attenuating the progression of optic nerve damage in subclinical-stage axial DON.

Keywords: axial diabetic optic neuropathy, subclinical stage, treatment, efficacy


  1. Ametov AS, Chernikova NA. [Current aspects of treatment of diabetic polyneuropathy in patients with diabetes mellitus]. Meditsinskii sovet. 2016;8:54–7. Russian
  2. Bakulin IS, Zakharova MN. [Lipoic acid in a pathogenetic therapy for diabetic polyneuropathy]. Nervnye bolezni. 2017;2:3–9. Russian
  3. Likhachev SA, Khodulev VI, Vasilevskaya LA, et al. [Diabetic polyneuropathy: Current aspects of diagnosis and treatment]. Nevrologiia i khirurgiia. Vostochnaia Evropa. 2017;3:155–67. Russian
  4. Morgunov LY. [Alpha-lipoic acid drugs in the treatment of diabetic neuropathy].   Meditsinskii sovet. 2014;17:90–4. Russian
  5. Jayabalan B, Low LL. Vitamin B supplementation for diabetic peripheral neuropathy. Singapore Med J. 2016 Feb; 57(2):55-9.
    Crossref   Pubmed
  6. Strokov IA, Fokina AS. [Novel potential for the treatment of diabetic complications]. RMZh.  2012;20:88–91. Russian
  7. Javed S, Alam U, Malik RA. Treating Diabetic Neuropathy: Present Strategies and Emerging Solutions. Rev Diabet Stud. 2015 Spring-Summer;12(1-2):63-83.
    Crossref   Pubmed
  8. Stracke H, Lindemann A, Federlin K. A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy. Exp Clin Endocrinol Diabetes. 1996;104(4):311–6.
    Crossref   Pubmed
  9. Bolton WK, Cattran DC, Williams ME, Adler SG, Appel GB, et al. Randomized trial of an inhibitor of formation of advanced glycation end products in diabetic nephropathy. Am J Nephrol. 2004;24(1):32–40.
    Crossref   Pubmed
  10. Edwards JL, Vincent А, Cheng T, Feldman EL. Diabetic Neuropathy: Mechanisms to Management. Pharmacol Ther. 2008;120(1):1-34.
    Crossref   Pubmed
  11. Simo R, Hernandez C; European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR). Neurodegeneration in the diabetic eye: new insights and therapeutic perspectives. Trends Endocrinol Metab. 2014 Jan;25(1):23-33.
    Crossref   Pubmed
  12. Karliychuk MA. [Diagnostic criteria of subclinical-stage diabetic optic neuropathy]. Bukovinian Medical Herald. 2017; 21(3):29–35. Ukrainian
  13. Bezditko PA, Karliychuk MA. [Clinical-diagnostic criteria of different types of nerve damage in patients with diabetes mellitus]. Arkhiv oftalmologii Ukrainy. 2017;5(3):18–22. Ukrainian
  14. Bezditko PA, Karliychuk MA, Lukhanin OO, Zavoloka OV. [Use of spectral optical coherence tomography for studying thickness of the cribriform plate and scleral canal area]. Kharkivska khirurgichna shkola. 2017; 3–4:63–9. Ukrainian
  15. Zhaboiedov GD, Skrypnyk RL, Sidorova MV. Patent 43079 А of Ukraine А 61 F 9/00. [Method for treatment of diabetic polyneuropathy ]. Patent application dated 09.02.2001. Official Bulletin "Promyslova Vlasnist".  2001; 10:4–28. Ukrainian
  16. Amano S, Kaji Y, Oshika T, Oka T, Machinami R, et al. Advanced glycation end products in human optic nerve head. Br J Ophthalmol. 2001 Jan;85(1):52–5.
    Crossref   Pubmed
  17. Spoerl E, Boehm AG, Pillunat LE. The influence of various substances on the biomechanical behavior of lamina cribrosa and peripapillary sclera. Invest Ophthalmol Vis Sci. 2005; 46(4):1286–90.
    Crossref   Pubmed
  18. Terai N, Spoerl E, Haustein M, et al. Diabetes mellitus affects biomechanical properties of the optic nerve head in the rat. Ophthalmic Res. 2012;47(4):189–94
    Crossref   Pubmed
  19. Lee EJ, Kim TW, Kim M, Kim H. Influence of lamina cribrosa thickness and depth on the rate of progressive retinal nerve fiber layer thinning. Ophthalmology. 2015;122:721–9.
    Crossref   Pubmed
  20. Saylor M, McLoon LK, Harrison AR, Lee MS. Experimental and clinical evidence for brimonidine as an optic nerve and retinal neuroprotective agent: an evidence-based review. Arch Ophthalmol. 2009 Apr;127(4):402-6.
    Crossref   Pubmed