Received: 27 November  2018; Published: 28 February 2019 

Comprehensive treatment of patients with refractory glaucoma complicated by bullous keratopathy

O.V. Guzun, Cand. Med. Sc.; G.I. Drozhzhyna, Prof., Dr. Med. Sc.

SI “Filatov Institute of Eye Diseases and Tissue Therapy of NAMS of Ukraine” Odessa (Ukraine) 

E-mail: olga.v.guzun@gmail.com

Introduction. Patients with refractory glaucoma complicated by bullous keratopathy often suffer from insupportable pain and uncomfortable sensations in the eye, and visual acuity loss, which worsens the patients’ quality of life.   

Purpose. To study the efficacy of a complex treatment of patients with refractory glaucoma complicated by bullous keratopathy through transscleral cyclophotocoagulation (TS CPC ) (λ=1.06 µm) followed by laser stimulation for corneal regeneration (λ=0.63 µm) and in combination with a preservative-free tear substitute bio-protector, containing 3% trehalose and 0.15% sodium hyaluronate.  

Material and Methods. 23 patients (23 eyes) with refractory glaucoma complicated by bullous keratopathy were treated. TS CPC was performed using neodymium laser (λ=1.06 µm; 3 sessions). On completion of a TS CPC course, each patient underwent a course of helium-neon laser stimulation of the cornea (λ=0.63 µm, t=300 sec, 10 sessions) and a 3-month course of a bio-protective tear substitute, containing 3% trehalose and 0.15% sodium hyaluronate (1 drop thrice a day). 

Each patient underwent visual acuity assessment, IOP measurement, Ocular Surface Disease Index (OSDI) evaluation before treatment, after a course of TCCSC, and after a three-month follow-up.  

Results. The TS CPC course resulted in pain management in all patients. The post-treatment IOP level decreased to 26.0 mmHg, by 30%, as compared to pre-treatment IOP level and remained stable at 3 months. Visual acuity improved in 10 of 23 patients (43%). Dry eye severity decreased by 34% (OSDI=59.4 scores). 

Conclusions. The patients with refractory glaucoma complicated by bullous keratopathy had a significantly decreased IOP level (by 30% in 65% of the patients) after a TS CPC course. The following laser stimulation of the cornea in combination with a course of preservative-free tear substitute, containing 3% trehalose and 0.15% sodium hyaluronate, decreased the severity of dry eye disease and corneal syndrome by 34% and significantly improved the patients’ quality of life.  

Keywords: refractory glaucoma, bullous keratopathy, transscleral laser cyclophotocoagulation, laser stimulation of the cornea, a substitute-bioprotector,   3% trehalose, 0.15% sodium hyaluronate.


  1. Boiko EV, Shishkin MM, Gudakovskii YuP, Yan AV. [On the treatment of endothelial-epithelial dystrophy of the cornea by the method of pancorneal photocoagulation using a ytterbium-erbium laser]. Oftalmokhirurgiia. 2002;2:3-7. (In Russian).  
  2. Chechin PP, Guzun OV, Khramenko NI, Peretyagin OA. Efficacy of transscleral Nd:YAG laser cyclophotocoagulation and changes in blood circulation in the eye of patients with absolute glaucoma. J.ophthalmol.(Ukraine).2018;2:34-39.
  3. Bloom PA, Clement CI, King A, Noureddin B, Sharma K, Hitchings RA, Khaw PT. A comparison between tube surgery, ND:YAG laser and diode laser cyclophotocoagulation in the management of refractory glaucoma.  Biomed Res Int. 2013. – 371951. Published online 2013 Oct 7. doi:  10.1155/2013/371951
  4. Chen MJ,  Liu CJ,  Cheng CY,  Lee SM. Corneal status in primary angle-closure glaucoma with a history of acute attack. J Glaucoma. 2012; Jan 21(1):12-6. doi: 10.1097/IJG.0b013e3181fc800a.
  5. Cursiefen C, Kuchle M, Naumann GO. Changing indications for penetrating keratoplasty: histopathology of 1,250 corneal buttons. Cornea.1998;17:468–70. 
  6. Eguchi H, Hiura A,  Nakagawa H, Kusaka S, Shimomura Y. Corneal Nerve Fiber Structure, Its Role in Corneal Function, and Its Changes in Corneal Diseases. Biomed Res Int. 2017. 3242649.
  7. Filippova ЕО, Sokhoreva VV, Pichugin VF. Study the possibility of using nuclear track membranes for ophthalmology. Membranes and membrane technology. 2014;4(4): 1. 
  8. Frezzott P, Mittica V, Martone G, Motolese I, Lomurno L, Peruzzi S, Motolese E. Longterm follow-up of diode laser transscleral cyclophotocoagulation in the treatment of refractory glaucoma. Acta ophthalmologica. 2010;88:150-155.
  9. Galor A,  Moein HR,  Lee C,  Rodriguez A, Felix ER,  Sarantopoulos KD,  Levitt RC. Neuropathic pain and dry eye. Ocul Surf. 2018;16(1):31-44.
  10. Hamblin MR. Mechanisms and Mitochondrial Redox Signaling in Photobiomodulation. Photochem Photobiol. 2017. Nov 22. doi: 10.1111/php.12864. 
  11. Jones LT. The lacrimal secretory system and its treatment. Ophthalmol. 1966. 62(1):47-60. 
  12. Zadorozhnyy O, Korol A, Nevska A, Kustryn T, Pasyechnikova N. Сiliary body imaging with transpalpebral near-infrared transillumination (Pilot study). Klinika oczna. 2016;3:184-6.
  13. Zadorozhnyy OS, Guzun OV, Bratishko AIu et al. Infrared thermography of external ocular surface in patients with absolute glaucoma in transscleral cyclophotocoagulation: a pilot study. J. ophthalmol. (Ukraine). 2018;2:23-8.
  14. Kaleem M,  Ridha F,  Shwani Z,  Swenor B,  Goshe J,  Singh A. Rates of Intraocular Pressure Elevation and Use of Topical Antihypertensive Medication After Descemet Stripping Automated Endothelial Keratoplasty. Cornea. 2017;36(6):669-74.
  15. Kheirkhah A,  Dohlman TH, Amparo  F,  Arnoldner MA, Jamali  A,  Hamrah P,  Dana R. Effects of corneal nerve density on the response to treatment in dry eye disease. Ophthalmology. 2015;122:662–8. 
  16. Li X, Zhang Z, Ye L, Meng J, Zhao Z, Liu Z, Hu J. Acute ocular hypertension disrupts barrier integrity and pump function in rat corneal endothelial cells. Sci Rep. 2017; Jul 31; 7(1):6951.
  17. Melamed S, Ben-Sira I, Ben-Shaul Y. Ultrastructure of fenestrations in endothelial choriocapillaries of the rabbit – a freeze-fracturing study. The British journal of ophthalmology. 1980;64:537-43. 
  18. Ndulue JK, Rahmatnejad К,  Sanvicente С,  Wizov SS,  Moster  MR. Evolution of Cyclophotocoagulation. J Ophthalmic Vis Res. 2018;13 (1):55-61.
  19. Pajoohesh-Ganji A, Pal-Ghosh S,  Tadvalkar G,  Kyne BM,  Saban DR,  Steppet MA al. Partial denervation of sub-basal axons persists following debridement wounds to the mouse cornea. Lab Invest. 2015;95:1305–18.
  20. Pedersen IB,  Ivarsen А, Hjortdal  J. Graft rejection and failure following endothelial keratoplasty (DSAEK) and penetrating keratoplasty for secondary endothelial failure. Acta Ophthalmol. 2015;93(2):172-7.
  21. Raivio VE,  Vesaluoma MH,  Tervo TM,  Immonen IJ,  Puska PM. Corneal innervation, corneal mechanical sensitivity, and tear fluid secretion after transscleral contact 670-nm diode laser cyclophotocoagulation. J Glaucoma. 2002;11(5):46-453.
  22. Rowsey TG, Karamichos D. A role of lipids is in the diseases of cornea and dystrophy : systematic review. Clin Transl Med. 2017;6:30. 
  23. Saini M, Vanathi M, Dada T, Agarwal T, Dhiman R,   Khokhar S. Ocular surface evaluation in eyes with chronic glaucoma on long term topical antiglaucoma therapy. Int J Ophthalmol. 2017;10(6):931–8.
  24. Salehpour F, Mahmoudi J,  Kamari F, Sadigh-Eteghad S,  Rasta SH,  Hamblin MR. Brain Photobiomodulation Therapy: a Narrative Review /F. Salehpour,  // Mol Neurobiol. 2018; Jan 11. doi: 10.1007/s12035-017-0852-4. [Epub ahead of print]
  25. Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000;118: 615-21. 
  26. Tham CC, Kwong YY,  Lai JS,  Lam DS. Effect of a previous acute angle closure attack on the corneal endothelial cell density in chronic angle closure glaucoma patients. J Glaucoma. 2006; Dec 15(6):482-5.
  27. Yüksel N, Emre E, Pirhan D. Evaluation of Corneal Microstructure in Pseudoexfoliation Syndrome and Glaucoma: In Vivo Scanning Laser Confocal Microscopic Study. Curr Eye Res. 2016;41(1):34-40.