Neovascular Glaucoma: An Update

Abstract

Neovascular glaucoma (NVG) is a severe type of secondary glaucoma with devastating complications and generally poor visual prognosis. NVG is defined by the development of pathological neovessels over the iris and the iridocorneal angle that can block the outflow of aqueous humor, causing elevation of intraocular pressure (IOP). The pathogenesis of NVG is, in most cases, associated with ischemia of the posterior segment, which is most frequently associated with proliferative diabetic retinopathy or central retinal vein occlusion. The advanced stages of NVG are by iris and angle neovascularization, angle, and extremely high IOP, accompanied by ocular pain and poor vision. The therapeutic approach of NVG is based on the reduction of retinal ischemia by panretinal photocoagulation. Intravitreal anti-VEGF administration can contribute to the regression of neovascularization, and topical and systemic medications may be necessary for IOP control. However, if medical treatment with these agents is not enough, surgical procedures may be required to lower IOP and prevent glaucomatous optic neuropathy. Early and prompt diagnosis, with identification of the underlying etiology, can improve IOP control and final visual outcome. The aim of this study is to review current knowledge of the pathogenesis and management of NVG.

Zusammenfassung

Das neovaskuläre Glaukom (NVG) ist eine schwere Form des sekundären Glaukoms mit verheerenden Komplikationen und allgemein schlechter Prognose für das Sehvermögen. Das NVG ist definiert durch die Entwicklung pathologischer Gefäßneubildungen über der Iris und dem Iridokornealwinkel, die den Abfluss des Kammerwassers blockieren und eine Erhöhung des Augendrucks verursachen können. Die Pathogenese der NVG ist in den meisten Fällen mit einer Ischämie des hinteren Segments verbunden, verursacht ist durch proliferative diabetische Retinopathie oder Zentralvenenverschluss. Die fortgeschrittenen Stadien der NVG sind gekennzeichnet durch Iris- und Kammerwinkelneovaskularisation und -verschluss und extrem hohen Augendruck, begleitet von Augenschmerzen und Sehstörungen. Der therapeutische Ansatz von NVG basiert auf der Reduktion der retinalen Ischämie durch panretinale Photokoagulation. Die intravitreale Verabreichung von Anti-VEGF kann zur Regression der Neovaskularisation beitragen, und topische und systemische Antiglaukommedikamente können für die Augendruckkontrolle erforderlich sein. Wenn jedoch eine medizinische Behandlung mit diesen Mitteln nicht ausreicht, können chirurgische Eingriffe erforderlich sein, um den Augendruck zu senken und einer glaukomatösen Optikusneuropathie vorzubeugen. Eine frühzeitige und schnelle Diagnose mit Identifizierung der zugrunde liegenden Ätiologie kann die Augendruckkontrolle und das endgültige Sehergebnis verbessern. Das Ziel dieser Studie ist es, den aktuellen Wissensstand über die Pathogenese und das Management von NVG zu überprüfen.

Key words

neovascular glaucoma - panretinal photocoagulation - anti-VEGF - glaucoma surgery - diode laser

Schlüsselwörter

neovaskuläres Glaukom - panretinale Photokoagulation - Anti-VEGF - Glaukomchirurgie - Diodenlaser

Publication History

Received: 18 August 2022

Accepted: 27 September 2022

Article published online:
27 November 2022

• References

• 1 Coats G. Further cases of thrombosis of the central vein. Roy Lond Ophthal Hosp Rep 1906; 16: 516
• 2 Albert DM, Jakobiec FA. Neovascular Glaucoma. In: Albert DM, Jakobiec FA. eds. Principles and Practice of Ophthalmology. Philadelphia: WB Saunders Publishers; 1999
• 3 Salus R. Rubeosis iridis diabetica, eine bisher unbekannte diabetische Irisveränderung. Med Klin 1928; 24: 256
• 4 Weiss DI, Shaffer RN, Nehrenberg TR. Neovascular glaucoma complicating carotid-cavernous sinus fistula. Arch Ophthalmol 1963; 69: 304-307 DOI: 10.1001/archopht.1963.00960040310007.
• 5 Fiore C, Lupidi G, Santoni G. [Retrobulbar injection of chlorpromazine in the absolute glaucoma]. J Fr Ophtalmol 1980; 3: 397-399
• 6 Sivak-Callcott JA, OʼDay DM, Gass JD. et al. Evidence-based recommendations for the diagnosis and treatment of neovascular glaucoma. Ophthalmology 2001; 108: 1767-1800 DOI: 10.1016/s0161-6420(01)00775-8.
• 7 Wand M. Neovascular Glaucoma. In: Ritch RSM, Krupin T. eds. The Glaucomas. Vol. 2. St. Louis: CV Mosby; 1996: 1063-1110
• 8 Mocanu C, Barascu D, Marinescu F. et al. [Neovascular glaucoma – retrospective study]. Oftalmologia 2005; 49: 58-65
• 9 Hayreh SS, Rojas P, Podhajsky P. et al. Ocular neovascularization with retinal vascular occlusion. III. Incidence of ocular neovascularization with retinal vein occlusion. Ophthalmology 1983; 90: 488-506 DOI: 10.1016/s0161-6420(83)34542-5.
• 10 Chen HF, Chen MC, Chuang LH. et al. Neovascular glaucoma after central retinal vein occlusion in pre-existing glaucoma. BMC Ophthalmol 2014; 14: 119 DOI: 10.1186/1471-2415-14-119.
• 11 Fernández-Vigo J, Castro J, Macarro A. Diabetic iris neovascularization. Natural history and treatment. Acta Ophthalmol Scand 1997; 75: 89-93 DOI: 10.1111/j.1600-0420.1997.tb00258.x.
• 12 Lee P, Wang CC, Adamis AP. Ocular neovascularization: an epidemiologic review. Surv Ophthalmol 1998; 43: 245-269 DOI: 10.1016/s0039-6257(98)00035-6.
• 13 Armaly MF, Baloglou PJ. Diabetes mellitus and the eye. 1. Changes in the anterior segment. Arch Ophthalmol 1967; 77: 485-492 DOI: 10.1001/archopht.1967.00980020487011.
• 14 Madsen PH. Haemorrhagic glaucoma. Comparative study in diabetic and nondiabetic patients. Br J Ophthalmol 1971; 55: 444-450 DOI: 10.1136/bjo.55.7.444.
• 15 Nielsen NV. The prevalence of glaucoma and ocular hypertension in type 1 and 2 diabetes mellitus. An epidemiological study of diabetes mellitus on the island of Falster, Denmark. Acta Ophthalmol (Copenh) 1983; 61: 662-672 DOI: 10.1111/j.1755-3768.1983.tb04357.x.
• 16 Ohrt V. The frequency of rubeosis iridis in diabetic patients. Acta Ophthalmol (Copenh) 1971; 49: 301-307 DOI: 10.1111/j.1755-3768.1971.tb00954.x.
• 17 Vasconcellos JP, Costa VP, Kara-Jose N. Neovascular glaucoma: epidemiology and prognostic factors. Proposal of a flow chart to guide the treatment. Arq Bras Oftalmol 1998; 61: 519-524
• 18 Pedroso L, Carvalho Junior ES, Paranhos A. et al. The real cost of glaucoma treatment for an outpatient. Arq Bras Oftalmol 1999; 62: 677-682
• 19 Kahook M, Shuman J. Chandler and Grantʼs Glaucoma. Thorofare: Slack; 2013: 309-317
• 20 Shazly TA, Latina MA. Neovascular glaucoma: etiology, diagnosis and prognosis. Semin Ophthalmol 2009; 24: 113-121 DOI: 10.1080/08820530902800801.
• 21 Gartner S, Henkind P. Neovascularization of the iris (rubeosis iridis). Surv Ophthalmol 1978; 22: 291-312 DOI: 10.1016/0039-6257(78)90175-3.
• 22 Hayreh SS. Neovascular glaucoma. Prog Retin Eye Res 2007; 26: 470-485 DOI: 10.1016/j.preteyeres.2007.06.001.
• 23 John T, Sassani JW, Eagle Jr. RC. The myofibroblastic component of rubeosis iridis. Ophthalmology 1983; 90: 721-728 DOI: 10.1016/s0161-6420(83)34520-6.
• 24 Michelson IC. The mode of development of the vascular system of the retina with some observations on its significance for certain retinal disorders. Trans Ophthalmol Soc U K 1948; 68: 137-180
• 25 Leung DW, Cachianes G, Kuang WJ. et al. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989; 246: 1306-1309 DOI: 10.1126/science.2479986.
• 26 Wang JW, Zhou MW, Zhang X. et al. Short-term effect of intravitreal ranibizumab on intraocular concentrations of vascular endothelial growth factor-A and pigment epithelium-derived factor in neovascular glaucoma. Clin Exp Ophthalmol 2015; 43: 415-421 DOI: 10.1111/ceo.12477.
• 27 Aiello LP, Avery RL, Arrigg PG. et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994; 331: 1480-1487 DOI: 10.1056/NEJM199412013312203.
• 28 Sall JW, Klisovic DD, OʼDorisio MS. et al. Somatostatin inhibits IGF-1 mediated induction of VEGF in human retinal pigment epithelial cells. Exp Eye Res 2004; 79: 465-476 DOI: 10.1016/j.exer.2004.06.007.
• 29 Chalam KV, Brar VS, Murthy RK. Human ciliary epithelium as a source of synthesis and secretion of vascular endothelial growth factor in neovascular glaucoma. JAMA Ophthalmol 2014; 132: 1350-1354 DOI: 10.1001/jamaophthalmol.2014.2356.
• 30 Ruberte J, Ayuso E, Navarro M. et al. Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease. J Clin Invest 2004; 113: 1149-1157 DOI: 10.1172/JCI19478.
• 31 Chen T, Zeng SQ, Lu YY. et al. The change of the level of the vascular endothelial growth factor in aqueous humor of patients with neovascular glaucoma before and after anterior retinal cryotherapy. Zhonghua Yan Ke Za Zhi 2007; 43: 622-625
• 32 Chen KH, Wu CC, Roy S. et al. Increased interleukin-6 in aqueous humor of neovascular glaucoma. Invest Ophthalmol Vis Sci 1999; 40: 2627-2632
• 33 Tripathi RC, Borisuth NS, Tripathi BJ. Detection, quantification, and significance of basic fibroblast growth factor in the aqueous humor of man, cat, dog and pig. Exp Eye Res 1992; 54: 447-454 DOI: 10.1016/0014-4835(92)90056-x.
• 34 Yu XB, Sun XH, Dahan E. et al. Increased levels of transforming growth factor-beta1 and -beta2 in the aqueous humor of patients with neovascular glaucoma. Ophthalmic Surg Lasers Imaging 2007; 38: 6-14 DOI: 10.3928/15428877-20070101-01.
• 35 Iwabe S, Lamas M, Vásquez Pélaez CG. et al. Aqueous humor endothelin-1 (Et-1), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) levels in Mexican glaucomatous patients. Curr Eye Res 2010; 35: 287-294 DOI: 10.3109/02713680903545315.
• 36 Chiou SH, Chang CJ, Chou CK. et al. Increased nitric oxide levels in aqueous humor of diabetic patients with neovascular glaucoma. Diabetes Care 1999; 22: 861-862 DOI: 10.2337/diacare.22.5.861a.
• 37 Oshida E, Arai K, Sakai M. et al. Study of free radicals in aqueous humor in glaucoma and cataracts: differences in presence or absence of diabetes mellitus and neovascular glaucoma. Nihon Ganka Gakkai Zasshi 2014; 118: 759-767
• 38 da Cruz Escaleira ALR, Kalogeropoulos D, Kalogeropoulos C. et al. Four common diseases causing sudden blindness or death in the eye emergency department. Postgrad Med J 2021; 97: 256-263 DOI: 10.1136/postgradmedj-2020-138163.
• 39 Havens SJ, Gulati V. Neovascular Glaucoma. Dev Ophthalmol 2016; 55: 196-204 DOI: 10.1159/000431196.
• 40 Bonnet M, Jourdain M, Francoz-Taillanter N. [Clinical correlation between rubeosis iridis and optic disc neovascularization (authorʼs transl)]. J Fr Ophtalmol 1981; 4: 405-410
• 41 Lanzl IM, Wilson RP, Dudley D. et al. Outcome of trabeculectomy with mitomycin-C in the iridocorneal endothelial syndrome. Ophthalmology 2000; 107: 295-297 DOI: 10.1016/s0161-6420(99)00077-9.
• 42 [Anonymous] Natural history and clinical management of central retinal vein occlusion. The Central Vein Occlusion Study Group. Arch Ophthalmol 1997; 115: 486-491 DOI: 10.1001/archopht.1997.01100150488006.
• 43 Magargal LE, Donoso LA, Sanborn GE. Retinal ischemia and risk of neovascularization following central retinal vein obstruction. Ophthalmology 1982; 89: 1241-1245 DOI: 10.1016/s0161-6420(82)34655-2.
• 44 Hoskins jr. HD. Neovascular glaucoma: current concepts. Trans Am Acad Ophthalmol Otol 1974; 78: 330
• 45 Magargal LE, Brown GC, Augsburger JJ. et al. Neovascular glaucoma following branch retinal vein obstruction. Ophthalmology 1981; 88: 1095-1101 DOI: 10.1016/s0161-6420(81)34901-x.
• 46 Hayreh SS, Podhajsky P. Ocular neovascularization with retinal vascular occlusion. II. Occurrence in central and branch retinal artery occlusion. Arch Ophthalmol 1982; 100: 1585-1596 DOI: 10.1001/archopht.1982.01030040563002.
• 47 Brown GC, Magargal LE, Schachat A. et al. Neovascular glaucoma. Etiologic considerations. Ophthalmology 1984; 91: 315-320 DOI: 10.1016/s0161-6420(84)34293-2.
• 48 Abedin S, Simmons RJ. Neovascular glaucoma in systemic occlusive vascular disease. Ann Ophthalmol 1982; 14: 284-287
• 49 Duker JS, Brown GC. Iris neovascularization associated with obstruction of the central retinal artery. Ophthalmology 1988; 95: 1244-1250 DOI: 10.1016/s0161-6420(88)33042-3.
• 50 Sugar HS. Neovascular glaucoma after carotid-cavernous fistula formation. Ann Ophthalmol 1979; 11: 667
• 51 Brown GC, Magargal LE, Simeone FA. et al. Arterial obstruction and ocular neovascularization. Ophthalmology 1982; 89: 139-146 DOI: 10.1016/s0161-6420(82)34837-x.
• 52 Tanaka S, Ideta H, Yonemoto J. et al. Neovascularization of the iris in rhegmatogenous retina detachment. Am J Ophthalmol 1991; 112: 632-634 DOI: 10.1016/s0002-9394(14)77268-x.
• 53 Wilhelmus KR, Grierson I, Watson PG. Histopathologic and clinical associations of scleritis and glaucoma. Am J Ophthalmol 1981; 91: 697-705 DOI: 10.1016/0002-9394(81)90001-5.
• 54 Yanoff M. Mechanisms of glaucoma in eyes with uveal melanoma. Ophthalmol Clin 1972; 12: 51
• 55 Walton DS, Grant WM. Retinoblastoma and iris neovascularization. Am J Ophthalmol 1968; 65: 598-599 DOI: 10.1016/0002-9394(68)93882-8.
• 56 Lin SA. Ophthalmology: case studies. Ophthalmology 2001; 1: 90-93
• 57 Rodgin SG. Neovascular glaucoma associated with uveitis. J Am Otom Assoc 1987; 58: 499-503
• 58 Centofanti M, Manni GL, Napoli D. et al. Comparative effects of intraocular pressure between systemic and topical carbonic anhydrase inhibitors: a clinical masked, cross-over study. Pharmacol Res 1997; 35: 481-485 DOI: 10.1006/phrs.1997.0167.
• 59 Laatikainen L, Kohner EM, Khoury D. et al. Panretinal photocoagulation in central retinal vein occlusion: a randomised controlled clinical study. Br J Ophthalmol 1977; 61: 741-753 DOI: 10.1136/bjo.61.12.741.
• 60 Murphy RP, Egbert PR. Regression of iris neovascularization following panretinal photocoagulation. Arch Ophthalmol 1979; 97: 700-702 DOI: 10.1001/archopht.1979.01020010352013.
• 61 Lang GE. Laser treatment of diabetic retinopathy. Dev Ophthalmol 2007; 39: 48-68 DOI: 10.1159/000098499.
• 62 Terelak-Borys B, Skonieczna K, Grabska-Liberek I. Ocular ischemic syndrome – a systematic review. Med Sci Monit 2012; 18: RA138-RA144
• 63 Mizener JB, Podhajsky P, Hayreh SS. Ocular ischemic syndrome. Ophthalmology 1997; 104: 859-864 DOI: 10.1016/s0161-6420(97)30221-8.
• 64 Brown GC. Anterior ischemic optic neuropathy occurring in association with carotid artery obstruction. J Clin Neuroophthalmol 1986; 6: 39-42
• 65 Park SC, Su D, Tello C. Anti-VEGF therapy for the treatment of glaucoma: a focus on ranibizumab and bevacizumab. Expert Opin Biol Ther 2012; 12: 1641-1647 DOI: 10.1517/14712598.2012.721772.
• 66 SooHoo JR, Seibold LK, Kahook MY. Recent advances in the management of neovascular glaucoma. Semin Ophthalmol 2013; 28: 165-172 DOI: 10.3109/08820538.2012.730103.
• 67 Horsley MB, Kahook MY. Anti-VEGF therapy for glaucoma. Curr Opin Ophthalmol 2010; 21: 112-117 DOI: 10.1097/ICU.0b013e3283360aad.
• 68 SooHoo JR, Seibold LK, Kahook MY. The link between intravitreal antivascular endothelial growth factor injections and glaucoma. Curr Opin Ophthalmol 2014; 25: 127-133 DOI: 10.1097/ICU.0000000000000036.
• 69 Schlote T, Derse M, Rassmann K. et al. Efficacy and safety of contact transscleral diode laser cyclophotocoagulation for advanced glaucoma. J Glaucoma 2001; 10: 294-301 DOI: 10.1097/00061198-200108000-00009.
• 70 Murphy CC, Burnett CA, Spry PG. et al. A two centre study of the dose-response relation for transscleral diode laser cyclophotocoagulation in refractory glaucoma. Br J Ophthalmol 2003; 87: 1252-1257 DOI: 10.1136/bjo.87.10.1252.
• 71 Ramli N, Htoon HM, Ho CL. et al. Risk factors for hypotony after transscleral diode cyclophotocoagulation. J Glaucoma 2012; 21: 169-173 DOI: 10.1097/IJG.0b013e318207091a.
• 72 Lima FE, Magacho L, Carvalho DM. et al. A prospective, comparative study between endoscopic cyclophotocoagulation and the Ahmed drainage implant in refractory glaucoma. J Glaucoma 2004; 13: 233-237 DOI: 10.1097/00061198-200406000-00011.
• 73 Allen RC, Bellows AR, Hutchinson BT. et al. Filtration surgery in the treatment of neovascular glaucoma. Ophthalmology 1982; 89: 1181-1187 DOI: 10.1016/s0161-6420(82)34672-2.
• 74 Mietz H, Raschka B, Krieglstein GK. Risk factors for failures of trabeculectomies performed without antimetabolites. Br J Ophthalmol 1999; 83: 814-821 DOI: 10.1136/bjo.83.7.814.
• 75 Sisto D, Vetrugno M, Trabucco T. et al. The role of antimetabolites in filtration surgery for neovascular glaucoma: intermediate-term follow-up. Acta Ophthalmol Scand 2007; 85: 267-271 DOI: 10.1111/j.1600-0420.2006.00810.x.
• 76 Nakatake S, Yoshida S, Nakao S. et al. Hyphema is a risk factor for failure of trabeculectomy in neovascular glaucoma: a retrospective analysis. BMC Ophthalmol 2014; 26: 14-55 DOI: 10.1186/1471-2415-14-55.
• 77 Yalvac IS, Eksioglu U, Satana B. et al. Long-term results of Ahmed glaucoma valve and Molteno implant in neovascular glaucoma. Eye (Lond) 2007; 21: 65-70 DOI: 10.1038/sj.eye.6702125.
• 78 Hernandez-Oteyza A, Lazcano-Gomez G, Jimenez-Roman J. et al. Surgical outcome of Ahmed valve implantation in Mexican patients with neovascular glaucoma. J Curr Glaucoma Pract 2014; 8: 86-90 DOI: 10.5005/jp-journals-10008-1168.
• 79 Netland PA, Ishida K, Boyle JW. The Ahmed Glaucoma Valve in patients with and without neovascular glaucoma. J Glaucoma 2010; 19: 581-586 DOI: 10.1097/IJG.0b013e3181ca7f7f.
• 80 Every SG, Molteno AC, Bevin TH. et al. Long-term results of Molteno implant insertion in cases of neovascular glaucoma. Arch Ophthalmol 2006; 124: 355-360 DOI: 10.1001/archopht.124.3.355.
• 81 Shen CC, Salim S, Du H. et al. Trabeculectomy versus Ahmed Glaucoma Valve implantation in neovascular glaucoma. Clin Ophthalmol 2011; 5: 281-286 DOI: 10.2147/OPTH.S16976.
• 82 Cheng Y, Liu XH, Shen X. et al. Ahmed valve implantation for neovascular glaucoma after 23-gauge vitrectomy in eyes with proliferative diabetic retinopathy. Int J Ophthalmol 2013; 6: 316-320 DOI: 10.3980/j.issn.2222-3959.2013.03.11.
• 83 Park UC, Park KH, Kim DM. et al. Ahmed glaucoma valve implantation for neovascular glaucoma after vitrectomy for proliferative diabetic retinopathy. J Glaucoma 2011; 20: 433-438 DOI: 10.1097/IJG.0b013e3181f3eb06.
• 84 Salman AG. Intrasilicone bevacizumab injection for iris neovascularization after vitrectomy for proliferative diabetic retinopathy. Ophthalmic Res 2013; 49: 20-24 DOI: 10.1159/000341734.
• 85 Wallsh JO, Gallemore RP, Taban M. et al. Pars plana Ahmed valve and vitrectomy in patients with glaucoma associated with posterior segment disease. Retina 2013; 33: 2059-2068 DOI: 10.1097/IAE.0b013e31828992c3.
• 86 Kolomeyer AM, Seery CW, Emami-Naemi P. et al. Combined pars plana vitrectomy and pars plana Baerveldt tube placement in eyes with neovascular glaucoma. Retina 2015; 35: 17-28 DOI: 10.1097/IAE.0000000000000235.
• 87 Gil-Carrasco F, Jiménez-Román J, Turati-Acosta M. et al. Comparative study of the safety and efficacy of the Ahmed glaucoma valve model M4 (high density porous polyethylene) and the model S2 (polypropylene) in patients with neovascular glaucoma. Arch Soc Esp Oftalmol 2016; 91: 409-414 DOI: 10.1016/j.oftal.2016.02.009.
• 88 Guven YS, Yildirim S, Degirmenci C. et al. Evaluation of Ex-PRESS mini glaucoma shunt implantation with preoperative intracameral bevacizumab injection in refractory neovascular glaucoma. Eur J Ophthalmol 2016; 26: 575-580 DOI: 10.5301/ejo.5000763.
• 89 Nadal J, Carreras E, Kudsieh B. et al. Neovascular glaucoma treatment with extraction of anterior chamber fibrovascular tissue. JAMA Ophthalmol 2013; 131: 1083-1085 DOI: 10.1001/jamaophthalmol.2013.426.
• 90 Vinod K, Gedde SJ. Safety profile of minimally invasive glaucoma surgery. Curr Opin Ophthalmol 2021; 32: 160-168 DOI: 10.1097/ICU.0000000000000731.
• 91 Scheres LMJ, Kujovic-Aleksov S, Ramdas WD. et al. XEN^® Gel Stent compared to PRESERFLO^™ MicroShunt implantation for primary open-angle glaucoma: two-year results. Acta Ophthalmol 2021; 99: e433-e440 DOI: 10.1111/aos.14602.
• 92 Do AT, Parikh H, Panarelli JF. Subconjunctival microinvasive glaucoma surgeries: an update on the Xen gel stent and the PreserFlo MicroShunt. Curr Opin Ophthalmol 2020; 31: 132-138 DOI: 10.1097/ICU.0000000000000643.