Manik Goel, MD and Joel S. Schuman, MD, FACS

Neovascular glaucoma (NVG), a form of secondary angle closure glaucoma, is characterized by the development of new vessels in the anterior segment, namely the iris and anterior chamber angle. The inciting event for new vessel formation and NVG is believed to be retinal hypoxia of any cause. The growth of new vessels leads to the formation of fibrovascular membranes across the anterior chamber angle and subsequently synechial angle closure and elevated intraocular pressure (IOP). NVG can be refractory to treatment and optimal control of IOP is often difficult. The lack of adequate IOP control puts the patient at risk of rapid and severe vision loss; thus, timely recognition and treatment of NVG is critical in preserving useful vision for the patient. Many different treatment modalities have been used in IOP management, including topical and oral hypotensives, cyclophotocoagulation, and filtering surgery. Recently, with the recognition of the role of angiopoietic factors like vascular endothelial growth factor (VEGF) in the pathogenesis of NVG, anti-VEGF agents are being used to achieve better outcomes.

Epidemiology and Pathogenesis

Angiogenesis is the formation of new blood vessels from existing blood vessels. The process of angiogenesis has an important physiologic role in growth, reproduction, and repair after injury.¹ Aberrant angiogenesis plays a critical part in pathological conditions both systemic, like tumor growth and metastases,^2,3 and pertaining to the eye, like diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity.^4–6 VEGF is involved both in physiologic and aberrant angiogenesis;^2–6 hypoxic tissues upregulate VEGF transcription to promote new vessel formation and maintain an adequate supply of essential nutrients.^7,8 As intravitreal administration of anti-VEGF agents have been highly successful in treating ocular neovascular disorders like proliferative diabetic retinopathy and neovacular age-related macular degeneration, they are also being used with good results in the treatment of neovascular glaucoma.

Coats provided the first description of iris neovascularization (NVI) in 1906 in patients with central retinal vein occlusion.9 Weiss et al¹⁰ later coined the term neovascular glaucoma. The primary factor responsible for NVI and the development of NVG is retinal hypoxia (97% of cases). The other 3% is secondary to intraocular inflammation without associated retinal ischemia.¹¹ The 3 most common causes of NVG are central retinal vein occlusion (36%), proliferative diabetic retinopathy (32%), and ocular ischemic syndrome (13%) (Table 15-1).¹¹ In these patients, hypoxia or ischemia induces increased expression of proangiogenic factors like VEGF from the retina.¹² VEGF then diffuses into the anterior segment, causing neovascularization of the iris and angle. This rate is increased in patients after removal of the crystalline lens and even more in those without an intact posterior capsule.^13–15 Elevated levels of VEGF have been detected in the aqueous humor and vitreous of patients with NVG.^16,17 It is reported to be 40 and 113 times higher than that of primary open-angle glaucoma and cataract patients, respectively.^12,16

Many chemokines, other than VEGF, have also been suspected to play a part in angiogenesis. These substances include insulin-like growth factors I and II,¹⁸ platelet-derived growth factor,¹⁹ and basic fibroblast growth factor.¹³ Inflammatory mediators such as angiopoietin 1 and 2 also play a role in new vessel formation.²⁰ At present, the evidence for the role of these other mediators is not as strongly established as for VEGF. However, with more research, the pathway for ocular angiogenesis is being elucidated in more detail and the role of other factors will become more obvious. This may lead to the development of new, more-effective therapeutic agents to target the angiogenic cascade.

Ocular Manifestations and Diagnosis

It is critical to identify and diagnose NVG at the earliest stage to give the patient the best chance at preserving vision. The clinician must have a high index of suspicion in any patient presenting with high IOP and risk factors as outlined in Table 15-1.

NVG is a clinical diagnosis. It is important to obtain a detailed history (including systemic risk factors and history of recent surgeries). A thorough slit lamp examination is warranted in any patient at risk for developing NVG. It is helpful to start with a nondilated pupil to identify new vessels at the pupil margin and perform gonioscopy. However, the importance of performing a dilated posterior segment exam to look for signs of retinal ischemia cannot be overemphasized.

Neovascularization of the anterior segment usually starts with fine vascular tufts at the pupillary margin that then extend radially across the iris surface toward the angle. As the vessels continue to proliferate, they grow across the angle recess extending from the root of the iris to the ciliary body band, scleral spur, and trabecular meshwork. This imparts the characteristic reddish hue to the angle seen in patients with NVG. Although initially the angle may appear open on gonioscopy, the growth of this fibrovascular membrane across the angle impedes aqueous outflow and IOP begins to rise. Eventually, myofibroblasts in the fibrovascular membrane contract causing contracture of the membrane and synechial angle closure.²¹ Corneal endothelial proliferation may also occur across the angle recess.²² At this point, patients may present with severe pain, markedly elevated IOP, and loss of vision. In addition, anterior chamber examination may reveal cells and flare with or without hyphema or ectropion uveae from radial traction on the iris pulling the posterior pigmented epithelial layer of the iris anteriorly. Aqueous humor dynamics²³ dictates that neovascularization makes its first appearance at the pupillary margin; however, NVG may occur without NVI in 6% to 12% of cases of central retinal vein occlusion.24–26

Studying pupillary reactions can help predict the development of rubeosis. Research has shown that patients with central retinal vein occlusion with a relative afferent pupillary defect ≥ 0.6 log units have high sensitivity and specificity in predicting the development of rubeosis.27 Although NVG is a clinical diagnosis, ancillary investigative modalities like angiography and electroretinography can be helpful in detecting subclinical cases.12,28 Iris fluorescein angiography is able to detect NVI in 97% of eyes and in 36% of eyes before being clinically evident.²⁹ Fluorescein angiography of the angle with the Goldmann gonioscopy lens (fluorescein gonioangiography) may be useful in the diagnosis and management of NVG,³⁰ allowing clinicians to follow vascularization both before and after treatment of retinal ischemia. Electroretinography has been proposed as a surrogate marker to assess retinal ischemia and predict the likelihood of developing rubeosis in patients with central retinal vein occlusion.³¹ However, there is a lack of consensus on what electroretinogram parameter (30 Hz implicit time, R_max, b/a wave ratio) is the best predictor for retinal ischemia.^31,32 In one study, the average b/a wave ratio in cases in which NVG developed was 0.84 and greater than 1 when this complication did not develop.³¹ The use of iris angiography, gonioangiography, and electroretinogram may be helpful in predicting, and early detection, of rubeosis but their role needs to be validated further in controlled studies before they can be recommended for routine use in these patients.

Treatment

To ensure a successful outcome and to preserve maximal vision, it is crucial to identify NVG and institute treatment early on. Timely intervention can prevent synechial angle closure and a blind painful eye. Treatment of NVG has 2 critical aims: first, the underlying disease process driving the angiogenic cascade and second, controlling the intraocular pressure.¹²

Ischemic retina is responsible for producing pro-angiogenic factors like VEGF in the vast majority of NVG cases. Primary treatment of rubeosis is thus directed at the retina. Panretinal photocoagulation (PRP) is the current gold-standard treatment for almost all NVG patients and is recommended at the earliest sign of rubeosis. PRP reduces the stimulus for VEGF production by destroying the ischemic retina responsible for VEGF production.^33,34 It leads to the reduction of VEGF levels,³⁵ regression of new vessels in both the anterior and posterior segments,^30,36 and normalization of IOP in up to 42% of patients.³⁰ The improvement in IOP is more likely true for patients who have not yet suffered from angle closure due to fibrovascular membrane formation. PRP also improves the success rate of subsequent filtering surgeries.³⁷

In patients with cloudy media or poor visualization of the retina, panretinal cryotherapy or transscleral diode laser photocoagulation may be performed. Panretinal cryotherapy has been shown to be equally effective as laser in controlling rubeosis.³⁸ It also leads to relief of pain and regression of anterior chamber inflammation in 93.5% of patients.³⁹ Some authors recommend anterior retinal cryotherapy in eyes with media opacities as a preliminary procedure for filtering surgery in eyes with NVG. Other studies have reported similar success with panretinal cryotherapy.^40,41 Another methodology, transscleral diode laser photocoagulation, also ablates peripheral retina and can be used in eyes with poor visualization preventing PRP. Reports in the literature show control and regression of rubeosis with diode laser photocoagulation.^42,43

Although retinal ablative procedures are crucial in eliminating the source of vasoproliferative factors, these treatments lead to death of retinal cells and cause permanent visual field defects.⁴⁴ Treatment with anti-VEGF agents, however, can both regress neovascularization and preserve retinal function. Furthermore, it can be performed in eyes with no view to the posterior segment. Its use in the management of NVG is early, although encouraging. Bevacizumab has been used most commonly and is given intravitreally in the same dose as used to treat diseases of the posterior segment.

PRP and other retinal ablative procedures cause regression of new vessels in the angle and help control IOP. However, most patients will need additional medical or surgical treatment to provide adequate control. Pharmacotherapy with beta-blockers, alpha agonists, and carbonic anhydrase inhibitors is used to further decrease IOP. Prostaglandin analogs may also be used, but their efficacy can be limited because of decreased access of the aqueous to the uveoscleral pathway.12 Miotics are best avoided because of the risk of enticing intraocular inflammation in eyes with an already compromised blood aqueous barrier. In addition, miotics may worsen synechial angle closure and thus IOP control. Other topical treatments include topical steroids to help improve intraocular inflammation and cycloplegic drops to increase uveoscleral outflow. Both steroids and cyclopegics may also help with improving patient comfort.

In a significant percentage of patients, medical therapy alone will not provide adequate long-term IOP control. In these patients, additional intervention is needed and the choice of treatment may be guided by the visual potential of the patient. Patients with useful visual potential are usually treated with glaucoma-filtering surgeries (trabeculectomy or glaucoma drainage implant surgery); patients with poor visual potential often undergo cyclodestructive procedures.

Trabeculectomy or glaucoma drainage implant surgery in patients with NVG should be preceded by PRP to improve success rates. In general, trabeculectomies have a poorer success rate in NVG. Attempts have been made to improve outcomes with use of antimetabolites such as 5-fluorouracil and mitomycin-C (MMC).^45,46 However, the long-term outcomes still remain poor. One reason for this is hemorrhage at the time of surgery and/or in the postoperative period.^45,47 Judicious use of cautery during the surgery to achieve hemostasis is recommended, and some authors advise direct cauterization of the peripheral iris before performing iridectomy. Other risk factors associated with a poor surgical outcome after trabeculectomy include younger age, prior pars plana vitrectomy, type 1 diabetes, and extensive peripheral anterior synechiae.^45,47,48 The success rate 2 to 3 years after trabeculectomy with MMC in NVG patients is reported to be 61%.⁴⁷

As our understanding of the pathophysiology of NVG has improved and the role of VEGF in the disease has been better defined, anti-VEGF agents are being used as adjuncts to trabeculectomy.^49–52 The use of intravitreal bevacizumab prior to trabeculectomy has been reported to decrease postoperative hyphema and improve IOP outcomes after trabeculectomy. This is attributed to rapid regression of NVI after anti-VEGF therapy.⁵³ Improved ischemia and wound healing are other proposed mechanisms by which anti-VEGF agents improve surgical outcomes. However, in a study comparing patients undergoing trabeculectomy with and without intravitreal bevacizumab, the success rate 1 year after surgery was not statistically different between the 2 groups.⁵¹ In a another retrospective review, the reported surgical success rate for trabeculectomy with MMC and adjunctive intravitreal bevacizumab was 86.9% at 1 year and 51.3% at 5 years.⁵⁴ Lower preoperative IOP (<30 mmHg) indicating compromised aqueous production due to underlying ischemia and vitrectomy after trabeculectomy were identified as risk factors for surgical failure. Other studies report a success rate of 65% to 85% when trabeculectomy is combined with preoperative intravitreal bevacizumab as compared to 30% to 75% with trabeculectomy alone.^55–57 Furthermore, the mean IOP was found to be reduced by almost 66% 3 years after trabeculectomy with preoperative bevacizumab, although there was no significant change in visual acuity.⁵⁶ Similar to bevacizumab, use of intravitreal ranibizumab as an adjunct to trabeculectomy has also shown improvement in surgical outcomes.58

Glaucoma-drainage implants are commonly used in the management of patients with NVG as their success rate is less dependent on control of intraocular inflammation and presence of a filtering bleb. Success rates have ranged from 22% up to 97% with these devices.⁵⁹ In a retrospective study designed to assess the effectiveness of the Baerveldt glaucoma implant, there was adequate control of IOP, but postoperative visual loss was still common.⁶⁰ They reported a success rate of 79% at one year; 31% of patients remained stable or showed improvement in visual acuity, another 31% lost light perception vision. Younger age and poor preoperative visual acuity were associated with worse prognosis. In another report evaluating the Molteno implant for the same indication, success rates were reported to be 62% at 1 year and 10.3% at 5 years.⁶¹ Almost half of the patients lost light perception vision and 18% went into phthisis. The Ahmed valve was evaluated similarly in patients with NVG from proliferative diabetic retinopathy with a reported 3-year success rate of 62.5% in patients with a prior history of vitrectomy and 68.5% in patients with no prior history of vitrectomy.⁶² Intraocular silicone oil tamponade was noted as a risk factor for surgical failure.

As with trabeculectomy, use of preoperative anti-VEGF agents has been described to improve surgical results. In a comparison of preoperative intravitreal ranibizumab with Ahmed valve implantation vs Ahmed valve implantation alone, the success rate was 72.2% vs 68.4% at 12 months, respectively.⁶³ There were no significant differences in the 2 groups with respect to IOP control, visual acuity, and postoperative complications at 12 months. The authors concluded that a single intravitreal injection of ranibizumab (0.5 mg) before surgery had no significant effect on the medium- or long-term outcomes of Ahmed glaucoma valve implantation. However, in a meta-analysis of controlled clinical trials comparing Ahmed glaucoma valve implantation with or without preoperative intravitreal bevacizumab, the adjunctive treatment was found to be a safe and effective step associated with a numerically greater but not statistically significant IOP-lowering efficacy.⁶⁴ Additionally, the bevacizumab group was associated with significantly greater complete success rates and lower frequency of hyphema compared to the control group. Both groups were comparable in the reduction of glaucoma medication.

As trabeculectomy with mitomycin C and glaucoma drainage implants are the 2 most common procedures performed in patients with NVG, studies have compared surgical outcomes between the two. In a retrospective comparative case series, there was no statistically significant difference between trabeculectomy and Ahmed glaucoma valve in postoperative visual acuity, number of glaucoma medications, and IOP. Success was 60% and 55% at 2 years after Ahmed glaucoma valve implantation and trabeculectomy, respectively.⁶⁵ Similar findings were also reported in another study comparing the 2 surgical procedures.⁶⁶

In patients not controlled on topical therapy alone and who are poor surgical candidates because of limited visual potential or systemic reasons, cyclodestructive procedures offer a good alternative. Transscleral cyclophotocoagulation was first described in 1972.⁶⁷ Since then, the technique has evolved and most surgeons prefer to use diode laser compared to neodymium:yttrium-aluminum-garnet laser because of lower rates of phthisis (10% with neodymium:yttrium-aluminum-garnet laser and 0% with diode laser).⁶⁸ IOP reduction in the range of more than 50% may be achieved with diode laser cyclophotocoagulation;⁶⁹ however, postoperative pain and inflammation are common and need to be managed with topical steroids and cycloplegics. In addition, long-term hypotony and loss of light perception vision70 are possible, and hence, this procedure is generally reserved for patients with poor visual potential. A new laser modality called micropulse cyclophotocoagulation has recently become available. It is proposed to reduce the risk of postoperative pain, inflammation, and hypotony compared to traditional diode laser. Micropulse laser may potentially be used in eyes with good visual potential because of fewer postoperative complications, but there are no studies yet evaluating the effects of this laser long term. Direct application of laser to the ciliary processes with an endoscope has also been attempted, and in one study showed IOP lowering of up to 65%.^71,72 Alternatively, cyclocryotherapy can reduce IOP 50%, but there is a high incidence of vision loss, hypotony, inflammation, pain, retinal detachment, anterior segment ischemia, and phthisis bulbi.^73–75 In one study, 58% of patients lost light perception vision and 34% went into phthisis.⁷⁵ Surgical removal of part of the ciliary body has also been described but is associated with a high rate of complications.⁷⁶ In patients with painful eyes and no light perception vision, retrobulbar alcohol injection and enucleation can be attempted as a last resort.

Conclusion

NVG is a disease with potentially disastrous visual consequences. Early recognition and institution of treatment provides the patient with the best chance at preserving vision. Performing an undilated pupillary and iris exam with undilated gonioscopy is extremely important. A dilated retinal exam then needs to be performed to manage the source of the neovascularization. All efforts must be made to identify the disease before the angle is completely closed by the fibrovascular membrane. Performing PRP to eliminate the production of VEGF by ischemic retina is critical to the success of any antiglaucoma therapy, and intravitreal anti-VEGF therapies have more recently had a role in this process. Thereafter, one can start with topical and oral hypotensives, although most patients will end up requiring surgical intervention. Combining trabeculectomy or tube shunt surgery with preoperative anti-VEGF agents may help improve surgical outcomes, although more studies are required to substantiate these findings.

References

1.   Adair TH, Montani JP. Angiogenesis. San Rafael, CA: Morgan & Claypool Life Sciences; 2010.

2.   Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3(6):401-410.

3.   Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol. 2002;29(6 Suppl 16):15-18.

4.   Crawford TN, Alfaro DV III, Kerrison JB, Jablon EP. Diabetic retinopathy and angiogenesis. Curr Diabetes Rev. 2009;5(1):8-13.

5.   Fruttiger M. Development of the retinal vasculature. Angiogenesis. 2007;10(2):77-88.

6.   Witmer AN, Vrensen GF, Van Noorden CJ, Schlingemann RO. Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res. 2003;22(1):1-29.

7.   Ramakrishnan S, Anand V, Roy S. Vascular endothelial growth factor signaling in hypoxia and inflammation. J Neuroimmune Pharmacol. 2014;9(2):142-160.

8.   Wu Y, Lucia K, Lange M, Kuhlen D, Stalla GK, Renner U. Hypoxia inducible factor-1 is involved in growth factor, glucocorticoid and hypoxia mediated regulation of vascular endothelial growth factor-A in human meningiomas. J Neurooncol. 2014;119(2):263-273.

9.   Coats G. Further cases of thrombosis of central vein. Roy London Ophthalmol Hosp Rep. 1906;16:516-564.

10. Weiss DI, Shaffner RN, Nehrenberg TR. Neovascular glaucoma complicating carotid-cavernous fistula. Arch Ophthalmol. 1963;69:304-307.

11. Brown GC, Magargal LE, Schachat A, Shah H. Neovascular glaucoma. Etiologic considerations. Ophthalmology. 1984;91(4):315-320.

12. Sivak-Callcott JA, O’Day DM, Gass JD, Tsai JC. Evidence-based recommendations for the diagnosis and treatment of neovascular glaucoma. Ophthalmology. 2001;108(10):1767-1776.

13. Aiello LM, Wand M, Liang G. Neovascular glaucoma and vitreous hemorrhage after cataract surgery in patients with diabetes mellitus. Ophthalmology. 1983;90(7):814-820.

14. Rice TA, Michels RG, Maguire MG, Rice EF. The effect of lensectomy on the incidence of iris neovascularization and neovascular glaucoma after vitrectomy for diabetic retinopathy. Am J Ophthalmol. 1983;95(1):1-11.

15. Weinreb RN, Wasserstrom JP, Parker W. Neovascular glaucoma following neodymium-YAG laser posterior capsulotomy. Arch Ophthalmol. 1986;104(5):730-731.

16. Tripathi RC, Li J, Tripathi BJ, Chalam KV, Adamis AP. Increased level of vascular endothelial growth factor in aqueous humor of patients with neovascular glaucoma. Ophthalmology. 1998;105(2):232-237.

17. Sone H, Okuda Y, Kawakami Y, et al. Vascular endothelial growth factor level in aqueous humor of diabetic patients with rubeotic glaucoma is markedly elevated. Diabetes Care. 1996;19(11):1306-1307.

18. Meyer-Schwickerath R, Pfeiffer A, Blum WF, et al. Vitreous levels of the insulin-like growth factors I and II, and the insulin-like growth factor binding proteins 2 and 3, increase in neovascular eye diseases. Studies in nondiabetic and diabetic subjects. J Clin Invest. 1993;92(6):2620-2625.

19. Chen, KH, Wu CC, Roy S, Lee SM, Liu JH. Increased interleukin-6 in aqueous humor of neovascular glaucoma. Invest Ophthalmol Vis Sci. 1999;40(11):2627-2632.

20. Fiedler U, Reiss Y, Scharpfenecker M, et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med. 2006;12(2):235-239.

21. John T, Sassani JW, Eagle RC Jr. The myofibroblastic component of rubeosis iridis. Ophthalmology. 1983;90(6):721-728.

22. Gartner S, Taffet S, Friedman AH. The association of rubeosis iridis with endothelialisation of the anterior chamber: report of a clinical case with histopathological review of 16 additional cases. Br J Ophthalmol. 1977;61(4):267-271.

23. Goel M, Picciani RG, Lee RK, Bhattacharya SK. Aqueous humor dynamics: a review. Open Ophthalmol J. 2010;4:52-59.

24. Browning DJ, Scott AQ, Peterson CB, Warnock J, Zhang Z. The risk of missing angle neovascularization by omitting screening gonioscopy in acute central retinal vein occlusion. Ophthalmology. 1998;105(5):776-784.

25. Baseline and early natural history report. The Central Vein Occlusion Study. Central Vein Occlusion Study Group. Arch Ophthalmol. 1993;11(8):1087-1095.

26. Blinder KJ, Friedman SM, Mames RN. Diabetic iris neovascularization. Am J Ophthalmol. 1995;120(3):393-395.

27. Bloom PA, Papakostopoulos D, Gogolitsyn Y, Leenderz JA, Papakostopoulos S, Grey RH. Clinical and infrared pupillometry in central retinal vein occlusion. Br J Ophthalmol. 1993;77(2):75-80.

28. Maruyama Y, Kishi S, Kamei Y, Shimizu R, Kimura Y. Infrared angiography of the anterior ocular segment. Surv Ophthalmol. 1995;39(Suppl 1): S40-S48.

29. Sanborn GE, Symes DJ, Magargal LE. Fundus iris fluorescein angiography: evaluation of its use in the diagnosis of rubeosis iridis [published erratum appears in Ann Ophthalmol. 1986;18(4):155]. Ann Ophthalmol. 1986;18(2):52-58.

30. Ohnishi Y, Ishibashi T, Sagawa T. Fluorescein gonioangiography in diabetic neovascularisation. Graefes Arch Clin Exp Ophthalmol. 1994;232(4):199-204.

31. Sabates R, Hirose T, McMeel JW. Electroretinography in the prognosis and classification of central retinal vein occlusion. Arch Ophthalmol. 1983;101(2):232-235.

32. Larsson J, Andreasson S, Bauer B. Cone b-wave implicit time as an early predictor of rubeosis in central retinal vein occlusion. Am J Ophthalmol. 1998;125(2):247-249.

33. Anchala AR, Pasquale LR. Neovascular glaucoma: a historical perspective on modulating angiogenesis. Semin Ophthalmol. 2009;24(2):106-112.

34. Kim M, Lee C, Payne R, Yue BY, Chang JH, Ying H. Angiogenesis in glaucoma filtration surgery and neovascular glaucoma: a review. Surv Ophthalmol. 2015;60(6):524-535.

35. 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(11):1350-1354.

36. Cashwell LF, Marks WP. Panretinal photocoagulation in the management of neovascular glaucoma. South Med J. 1988;81(11):1364-1368.

37. Allen RC, Bellows AR, Hutchinson BT, Murphy SD. Filtration surgery in the treatment of neovascular glaucoma. Ophthalmology. 1982;89(10):1181-1187.

38. Fernández-Vigo J, Castro J, Macarro A. Diabetic iris neovascularization. Natural history and treatment. Acta Ophthalmol Scand. 1997;75(1):89-93.

39. Sihota R, Sandramouli S, Sood NN. A prospective evaluation of anterior retinal cryoablation in neovascular glaucoma. Ophthalmic Surg. 1991;22(5):256-259.

40. Stefaniotou M, Paschides CA, Psilas K. Panretinal cryopexy for the management of neovascularization of the iris. Ophthalmologica. 1995;209(3):141-144.

41. Vernon SA, Cheng H. Panretinal cryotherapy in neovascular disease. Br J Ophthalmol. 1988;72(6):401-405.

42. Tsai JC, Bloom PA, Franks WA, Khaw PT. Combined transscleral diode laser cyclophotocoagulation and transscleral retinal photocoagulation for refractory neovascular glaucoma. Retina. 1996;16(2):164-166.

43. Flaxel CJ, Larkin GB, Broadway DB, Allen PJ, Leaver PK. Peripheral transscleral retinal diode laser for rubeosis iridis. Retina. 1997;17(5):421-429.

44. Fong DS, Girach A, Boney A. Visual side effects of successful scatter laser photocoagulation surgery for proliferative diabetic retinopathy: a literature review. Retina. 2007;27(7):816-824.

45. Tsai JC, Feuer WJ, Parrish RK II, Grajewski AL. 5-Fluorouracil filtering surgery and neovascular glaucoma. Long-term follow-up of the original pilot study. Ophthalmology. 1995;102(6):887-892; discussion 892-893.

46. Katz GJ, Higginbotham EJ, Lichter PR, et al. Mitomycin C versus 5-fluorouracil in high-risk glaucoma filtering surgery. Extended follow-up. Ophthalmology. 1995;102(9):1263-1269.

47. Kiuchi Y, Sugimoto R, Nakae K, Saito Y, Ito S. Trabeculectomy with mitomycin C for treatment of neovascular glaucoma in diabetic patients. Ophthalmologica. 2006;220(6):383-388.

48. Takihara Y, Inatani M, Fukushima M, Iwao K, Iwao M, Tanihara H. Trabeculectomy with mitomycin C for neovascular glaucoma: prognostic factors for surgical failure. Am J Ophthalmol. 2009;147(5):912-918.

49. Saito Y, Higashide T, Takeda H, Ohkubo S, Sugiyama K. Beneficial effects of preoperative intravitreal bevacizumab on trabeculectomy outcomes in neovascular glaucoma. Acta Ophthalmol. 2010;88(1):96-102.

50. Chen CH, Lai IC, Wu PC, et al. Adjunctive intravitreal bevacizumab-combined trabeculectomy versus trabeculectomy alone in the treatment of neovascular glaucoma. J Ocul Pharmacol Ther. 2010;26(1):111-118.

51. Takihara Y, Inatani M, Kawaji T, et al. Combined intravitreal bevacizumab and trabeculectomy with mitomycin C versus trabeculectomy with mitomycin C alone for neovascular glaucoma. J Glaucoma. 2011;20(3):196-201.

52. Gupta V, Jha R, Rao A, Kong G, Sihota R. The effect of different doses of intracameral bevacizumab on surgical outcomes of trabeculectomy for neovascular glaucoma. Eur J Ophthalmol. 2009;19(3):435-441.

53. Davidorf FH, Mouser JG, Derick RJ. Rapid improvement of rubeosis iridis from a single bevacizumab (Avastin) injection. Retina. 2006;26(3):354-356.

54. Higashide T, Ohkubo S, Sugiyama K. Long-term outcomes and prognostic factors of trabeculectomy following intraocular bevacizumab injection for neovascular glaucoma. PLoS One. 2015;10(8):e0135766.

55. Miki A, Oshima Y, Otori Y, Matsushita K, Nishida K. One-year results of intravitreal bevacizumab as an adjunct to trabeculectomy for neovascular glaucoma in eyes with previous vitrectomy. Eye (Lond). 2011;25(5):658-659.

56. Kobayashi S, Inoue M, Yamane S, Sakamaki K, Arakawa A, Kadonosono K. Long-term outcomes after preoperative intravitreal injection of bevacizumab before trabeculectomy for neovascular glaucoma. J Glaucoma. 2016;25(3):281-284.

57. Hyung SM, Kim SK. Mid-term effects of trabeculectomy with mitomycin C in neovascular glaucoma patients. Korean J Ophthalmol. 2001;15(2):98-106.

58. Kitnarong N, Sriyakul C, Chinwattanakul S. A prospective study to evaluate intravitreous ranibizumab as adjunctive treatment for trabeculectomy in neovascular glaucoma. Ophthalmol Ther. 2015;4(1):33-41.

59. Assaad MH, Baerveldt G, Rockwood EJ. Glaucoma drainage devices: pros and cons. Curr Opin Ophthalmol. 1999;10(2):147-153.

60. Sidoti PA, Dunphy TR, Baerveldt G, et al. Experience with the Baerveldt glaucoma implant in treating neovascular glaucoma. Ophthalmology. 1995;102(7):1107-1118.

61. Mermoud A, Salmon JF, Alexander P, Straker C, Murray AD. Molteno tube implantation for neovascular glaucoma. Long-term results and factors influencing the outcome. Ophthalmology. 1993;100(6):897-902.

62. Park UC, Park KH, Kim DM, Yu HG. Ahmed glaucoma valve implantation for neovascular glaucoma after vitrectomy for proliferative diabetic retinopathy. J Glaucoma. 2011;20(7):433-438.

63. Tang M, Fu Y, Wang Y, et al. Efficacy of intravitreal ranibizumab combined with Ahmed glaucoma valve implantation for the treatment of neovascular glaucoma. BMC Ophthalmol. 2016;16:7.

64. Zhou M, Xu X, Zhang X, Sun X. Clinical outcomes of Ahmed glaucoma valve implantation with or without intravitreal bevacizumab pretreatment for neovascular glaucoma: a systematic review and meta-analysis. J Glaucoma. 2016;25(7):551-557.

65. Shen CC, Salim S, Du H, Netland PA. Trabeculectomy versus Ahmed glaucoma valve implantation in neovascular glaucoma. Clin Ophthalmol. 2011;5:281-286.

66. Im YW, Lym HS, Park CK, Moon JI. Comparison of mitomycin C trabeculectomy and Ahmed valve implant surgery for neovascular glaucoma. J Korean Ophthalmol Soc. 2004;45:1515-1521.

67. Beckman H, Waeltermann J. Transscleral ruby laser cyclocoagulation. Am J Ophthalmol. 1984;98:788-795.

68. Oguri A, Takahashi E, Tomita G, Yamamoto T, Jikihara S, Kitazawa Y. Transscleral cyclophotocoagulation with the diode laser for neovascular glaucoma. Ophthalmic Surg Lasers. 1998;29(9):722-727.

69. Bloom PA, Tsai JC, Sharma K, et al. “Cyclodiode.” Transscleral diode laser cyclophotocoagulation in the treatment of advanced refractory glaucoma. Ophthalmology. 1997;104(9):1508-1519; discussion 1519-1520.

70. Eid TE, Katz LJ, Spaeth GL, Augsburger JJ. Tube-shunt surgery versus neodymium:YAG cyclophotocoagulation in the management of neovascular glaucoma. Ophthalmology. 1997;104(10):1692-1700.

71. Uram M. Ophthalmic laser microendoscope ciliary process ablation in the management of neovascular glaucoma. Ophthalmology. 1992;99(12):1823-1828.

72. Lima FE, Magacho L, Carvalho DM, Susanna R Jr, Avila MP. A prospective, comparative study between endoscopic cyclophotocoagulation and the Ahmed drainage implant in refractory glaucoma. J Glaucoma. 2004;13(3):233-237.

73. Bietti G. Surgical intervention on the ciliary body; new trends for the relief of glaucoma. J Am Med Assoc. 1950;142(12):889-897.

74. Feibel RM, Bigger JF. Rubeosis iridis and neovascular glaucoma. Evaluation of cyclocryotherapy. Am J Ophthalmol. 1972;74(5):862-867.

75. Krupin T, Johnson MF, Becker B. Anterior segment ischemia after cyclocryotherapy. Am J Ophthalmol. 1977;84(3):426-428.

76. Sautter H, Demeler U. Antiglaucomatous ciliary body excision. Am J Ophthalmol. 1984;98(3):344-348.

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