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1 Metadata of the chapter that will be visualized in Online Series Title Chapter Title Glaucomas: Neovascular Glaucoma Chapter SubTitle Copyright Year 2010 Copyright Holder Springer-Verlag Berlin Heidelberg Corresponding Author Family Name Wenick Particle Given Name Adam S Suffix Division Wilmer Eye Institute Organization Johns Hopkins Hospital Address 600 N Wolfe Street, Wilmer B20, , Baltimore, MD, USA awenick1@jhmi.edu Author Family Name Particle Given Name Suffix Division Organization Address Robin Alan L Wilmer Eye Institute Johns Hopkins Hospital 600 N Wolfe Street, Wilmer B20, , Baltimore, MD, USA Abstract The mainstays of medical treatment for neovascular glaucoma (NVG) are aqueous suppressants, topical steroids, and cycloplegics. Preliminary results suggest that antivascular endothelial growth factor (VEGF) therapy has a role in the treatment of NVG as a bridge to pan-retinal photocoagulation (PRP) and surgery. Prompt PRP or other relevant treatment of underlying disease is vital to the preservation of vision in NVG. PRP should ideally be performed 2 3 weeks prior to glaucoma surgery to allow for surgery in an uninflamed eye with regressed neovascularization (NV). Tube shunts are usually the preferred surgical technique in NVG, but trabeculectomy can be as effective in eyes with angle closure and regressed NV. Currently, cyclophotocoagulation is generally reserved for eyes with poor visual potential or which have failed other treatment modalities, but the low rates of phthisis with current approaches warrant its further consideration for the treatment of NVG in specific cases. Despite regression of NV from effective PRP or anti-vegf therapy, surgery is still required to control NVG if angle closure has developed. The most common cause of treatment failure in NVG is progression of underlying disease.

2 1 2 Glaucomas: Neovascular Glaucoma Adam S. Wenick and Alan L. Robin Core Messages The mainstays of medical treatment for neovascular glaucoma (NVG) are aqueous suppressants, topical steroids, and cycloplegics. Preliminary results suggest that antivascular endothelial growth factor (VEGF) therapy has a role in the treatment of NVG as a bridge to panretinal photocoagulation (PRP) and surgery. Prompt PRP or other relevant treatment of underlying disease is vital to the preservation of vision in NVG. PRP should ideally be performed 2 3 weeks prior to glaucoma surgery to allow for surgery in an uninflamed eye with regressed neovascularization (NV). Tube shunts are usually the preferred surgical tech nique in NVG, but trabeculectomy can be as effective in eyes with angle closure and regressed NV. Currently, cyclophotocoagulation is generally reserved for eyes with poor visual potential or which have failed other treatment modalities, but the low rates of phthisis with current approaches warrant its further consideration for the treatment of NVG in specific cases What Medications Can Be Used to Control Neovascular Glaucoma? Topical and oral medical therapies are the initial treatment of choice to lower intraocular pressure (IOP) and limit vision loss and pain secondary to neovascular glaucoma (NVG) IOP Lowering Agents Therapies aimed at decreasing aqueous production (beta-blockers, topical and systemic carbonic anhydrase inhibitors, and alpha adrenergics) have the soundest rationale for use in NVG. No study is available in the literature comparing effectiveness of these various medications in NVG, and they are often required in combination. If the IOP is markedly elevated, it would not be inappropriate to commence simultaneously with an alpha-agonist, topical nonselective beta blocker, and topical carbonic anhydrase inhibitor. The use of oral carbonic anhydrase inhibitors (acetazolamide) in place of or in combination with topical therapy (dorzolamide or brinzolamide) is often employed in the acute setting, and conflicting reports exist regarding their relative effectiveness. While Maus A. S. Wenick ( ) Wilmer Eye Institute, Johns Hopkins Hospital, 600 N Wolfe Street, Wilmer B20, Baltimore, MD , USA awenick1@jhmi.edu Despite regression of NV from effective PRP or anti-vegf therapy, surgery is still required to control NVG if angle closure has developed. The most common cause of treatment failure in NVG is progression of underlying disease J. A. Giaconi (eds.), Pearls of Glaucoma Management, DOI: / _49, Springer-Verlag Berlin Heidelberg 2009 Giaconi_49.indd Chap1 5/11/2009 1:32:47 PM

3 A. S. Wenick and A. L. Robin [1] found oral acetazolamide to be more effective in reducing aqueous production and IOP than 2% topical dorzolamide in normal subjects, Rosenberg [2] found no difference in their effectiveness and no additive benefit of using both agents in combination in subjects with primary open angle glaucoma or ocular hypertension. Neither study found the combination of oral and topical carbonic anhydrase inhibitors to be more effective than oral therapy alone. It should be noted that both studies were performed in eyes with relatively normal anterior segments. The absorption and penetration of topical agents in eyes with an altered cornea, an altered anterior segment, and aqueous humor have not been well studied previously. It is unclear how these results extrapolate to NVG, where IOPs tend to be significantly higher than those in the studies cited above. Close monitoring of electrolytes should be employed with the long-term use of oral carbonic anhydrase inhibitors in this patient population that tends to have a high prevalence of concomitant renal disease, especially if patients are also taking thiazide or loop diuretics. It should be remembered that approximately two-thirds of subjects who use oral agents long term are unable to tolerate them due to systemic adverse events. If the above therapies are ineffective, osmotic agents such as intravenous mannitol 1 2 g/kg can be used to further lower pressure in the acute setting for both the patient s comfort and to improve visualization of the angle. However, osmotics may have limited efficacy in NVG due to breakdown of the blood-vitreous barrier. Caution and close monitoring of serum electrolytes and renal function should be employed with these agents. There is no data available regarding the use of prostaglandin analogues in NVG. However their effectiveness is questionable, as the uveal outflow path may be covered with neovascular membrane [3, 4]. Additionally, the use of prostaglandins could theoretically increase inflammation in NVG. There is no role for the use of topically administered muscarinic agents, as closed angles or membranes covering the trabecular meshwork render them ineffective [3]. Not only is IOP not typically lowered by these agents, but they may cause increased inflammation and discomfort [4, 5] and worsen synechial angle closure [4] Anti-Inflammatory and Anti- Angiogenic Medications Frequent administration of topical corticosteroid medications are recommended to reduce inflammation that is inevitably present [3]. There is minimal data on the role of oral steroids for this purpose, and it must be remembered that oral steroids could have significant adverse effects in diabetic patients. Intravitreal corticosteroid injections have also been proposed as a useful adjunctor primary therapy in the treatment of NVG [6]. Jonas treated four eyes with NVG caused by central retinal vein occlusion (CRVO) or proliferative diabetic retinopathy (PDR) with injection of 20 mg of crystalline triamcinolone acetonide alone and found that all four eyes had a marked decrease in rubeosis iridis with lowering of mean IOP from 26.5 ± 12.1 to ± 11.3 mmhg. However one of these eyes with initial IOP of 40 mmhg demonstrated no decrease in IOP after injection [6]. The use of intravitreal steroids remains unproven and no large scale trials have yet confirmed these initial results. The use of oral, topical, periocular, or intraocular steroids is certainly indicated for the treatment of the underlying disease in NVG caused by uveitic processes. Antivascular endothelial growth factor (VEGF) therapy shows promise in the treatment of NVG and is discussed further below Cycloplegics/Mydriatics Topical atropine sulfate 1% may be used for symptomatic relief of pain in NVG. It may also have some effect in lessening inflammation [7] and possibly in increasing aqueous outflow through the uveoscleral route, if this pathway is not blocked by fibrovascular membranes [4]. IOP lowering alone may decrease ischemia and therefore decrease the stimulus for neovascularization (NV) [8] ; but prompt medical or laser treatment of the underlying disorder is critical to prevent formation of peripheral anterior synechiae (PAS) and angle closure. Once extensive PAS have formed, surgical treatment is usually required to control IOP, despite regression of NV, as topical agents are rarely sufficiently effective once PAS have formed Giaconi_49.indd Chap2 5/11/2009 1:32:47 PM

4 49 Glaucomas: Neovascular Glaucoma Summary for the Clinician Aqueous suppressants, beta-blockers, carbonic anhydrase inhibitors (topical and oral), and alpha adrenergics are the mainstay of treatment for the lowering of IOP in NVG. Oral acetazolamide and intravenous mannitol may be used with caution in the patient population due to a high prevalence of concomitant renal disease. Intense topical corticosteroids are recommended to quell the prominent inflammatory response in NVG. Topical atropine is also recommended for symptomatic relief and may decrease IOP and inflammation in NVG. Failure of medical therapy alone is the rule in advanced NVG What Is the Surgical Treatment of Choice for Neovascular Glaucoma? Should Everyone Always Get a Tube Shunt to Control IOP, i.e., Can a Trabeculectomy Be Useful? The three modalities most often employed when medical treatment fails to control IOP in NVG are tube shunts, trabeculectomy, and cycloablation. There is no role for laser trabeculoplasty in these highly abnormal angles. Almost 30 years ago, Simmons attempted to actually coagulate the angle s vessels, but produced vascular spasm and minimal long-term coagulation [9, 10]. Understanding the pathogenesis and disease course of NVG is vital to understanding the surgical choices and reasons for surgical failures. In the initial stages of NVG, fibrovascular tissue grows over the trabecular meshwork leading to decreased aqueous outflow and increased IOP. Next, myofibroblasts present in the neovascular tissue proliferate and contract, leading to progressive permanent angle closure and progressive increase in IOP. Corneal endothelial proliferation can also extend over the angle [11]. When deciding upon the best surgical option for a patient who has failed medical therapy and when analyzing the surgical literature, it is important to keep the above in mind and note that NVG is not a homogenous disease. Surgical failure in NVG is usually defined as an inability to control IOP, as well as the development of phthisis and/or loss of light perception, regardless of the specific etiology of the latter. While phthisis and loss of light perception can occur from glaucomatous damage due to high IOP or as a complication of glaucoma surgery, progression of underlying ischemic disease, rather than failure to control IOP, is the most common cause of failure of surgeries for NVG [12]. It is therefore important to interpret study results in the context of the natural history of the underlying disease. The ideal surgical treatment is influenced by the underlying disorder as well as the clinical characteristics of each patient i.e., IOP, presence of active vs. regressed NV, prior laser or VEGF therapy, prior intraocular surgical therapies, degree of inflammation, degree of angle closure, presence of hazy ocular media, and visual potential. Outcomes tend to be better in PDR compared to CRVOs [13], and ocular ischemic syndrome has the worst prognosis [3]. A majority of the literature concerning the surgical treatment of NVG consists of retrospective noncomparative case series [4]. Few comparative series and no prospective comparative studies or randomized trials exist in the literature (Tables 49.1 and 49.2 ). Comparing techniques in these different series is impossible due to different measures of successful outcome, differing and insufficient follow up times, and different baseline patient characteristics, including differences in etiology of NVG, baseline visual function, degree of NVA and PAS, and percentage of patients who have undergone pan-retinal photocoagulation (PRP). In many of these reports, all of these details are not even available. Early studies with cyclocryoablation reported a large percentage of patients with vision loss and phthisis [35], relegating the use of cyclocryoablation and cyclophotocoagulation only to eyes with limited visual potential [4]. These early studies did not employ graduated cycloablation, which results in better outcomes [36, 37] and which some advocate as primary therapy in some cases even when there is good visual potential [3]. The bias towards using cycloablation only in eyes with poor visual potential, combined with the retrospective nature of studies in the literature has led to a reinforcement of the belief that cycloablation should only be used when visual prognosis is poor. Eid found better outcomes with tube shunts compared to Giaconi_49.indd Chap3 5/11/2009 1:32:47 PM

5 A. S. Wenick and A. L. Robin AQ Sidoti [8] cyclophotocoagulation in a retrospective study in which patients were matched in terms of underlying disease. However, in the cyclophotocoagulation group only 4.2% of patients had a visual acuity better than count fingers, while in the tube shunt group 41.7% of patients had vision better than count fingers. Additionally, a larger proportion of patients in the cyclophotocoagulation group had 360 of angle closure [17], bringing the conclusions of this report into question. Currently, most glaucoma specialists recommend cyclophotocoagulation only in eyes with poor visual prognosis or when other methods have failed to control IOP. However, further studies are needed to evaluate the role of graduated cyclophotocoagulation in NVG, as some promising results have been published [37]. A study by Tsai reporting poor long-term Eid [17] a Minkler [18] Lloyd [19] Downes [20] Freedman [21] Ancker [22] results of trabeculectomy with 5-FU in NVG 5 year survival rate of filtering surgery with 5-FU was only 28% is often cited as a rational for using tube shunts rather then trabeculectomy for NVG [11]. However these results are similar to long-term results with tube shunts (Tables 49.1 and 49.2 ) [13, 14]. The use of mitomycin C (MMC) may give superior results to 5-FU, though one small study found no difference between the two antimetabolites in NVG [38]. As mentioned above, failure of glaucoma surgery in NVG is most commonly caused by progression of underlying disease, and poor outcomes at 5 yearslikely represent this phenomenon rather than problems intrinsic to any one technique. In uninflammed NVG eyes treated with previous PRP, NVG becomes similar to uncomplicated angle closure and good results can be expected with Faghihi [23] Chalam [24] a Krupin Krupin Baerveldt Tube shunt b Molteno Molteno Molteno Molteno Molteno PPV + Ahmed PPV + Baerveldt 54(60) 38(38) 27(27) 92(92) 40(40) 79(79) 36(36) 24(24) 15(15) 18(18) 50(50) 18(18) 36(36) 17(18) 18(18) Table 49.1 Studies of NVG and tube shunt surgery Study Mermoud Yalvac Yalvac Susanna Krupin Krupin [13] [14] a [14] a [15] [5] [16] Technique Molteno Ahmed Molteno Ahmed + MMC Number of patients (eyes) IOP Mean age NR Mean followup (months) Percentage of 62.1, 52.9, 63.2, 43.1, 30.8, 56.2, 37.0, 29.6, d 79, success 10.3 c 43.2, 37.8, 25.2 c 29.6, 29.6, 29.6 c Criteria IOP IOP IOP IOP IOP IOP IOP IOP < 22e IOP IOP IOP <20 g IOP for < 22 e 6 21 e 6 21 e 5 21 f < 25 e < 25 e 6 21 e 6 25 e 6 21 e < 26 e < 22 e 5 21 e 6 21 success PRP/cryo NR NR NR NR NR NR (%) DR NR NR RVO NR NR Other NR NR NR data not reported acomparative study b Molteno, Ahmed, Baerveldt, or Schocket c Kaplan-Meier life-table success at 1, 2, 3, 4, 5 years d Kaplan-Meier life-table success at 12 and 18 months e ± IOP lowering drops, no phthisis, no further surgery f With at least 30% reduction in IOP, ± IOP lowering drops, no phthisis gwithout medications Giaconi_49.indd Chap4 5/11/2009 1:32:47 PM

6 49 Glaucomas: Neovascular Glaucoma Table 49.2 Studies of NVG and filtering surgery Study Allen [7] Technique Trab/ PLS Number of patients (eyes) Euswas [25] Mandal [26] Kiuchi [27] Herschler [28] Elgin [12] TMMC TMMC TMMC Trab TMMC + iris cauterization Tsai [11] trabeculectomy [29, 30]. That being said, younger eyes [11] and eyes with prior vitrectomy [27] tend to fare worse with trabeculectomy. The ability of anti-vegf agents to induce rapid regression of NV of the angle and iris (discussed below) may lead to an expanded role for trabeculectomy in NVG. As noted above, for many glaucoma specialists, tube shunts have become the treatment of choice for NVG. While trabeculectomy is a viable option in quiet eyes with regressed NV, tubes shunts seem to be a better choice in inflamed eyes where failure rates of Flanagan [29] Clearkin [30] Lee [31] Fernandez- Vigo [32] Kiuchi [33] PG trabeculectomy are highest. While many advocate the use of one type of tube over others, the results with different devices are roughly equivalent [39] (see Table 49.1 ). As with trabeculectomy, tube shunt results are worse when used for NVG than for other types of glaucoma [40]. It is recommended that tube shunts be placed as far posterior as possible, i.e., at the pars plana in eyes that have undergone vitrectomy and in the sulcus in pseudophakic eyes. This will help to avoid corneal decompensation and blockage of tubes from neovascular membranes. Kiuchi [33] PC Kono [34] Trab/ Trab Trab Modified Trab PPV+ PPV + PLS + Trab filtering 5-FU 22(24) 21(23) 14(15) 35(35) 13(13) 72(72) 34(34) 6(6) 6(6) 5(5) 23(26) 9(9) 16(16) 18(21) Mean age Mean followup (months) NR Percentage , , , 27c 55.6, 81.3, 81.3, 90.5 of success 61.8, 61.8 a 67, 61, 41, 28 b 18.5? a 81.3 a Criteria IOP IOP IOP IOP IOP IOP IOP useful IOP IOP IOP IOP IOP IOP for < 25 d < 22 d < 22 e < 22 d 6 26 f < 23 d < 22 d vision < 22 d 4 20 d < 23 f < 22 d < 22 d 5 21 d success PRP/cryo g NR NR (%) DR RVO Other PLS posterior lip sclerotomy; TMMC trabeculectomy with mitomycin C; NR data not reported. PG proliferative group-vitreous hemorrhage, fibrovascular membrane, and/or retinal detachment. PC NVG but no vitreous hemorrhage, fibrovascular membrane, or retinal detachment a Kaplan-Meier life-table success at 12, 24 and 36 months b Kaplan-Meier life-table success at 1, 2, 3, 4, 5 years c Percentage success at 12 and 24 months d ± IOP lowering drops, no phthisis, no further surgery ewithout medications f ± IOP lowering drops, allowed additional surgery gafter filtering surgery Giaconi_49.indd Chap5 5/11/2009 1:32:48 PM

7 A. S. Wenick and A. L. Robin Summary for the Clinician Comparison of surgical techniques to treat NVG is severely limited due to a dearth of comparative and prospective studies as well as differing outcome measures and baseline patient characteristics in various studies. Though tube shunts are considered by many to be the surgical treatment of choice in NVG, trabeculectomy and tube shunts are likely equivalent in quiet eyes with regressed NV. Tubes shunts or cycloablation are more likely to be effective in inflamed eyes with active NV. Cycloablation is most often employed only in eyes with poor visual potential, but graduated cyclophotocoagulation may have a primary role in treatment of eyes with good visual potential, and its use should be further investigated. Over the long term, all surgical techniques share poor outcomes in NVG in large parts due to progression of underlying disease How Should PRP and Glaucoma Surgery Be Timed? Determining the timing of PRP with relation to surgery must take into account the characteristics of the individual patient s disease. Factors such as media opacities and significantly elevated IOP, despite maximal medical therapy, may lead to glaucoma surgery sooner than would otherwise be desired. Ideally if given the luxury, PRP should be performed 2 3 weeks prior to filtering or tube implant surgery. This allows adequate time for the beneficial effects of PRP to take effect, including regression of iris and angle NV and a decrease in ocular inflammation, reducing the rates of intraoperative complications (hyphema) and early complications due to a prominent inflammatory response (such as bleb failure) [7, 12, 26, 29]. Eyes with previously healthy optic nerves likely can tolerate IOP in the mid 30s during this period after PRP. Already severely damaged optic nerves, from asymptomatic IOP elevation or from POAG for instance, may not be able to tolerate these same IOPs for 2 3 weeks without further significant optic neuropathy [7]. Inability to control IOP to at least these levels (the mid 30s) is an indication for prompt glaucoma surgery. The clinician must also keep in mind that PRP can lead to a further increase in IOP [3], necessitating close follow-up in the interim period. Recently Euswas and Warrasak published promising results in which PRP was delayed until at least 1 week after trabeculectomy with mitomycin-c because of hazy ocular media [25]. In their consecutive series of 21 patients and 23 eyes, they had a qualified success rate of 91.3% with follow-up of months (mean 29 ± 11.3) [25]. Finally early data from the use of anti-vegf agents indicate that their use may obviate the need to wait for PRP to take effect prior to glaucoma surgery, as discussed below. Summary for the Clinician PRP should if possible, precede glaucoma surgery by 2 3 weeks to allow for regression of NV prior to surgical intervention, but this is often not possible due to hazy ocular media or significantly elevated IOP despite maximal medical management Is Bevacizumab Useful in Neovascular Glaucoma? What Kind of Results and Time-Course Can I Expect from Its Use? For NV of the Iris, Should It Be Injected into the Anterior Chamber or Vitreal Cavity? Multiple case reports /case series have been published showing promising results with the use of both intravitreal and intracameral bevacizumab (Figs and 49.2 ) in cases of iris NV and NVG secondary to PDR, CRVO, ocular ischemic syndrome, and radiation retinopathy [41 52]. In the largest of these studies, Avery studied the effects of intravitreal bevacizumab (6.25 m g 1.25 mg) on 45 eyes of 32 patients with iris or retinal NV from PDR. Of the 11 eyes with iris NV, 9 eyes (82%) showed complete regression of NV, while the remaining 2 eyes showed only partial regression Giaconi_49.indd Chap6 5/11/2009 1:32:48 PM

8 49 Glaucomas: Neovascular Glaucoma Table 49.3 Doses used for bevacizumab in neovascular glaucoma Anterior chamber dose 1.25 mg/0.05 ml 1.00 mg/ 0.04 ml Posterior chamber dose 0.5 mg/0.2 ml Fig Bevacizumab prepared for intravitreal injection by the chemotherapy pharmacist Fig A patient receiving intravitreal bevacizumab for neovascularization of the angle and iris due to proliferative diabetic retinopathy Leakage on iris flourescein angiogram was noted to diminish in as little as 24 h. Recurrent leakage was seen as early as 2 weeks following injection and effects lasted up to the maximum follow-up time of 11 weeks in some eyes. Effects on IOP were not reported in this paper, nor were the number of eyes with NVG [43]. The largest consecutive case series looking at the use of bevacizumab specifically in NVG was reported by Iliev (retinal vein occlusions) [47] and Gheith (PDR and CRVOs) [45] (Table 49.3 ). Both reviews included six consecutive patients who were given injections of 1.25 mg of intravitreal bevacizumab. In the study by Iliev, all cases showed marked regression of anterior segment NV, relief of symptoms within 48 h, while substantial lowering of IOP occurred in 3 of 6 eyes. Adjuvant cyclophotocoagulation was performed in the remaining 3, and subsequent PRP was performed in all eyes. The follow-up period was 4 16 weeks, and all patients had stable or improved vision, regression of angle and iris NV, and resolution of pain and anterior chamber inflammation at the end of follow-up [47]. In the study by Gheith with a follow up period of 3 19 months (average 9.7 months), all cases showed complete regression of iris and angle NV with lowering of IOP at 1 week. Subsequent PRP was done at this time. Iris NV recurred in one case at 3 months and in a second case at 5 months. IOP was controlled with topical agents in cases without PAS, but subsequent glaucoma surgery (tube shunt or TMMC) was required to control IOP in patients with PAS [45]. Similar results were reported in the only published study in which intracameral bevacizumab was used [46]. These findings suggest that intracameral bevacizumab is most useful in NVG when given before PAS form and cause permanent damage to the aqueous outflow pathways.in all studies, no adverse effects were reported. As discussed by the authors cited above, bevacizumab seems to be a promising adjunct to PRP in the treatment of NVG. The duration of action is unknown and it is likely that repeat injections would be required to control NVG when used as a sole agent. The transient effects of current anti-vegf treatments make their use most promising as a temporizing measure until PRP results can take effect, or prior to glaucoma surgery. When using intravitreal or intracameral bevacizumab, AQ2 AQ3 Giaconi_49.indd Chap7 5/11/2009 1:32:48 PM

9 A. S. Wenick and A. L. Robin it is important to keep in mind the short term elevation in IOP that may occur after injection [53]. The finding that at least moderate amounts of IOP rise are to be expected immediately after injection [53] may necessitate paracentesis in eyes with already markedly elevated IOP from NVG prior to any intraocular injection. However one should keep in mind that hemorrhagic complications (including hyphema and suprachoroidal hemrrhage) may occur with acute reduction of IOP by paracentesis. Additionally, one should be aware that long term elevation in IOP has been reported as an uncommon side effect after injection of intravitreal bevacizumab [53, 54]. Summary for the Clinician Cursory studies of the use of intravitreal bevacizumab in NVG have shown promising results, but better controlled studies with longer follow up are needed to establish its role in the treatment of NVG. Results in terms of regression of NV, decrease in inflammation, and lowering of IOP can be expected in as little as 48 h after injection of bevacizumab. Despite the dramatic effects that have been reported with intraocular bevacizumab in NVG, surgery is still required if significant angle closure has developed. Currently, given its rapid onset of efficacy but short duration of action, intraocular anti- VEGF therapy is most useful as a bridge or adjunct to PRP and glaucoma surgery rather than a definitive treatment for NVG. References 1. Maus TL, Comparison of dorzolamide and acetazolamide as suppressors of aqueous humor flow in humans. Arch Ophthalmol 1997 ;115(1): Rosenberg LF, Combination of systemic acetazolamide and topical dorzolamide in reducing intraocular pressure and aqueous humor formation. Ophthalmology 1998 ;105(1): 88 92; discussion Hayreh SS. Neovascular glaucoma. Prog Retin Eye Res 2007 ;26(5): Sivak-Callcott JA, Evidence-based recommendations for the diagnosis and treatment of neovascular glaucoma. Ophthalmology 2001 ;108(10): ; quiz 1777, Krupin T, Filtering valve implant surgery for eyes wtih neovascular glaucoma. Am J Ophthalmol 1980 ;89(3): Jonas JB, Regression of neovascular iris vessels by intravitreal injection of crystalline cortisone. J Glaucoma 2001 ;10(4): Allen RC, Filtration surgery in the treatment of neovascular glaucoma. Ophthalmology 1982 ;89(10): Sidoti PA, Experience with the Baerveldt glaucoma implant in treating neovascular glaucoma. Ophthalmology 1995 ;102(7): Simmons RJ, Deppermann SR, Dueker DK. The role of gonio-photocoagulation in neovascularization of the anterior chamber angle. Ophthalmology 1980 ;87(1): Simmons RJ, Goniophotocoagulation for neovascular glaucoma. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol 1977 ;83(1): Tsai JC, 5-Fluorouracil filtering surgery and neovascular glaucoma. Long-term follow-up of the original pilot study. Ophthalmology 1995 ;102(6): ; discussion Elgin U, Trabeculectomy with mitomycin C combined with direct cauterization of peripheral iris in the management of neovascular glaucoma. J Glaucoma 2006 ;15(5): Mermoud A, Molteno tube implantation for neovascular glaucoma. Long-term results and factors influencing the outcome. Ophthalmology 1993 ;100(6): Yalvac IS, Long-term results of Ahmed glaucoma valve and Molteno implant in neovascular glaucoma. Eye 2007 ; 21 (1): Susanna R Jr. Partial Tenon s capsule resection with adjunctive mitomycin C in Ahmed glaucoma valve implant surgery. Br J Ophthalmol 2003 ;87(8): Krupin T, Long-term results of valve implants in filtering surgery for eyes with neovascular glaucoma. Am J Ophthalmol 1983 ;95(6): Eid TE, Tube-shunt surgery versus neodymium:yag cyclophotocoagulation in the management of neovascular glaucoma. Ophthalmology 1997 ;104(10): Minckler DS, Clinical experience with the single-plate Molteno implant in complicated glaucomas. Ophthalmology 1988 ;95(9): Lloyd MA, Clinical experience with the single-plate Molteno implant in complicated glaucomas. Update of a pilot study. Ophthalmology 1992 ;99(5): Downes RN, The Molteno implant in intractable glaucoma. Eye 1988 ;2(Pt 3) : Freedman J, Rubin B. Molteno implants as a treatment for refractory glaucoma in black patients. Arch Ophthalmol 1991 ;109(10): Ancker E, Molteno AC. Molteno drainage implant for neovascular glaucoma. Trans Ophthalmol Soc U K 1982 ;102(Pt 1) : Faghihi H, Pars plana Ahmed valve implant and vitrectomy in the management of neovascular glaucoma. Ophthalmic Surg Lasers Imaging 2007 ;38(4): Chalam KV, Pars plana modified Baerveldt implant versus neodymium:yag cyclophotocoagulation in the Giaconi_49.indd Chap8 5/11/2009 1:32:50 PM

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