Elevated intraocular pressure associated with retinal procedures

From EyeWiki


Introduction

Secondary glaucoma can occur after various vitreoretinal procedures[1] [2]. The risk factors vary for each type of procedure, and are of particular importance for the follow-up management of patients who may be predisposed to elevation of intraocular pressure (IOP). The pathophysiology can be either due to open-angle[1][3], closed-angle mechanisms[1][3][4], or both[1][3], which can heavily influence the management of secondary IOP elevation. This article provides a summary of the incidence, risk factors, pathophysiology, as well as management of elevated IOP following selected vitreous and retinal procedures.

Glaucoma following pars plana vitrectomy (PPV)

Incidence

Elevated IOP is a common complication following pars plana vitrectomy[3]. The reported frequency of post-vitrectomy glaucoma from studies done in 1970 and 1980s ranges from 20-60%[3][5] [6] [7]. In a prospective study, Han et al[3] found that approximately 60% of patients had an acute IOP rise of 5-22 mg Hg within 48 hours of PPV and approximately 36% of patients had an acute IOP rise of > 30 mmHg; there was no significant difference between preoperative and late postoperative IOP. In a recent retrospective cohort study of 111 eyes with a mean follow up of 49 months, there was no longterm increase in IOP following pars plana vitrectomy[8]

Risk factors

There are several variables that are associated with an increased risk of acute IOP elevation following pars plana vitrectomy; these include: combined scleral buckle and PPV, intraoperative scatter endophotocoagulation, and/or pars plana lensectomy performed at the same time as pars plana vitrectomy[3]. Fibrin formation after PPV also increases the risk of secondary glaucoma[3]. In addition, patients undergoing pars plana vitrectomy for proliferative vitreoretinopathy are more likely to experience postoperative IOP elevation compared to those undergoing the procedure for macular hole repair[3].

Pathophysiology

Secondary open-angle glaucoma (OAG) accounts for the majority of postvitrectomy glaucoma, with angle closure mechanisms accounting for approximately 20% of cases[3]. OAG is caused by: gas expansion without angle closure, inflammation, silicone oil without pupillary block, corticosteroid response, and blood-mediated mechanisms[4]. Angle closure mechanisms include pupillary block mediated by intraocular gas, silicone oil, fibrin or intraocular lens as well as ciliary body edema and iridocorneal apposition[3].

Management

The majority of patients without a previous history of ocular hypertension or glaucoma can tolerate a transient postoperative rise in IOP, with no evident effect on visual function[9]. If therapy is needed to control IOP elevation, most cases can be managed medically with antiglaucoma medications[1]. Occasionally, surgical intervention is needed to relieve extremely high IOPs, and the procedure is chosen carefully based on the mechanism of IOP elevation. Han et al.[3] showed that 11% of the patients in their study required some form of surgical intervention which included anterior chamber paracentesis, laser iridotomy, laser iridoplasty and laser membranectomy; none of their patients required a trabeculectomy or placement of glaucoma drainage device. In cases of postoperative fibrin pupillary block, argon laser has been used to create holes in the fibrin pupillary membrane[10], and intrecameral injection of recombinant tissue plasminogen activator has been successfully used to dissolve the fibrin clot[11].  

Glaucoma following scleral buckle procedure

Incidence

The occurrence of angle-closure glaucoma following scleral buckle is estimated to be 1.4% to 4.4%[12][13]. However, the incidence of shallowing of the anterior chamber without angle closure has been reported to be significantly higher, ranging from 14.4% to 50%[14].

Risk factors

Predisposing factors for angle closure glaucoma following scleral buckling procedures include pre-existing narrow angles, use of an encircling band, placement of encircling band anterior to the equator, high myopia, older patient age, and postoperative ciliochoroidal detachment[2].

Pathophysiology

The mechanism behind angle closure after scleral buckling has been shown experimentally in animal models. Placement of scleral buckle causes impaired venous drainage from the vortex veins, leading to congestion and swelling of the ciliary body[2]. The edematous ciliary body is displaced anteriorly about the sclera spur, and shifts the lens-iris diaphragm forward resulting in angle closure[2].

Management

In most cases, secondary angle-closure glaucoma resolves spontaneously within several weeks. Medical therapy includes cycloplegics, corticosteroids and aqueous suppressants[2]. Laser iridoplasty may be beneficial in cases refractory to medical treatment by opening the angle and facilitating aqueous outflow. Laser iridotomy, however, is rarely helpful because pupillary block is not the primary mechanism of angle closure following scleral buckling[2]. Trabeculectomy may be technically difficult due to conjunctival scarring from previous retinal surgery. In a retrospective study, Sidoti et al.[15] found that aqueous tube shunts achieved IOP control (defined as final IOP between 6-21 mmHg) in 85% of patients with a follow-up of 19.1-45.5 months.

Glaucoma following panretinal photocoagulation (PRP)

Incidence

Transient increases in intraocular pressure following PRP is quite common, with 32% to 94% of patients experiencing an increase in IOP of > 6 mm Hg[16] [17]. The IOP spikes usually occur immediately following retinal photocoagulation; in a study by Blondeau et al.[16], all cases of PRP-related ocular hypertension were detected within 2 hours after laser treatment.

Risk factors

The risk factors have not been well studied however it appears that the amount of laser energy may influence the incidence and severity of pressure elevations16.[16] Tsai et al.[16] hypothesized that lower laser energy levels may be associated with decreased incidence and severity of IOP elevation following PRP. In addition, neither age nor the type of diabetes influences the incidence[17].

Pathophysiology

IOP elevation after PRP may result from open or closed angle mechanisms.  Proposed open angle mechanisms include: aqueous outflow blockage due to compression of episcleral veins by the flanges of the fundus contact lens used in delivering the photocoagulation treatment; movement of fluid from choroid into the vitreous secondary to breakdown of blood-retinal barrier; decreased uveoscleral outflow from congestion of the ciliary body; laser damage to the short ciliary nerves causing decreased ciliary muscle tone, as well as release of prostaglandins[17]. The pathogenesis behind closed-angle is thought to be due to swelling of the ciliary body or movement of fluid from the choroid into the vitreous secondary to a temporary weakening of the blood-retinal barrier, both of which can lead to anterior displacement of lens-iris diaphragm[17]

Management

The IOP elevation is usually transient with most cases resolving within 1 month. Pretreatment with apralonidine has been shown to reduce the incidence of IOP elevation following laser surgery as compared to placebo (25% vs 32%), however the difference was not statistically significant[16]. IOP elevation following PRP can usually be managed medically by topical medications such as cycloplegics and aqueous suppressants.

Glaucoma following intravitreal anti vascular endothelial growth factor

Incidence

Use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents such as ranibizumab (Lucentis) and bevacizumab (Avastin) can lead to acute and/or chronic elevation of IOP. The incidence of sustained IOP elevations has been reported to range from 3.45% to 6%, and appears to be related the frequency of intravitreal anti-VEGF injections[18] [19][20].

Risk factors

The risk factors for ocular hypertension following intravitreal anti-VEGF have not been well documented. Good et al.[19] has found a higher prevalence of eyes with IOP elevations after receiving only bevacizumab (9.9%) as compared with those only receiving ranibizumab (3.1%), as well as higher prevelance in patients with preexisting glaucoma compared with eyes without preexisting glaucoma. In addition, the incidence of sustained IOP elevation appears to be related to the frequency of intravitreal anti-VEGF as lower frequencies of anti-VEGF treatment may reduce the risk of further IOP elevation[20].

Pathophysiology

The mechanism in which intravitreal anti-VEGF therapy contributes to IOP elevation is not clear; however there have been several proposed mechanisms. Immediate rise in IOP may be related to the volume of fluid introduced into the vitreous cavity via intravitreal injection. Anti-VEGF may directly obstruct aqueous outflow via the trabecular mechwork, the uveoscleral pathway or Schlemm canal[20]. The drug or byproducts of pharmacologic compounding or storage may physically block the outflow system or damage the cells of the trabecular meswork; and repeated intravitreal injection may lead to chronic inflammation or trabeculitis which could also contribute to sustained ocular hypertension[20].

Management

As the half life of intravitreal ranibizumab is approximately 3 days, the elevated IOP seen following intravitreal injection is usually transient[20]. Reducing the frequency of intravitreal anti-VEGF treatment by assessing treatment efficacy with OCT also appears to reduce the risk of sustained IOP elevation. In a recent study, Tseng et al.[20] reported on 19 eyes in which the IOP continued to rise during continued anti-VEGF therapy; antiglaucoma treatment included topical therapy (19 out of 19 patients), changing to OCT- guided "as needed" (PRN) dosing (6 out of 19 patients), laser trabeculoplasty (3 out of 19 patients), and glaucoma filtration surgery (5 out of 19 patients).

Glaucoma following intravitreal triamcinolone acetonide injection (IVTA):

Incidence

IVTA has been shown to have a high incidence of IOP elevation following a single intravitreal injection. Approximately 40% of patients can develop an IOP greater than 24 mm Hg at 6 months following 4 mg of IVTA injection[21].

Risk factors

There are several factors that may increase the risk for steroid-induced ocular hypertension. A review of the literature by Jones et al.[22] listed the following as predisposing risk factors: pre-existing primary open angle glaucoma or ocular hypertension; a family history of glaucoma in a first-degree relative; age (which appears to have a bimodal distribution peaking at age 6 and old age at the highest risk); connective tissue disease; type-1 diabetes; and high myopia.

Pathophysiology

Corticosteroids induce ocular hypertension by increasing the resistance of aqueous outflow through several mechanisms. Jones et al.[22] have summarized these mechanisms into three categories:  induced physical and mechanical changes in the microstructure of the trabecular meshwork thus impeding outflow of aqueous humor; increased deposition of substances in the trabecular meshwork which reduces outflow; decreased breakdown of substances in the trabecular meshwork by inhibiting proteases and trabecular meshwork endothelial cell phagocytosis. These three mechanisms act together to increase aqueous outflow resistance, thereby increasing IOP.

Management

Following intravitreal injection of triamcinolone acetonide, patients should be followed closely, especially those with risk factors. Jones et al.[22] suggest that patients with high risk of developing glaucoma should have their IOP checked 1 day post-injection, 1 week post-injection and 6 months thereafter, though others advocate for more frequent follow up. Initial management includes discontinuing steroid use if possible and initiating glaucoma medications. One study suggested that triamcinolone induced IOP elevation may last up to 9 months or longer after an intravitreal injection[23]; therefore the risks of IOP elevation must be considered seriously before IVTA use in high-risk patients.  Treatment with antiglaucoma medications is usually sufficient in controlling IOP;   in the majority of patients, IOP returns to baseline and glaucoma medications can be discontinued within 6 months from the time of injection[24]. Agrawal, et al. found that trabeculectomy is needed to control IOP in less than 2% of cases;  both standard trabeculectomy as well as trabeculectomy combined with vitrectomy to remove intravitreal  traimcinolone acetonide  have been shown to be successful in controlling IOP[25].

Glaucoma following use of silicone oil

Incidence

Secondary glaucoma is a known complication of the use of silicone oil tampanode in the treatment of complicated retinal detachment. The incidence varies widely among studies, ranging from 2.2% to 56%, with recent studies demonstrating a lower prevalence than previously reported[26] [27]. However, most studies agree that a high percentage of patients do have a secondary IOP elevation that is often mild and transient, with a small percentage of patients developing chronic glaucoma.

Risk factors

Although the risk factors for development of IOP elevation remain unclear, several prognostic factors have been evaluated by a number of studies. Risk factors include pre-existing glaucoma, history of diabetes mellitus, and aphakia[2]. Among patients with CMV retinitis, the incidence of elevated IOP is rare, which is attributed to the diminished inflammatory response due to the underlying immune-compromised state. The quantity of emulsified silicone oil in the anterior chamber as well as the use of heavy tamponade agents has been shown to be associated with a significant IOP rise postoperatively[4].

Pathophysiology

There are several proposed mechanisms of silicone oil related glaucoma which may be divided into two groups: early postoperative IOP elevation and late-onset glaucoma. The mechanisms of early IOP rise may be due to pupillary block, inflammation, pre-existing glaucoma, and/or migration of silicone oil into the anterior chamber with resulting mechanical impediment to filtration. Possible mechanisms of late-onset glaucoma are infiltration of the trabecular meshwork by silicone bubbles, chronic inflammation, synechial angle closure, rubeosis iridis, migration of emulsified and nonemulsified silicone oil into the anterior chamber, and/or idiopathic open angle glaucoma4.

Management

Treatment of silicone oil associated glaucoma depends largely on the clinical presentation and the mechanism of IOP elevation. Management may include topical medications alone or in conjunction with surgical and/or laser interventions. Topical medical therapy including cycloplegics, corticosteroids, beta-blockers and prostaglandin analogues has been shown to result in successful control of IOP in 30-78% of patients[27][28]. Prophylactic peripheral iridectomy at the 6-o’clock position has lowered the incidence of pupillary block caused by floating silicone oil. However, peripheral iridectomies may close in up to 11-32% of cases and need to be reopened or a new iridotomy created to prevent the development of pupil block[4]. Transcleral cyclophotocoagulation may be an option when the risk of redetachment with silicone oil removal is unacceptable, or in eyes with poor visual potential due to its risk of visual loss. Early silicone oil removal may result in improvement in IOP control by reversing mechanical trabecular blockage; however silicone oil removal must be weighed against the risk of retinal detachment. One study has shown that 93.4% of patients had normalization of IOP after removal of silicone oil tamponade, whereas another study reported that elevated IOP persisted in all eyes even after silicone oil removal[29] [30]. A persistent IOP rise after silicone oil removal is thought to be due to inflammation and edema of the trabecular meshwork, as well as the obstruction of meshwork by small silicone oil droplets4. Glaucoma surgery and drainage devices may be considered in patients with refractory glaucoma, as well as patients with complete synechial angle closure since silicone oil removal alone is unlikely to be beneficial in these cases. However, standard filtration surgery may be technically difficult due to scarring of the conjunctiva from prior retinal surgery, and is associated with a poor prognosis and increased risk of complications. An inferiorly placed glaucoma drainage implant may be a useful alternative; in one study, the success rate of inferotemporally placed Ahmed glaucoma shunts was 86% at 6 months and 76% at one year after implantation[28].

Glaucoma following intravitreal gas

Incidence

Intraocular gases, specifically sulfur hexafluoride (SF6) and perflouropropane (C3F8), are frequently used for retinal tamponade due to their innate properties; they are expansile and have a long resorption time, which provides greater surface tension and allows more time for choroidal-retinal adhesions. However, these properties may also result in IOP elevation.[31] The incidence of IOP rise following intravitreal SF6 and C3F8 injection has been estimated to range from 6.1% to 67%, and 18% to 59%, respectively[32] [33] [34]. The higher incidence associated with C3F8 is thought to be related to its greater maximal volume expansion (4 times maximal volume expansion for C3F8 compared to 2 times maximal volume expansion for SF6), as well as longer intraocular longevity (55-65 days for C3F8 compared to 10-14 days for SF6)[2].

Risk factors

There are several variables associated with IOP elevation; higher concentrations of the expansile gas, use of C3F8, older patient age, intraoperative use of photocoagulation, concurrent lensectomy or placement of circumferential scleral buckle, and fibrinous anterior chamber exudates[1].

Pathophysiology

Secondary glaucoma following intravitreal gas injection may be due to both open-angle and closed-angle mechanisms. Open-angle mechanisms occur when expansion of the intraocular gas bubble exceeds the rate of outflow of intraocular fluid, or when the intraocular gas volume causes posterior chamber pressure build-up without angle-closure. Secondary closed-angle glaucoma results from anterior displacement of the lens-iris diaphragm causing iridocorneal apposition as a result of either pupillary block or non-pupillary block mechanisms[1][3].

Management

Intraocular pressure should be assessed by using the Goldmann applanation tonometer or Perkins tonometer. Pneumatic tonometers and high displacement tonometers may significantly underestimate the IOP due to compressibility of the intraocular gas[1]. Patient education is an essential part of management following intravitreal gas injection. The importance of maintaining a prone position must be emphasized to prevent anterior displacement of the lens-iris diaphragm. In addition, the patient should be told to abstain from air travel until complete intraocular gas bubble resorption due to rapid expansion of the intravitreal gas volume with diminished atmospheric pressure. Elevations in IOP usually occur within the first 24 hours, and mild elevations in IOP frequently respond to topical aqueous suppressants or oral carbonic anhydrase inhibitors within 24 to 72 hours. If IOP rise is severe, it may be necessary to aspirate a potion of the intraocular gas to normalize IOP. Similar to silicone oil associated glaucoma, laser iridotomy may be beneficial in cases of pupillary block, and glaucoma drainage implantation may be a better surgical option compared to traditional filtering surgery if there is extensive to conjunctival scarring[1][2].

Conclusion

Secondary glaucoma is a well known complication following various retinal procedures. The mechanism can be open angle, closed angle or both. Most cases of secondary glaucoma can be management medically, with a small proportion of patients requiring laser and/or surgical intervention to achieve IOP control.

References:

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Costarides AP, Alabata P, Bergstrom C. Elevated intraocular pressure following vitreoretinal surgery. Ophthalmol Clin N Am. 2004; 17(4):507-512.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Gedde SJ. Management of glaucoma after retinal detachment surgery. Curr Opin Ophthalmol. 2002;13(2):103-9.
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 Han DP, Lewis H, Lambrou FH Jr, et al. Mechanisms of intraocular pressure elevation after pars plana vitrectomy. Ophthalmology. 1989;96:1357.
  4. 4.0 4.1 4.2 4.3 Ichhpujani P, Jindal A, Katz JL. Silicone oil induced glaucoma: a review. Graefes Arch Clin Exp Ophthalmol. 2009;247(12):1585-1593.
  5. Faulborn J, Conway BP, Machemer R. Surgical complications of pars plana vitreous surgery. Ophthalmology. 1978;85:116.
  6. Aaberg TM, Van Horn DL. Late complications of pars plana vitreous surgery. Ophthalmology. 1978:85:126
  7. Ghartey KN, Teolentine FI, Freeman HM, et al. Close vitreous surgery. XVII. Results and complications of pars plana vitrectomy. Arch Ophthalmol. 1980:98:1248.
  8. Lalezary M, Kim SJ, Jiramongkolchai K, Recchia FM, Agarwal A, Sternberg P Jr. Long-term trends in intraocular pressure after pars plana vitrectomy. Retina. 2011;31(4):679-685.
  9. Tranos P, Bhar G, Little B. Postoperative intraocular pressure spikes: the need to treat. Eye(Lond). 2004; 18(7):673-9.
  10. Lewis H, Han D, Wiliams GA. Management of fibrin papillary-block glaucoma after pars plana vitrectomy with intravitreal gas injection. Am J Opthalmol. 1987;103:180.
  11. Jaffe GJ, Lewis H, Han DP, et al. Treatment of postvitrectomy fibrin papillary block with tissue plasminogen activator. Am J Ophthalmol. 1989;108:170.
  12. Sebestyen JG, Schepens CL, Rosenthal ML. Retinal detachment and glaucoma. I. Tonometric and gonioscopic study of 160 cases. Arch Ophthalmol. 1962;67:736-745.
  13. Perez RN, Phelps CD, Burton TC. Angle-closure glaucoma following scleral buckling operations. Trans Am Acad Ophthalmol Otolaryngol. 1976;81:247-252.
  14. Hartley RE, Marsh RJ. Anterior chamber depth changes after retinal detachment. Br J Opthalmol. 1973;57:546-550.
  15. Sidoti PA, Minckler DS, Baerveldt G, et al. Aqueous tube shunt to a pre-existing episcleral encircling element in the treatment of complicated glaucomas. Ophthalmology. 1994;101:1036-1043.
  16. 16.0 16.1 16.2 16.3 16.4 Tsai JC, Lee MB, WuDunn D, Dacey MP, Choi JC, Minckler DS. Incidence of Acute intraocular pressure elevation after panretinal photocoagulation. J Glaucoma. 1995;4(1):45-8.
  17. 17.0 17.1 17.2 17.3 Blondeau P, Pavan PR, Phelps CD. Acute pressure elevation following panretinal photocoagulation. Arch Ophthalmol. 1981;99(7):1239-41.
  18. Adelman RA, Zheng Q, Mayer HR. Persistent ocular hypertension following intravitreal bevacizumab and ranibizumab injections. J Ocul Pharmacol Ther. 2010;26:105-110.
  19. 19.0 19.1 Good TJ, Kimura AE, Wong LJ, et al. Sustained elevation of intraocular pressure after intravitreal injections of anti-VEGF agents. Br J Ophthalmol. 2010;95(8): 1111-4.
  20. 20.0 20.1 20.2 20.3 20.4 20.5 Tseng JJ, Vance SK, Della Torre KE, Mendonca LS, Cooney MJ, Klancnik JM, Sorenson JA, Freund KB. Sustained increased intraocular pressure related to intravitreal antivascular endothelial growth factor therapy for neovascular age-related macular degeneration. J Glaucoma. 2011;00:000-000. Accessed July 17, 2011. doi: 10.1097/IJG.0b013e31820d7d19.
  21. Smithen LM, Ober MD, Maranan L, Spaide RF. Intravitreal triamcinolone acetonide and intraocular pressure. Am J Ophthalmol. 2004;138:740-743.
  22. 22.0 22.1 22.2 Jones R 3rd, Rhee DJ. Corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature. Curr Opin Ophthalmol. 2006;17(2):163-7.
  23. Jonas JB, Kreissig I, Degenring R. Secondary chronic open-angle glaucoma after intravitreal triamcinolone acetonide. Arch Ophthalmol. 2003;121:729-730.
  24. Jonas JB, Degenrigh RF, Kreissig I, et al. Intraocular pressure elevation after intravitreal triamcinolone acetonide injection. Ophthalmology. 2005;112:593-598.
  25. Agrawal S, Agrawal J, Agrawal T. Management of intractable glaucoma following intravitreal triamcinolone acetonide. Am J Ophthalmol. 2004;138:286-287.
  26. De Corral LR, Cohen SB, Peyman GA. Effect of intravitreal silicone oil on intraocular pressure. Ophthalmic Surg. 1987;18:446-449.
  27. 27.0 27.1 Honavar SG, Goyal M, Majji AB et al. Glaucoma after pars plana vitrectomy and silicone oil injection for complicated retinal detachments. Ophthalmology. 1999; 10:169-167.
  28. 28.0 28.1 Al-Jazzaf AM, Netland PA, Chales S. Incidence and management of elevated intraocular pressure after silicone oil injection. J Glaucoma. 2005;14(1):40-46.
  29. Jonas JB, Knorr HL, Rank RM, Budde WM. Intraocular pressure and silicone oil endotamponade. J Glaucoma. 2001;10:102-108.
  30. Flaxel CJ, Mitchell SM, Aylward GW. Visual outcome after silicone oil removal and recurrent retinal detachment repair. Eye. 2000;14:834-838.
  31. Abrams GW, Swanson DE, Sabates WI. The results of sulfur hexaflouride gas in vitreous surgery. Am J Ophthalmol. 1982;94:165-171
  32. The Silicone Study Group. Vitrectomy with silicone oil or sulfur hexafluoride gas in eyes with severe proliferative vitreoretinopathy: Results of a randomized clinical trial. Silicone Study Report 1. Arch Ophthalmol. 1992;110:770-779.
  33. Chang S, Lincoff HA, Coleman D, et al. Perflourocarbon gases in vitreous surgery. Ophthalmology. 1985;92:651-656.
  34. The Silicone Study Group. Vitrectomy with silicone oil or perflouropropane gas in eyes with severe proliferative vitreoretinopathy: Results of a randomized clinical trial. Silicone Study Report 2. Arch Ophthalmol. 1992;110:780-792.