Ординатура / Офтальмология / Английские материалы / Essentials in Ophthalmology Glaucoma_Grehn, Stamper_2008

50 6 Uveitic Glaucoma

associated with increased IOP were active inflammation, steroid usage, increasing age, and number of years since diagnosis.

Duration of uveitis has been shown to play a role in

6the development of OHT and secondary glaucoma. In the review of Panek et al., OHT was observed in 26% of eyes

with chronic uveitis and 12% with acute disease [8]. Neri et al. reviewed the records of 391 patients with uveitis, and found the incidence of glaucoma (defined as IOP > 21 or glaucomatous optic nerve damage requiring medical and/ or surgical antiglaucoma treatment) after acute uveitis to be 7.6% at both three and twelve months [6]. In patients with chronic uveitis, the incidence of glaucoma at one and five years was 6.5 and 11.1% respectively, increasing to 22.3% after ten years [6]. Herbert et al. looked at the prevalence of OHT (defined as IOP > 21mmHg on two separate occasions) in 257 patients with uveitis seen over a three-month period. OHT was found in 26% of eyes with acute uveitis and 46.1% of eyes with chronic uveitis, with 15.1 and 33.8% requiring treatment. In addition to chronicity, other risk factors associated with increased IOP were active inflammation, steroid usage, increasing age, and number of years since diagnosis. Severity of disease, as quantified through the presence of posterior synechiae, has also been associated with increased prevalence of secondary glaucoma [6, 10]. Anterior uveitis is most commonly associated with OHT and secondary glaucoma [3, 5].

Summary for the Clinician

■OHT is more commonly associated with uveitis than secondary glaucoma with optic nerve and visual field changes

■The duration and severity of uveitis are associated with an increased frequency of OHT and secondary glaucoma

6.3Pathogenesis of Uveitic Glaucoma

6.3.1Aqueous Dynamics in Uveitic Glaucoma

Maintenance of normal intraocular pressure is a delicate balance between aqueous humor production and outflow. In iridocyclitis, the inflamed ciliary body usually produces less aqueous humor. If outflow remains the same, the intraocular pressure will be decreased. Outflow may also be increased, exacerbating hypotony from ciliary body inflammation [11].

However, with an open angle, if there is an obstruction to outflow, intraocular pressure may be elevated.

Inflammatory cells, protein and fibrin from a disrupted blood–aqueous barrier can accumulate in the trabecular meshwork, resulting in the obstruction of aqueous outflow [12]. This can be a transient occurrence, but over time, may lead to irreversible damage [2]. Precipitates on the trabecular meshwork can obstruct outflow [13]. Swelling or dysfunction of the endothelium or trabecular lamellae can also result in decreased outflow [14]. Chronic mechanisms of outflow obstruction include scarring and obliteration of the trabecular meshwork or Schlemm’s canal, loss or dysfunction of trabecular endothelial cells, or the overgrowth of an endothe- lial–cuticular or fibrovascular membrane in the open angle, which may contract, resulting in closure of the angle [1, 2].

It has been suggested that a low perfusion rate may damage the trabecular meshwork. Johnson has shown that a perfusion rate of less than 1 microliter per minute may affect the functioning of the trabecular meshwork [15]. Thus, inflammation of the ciliary body and subsequent decreased aqueous production may lead to decreased perfusion and damage to the trabecular meshwork [16].

Biochemical changes in the aqueous humor of eyes with uveitis can cause IOP elevation by mediating aqueous production and obstructing aqueous outflow [2]. In experimental autoimmune uveitis, inflammatory cells can infiltrate and destroy the trabecular meshwork [17, 18]. They can also be directly cytotoxic to the surrounding tissue and liberate substances such as oxygen free radicals and proteolytic enzymes [17]. Cytokines may increase the IOP in uveitic eyes by increasing the inflammation, by stimulating neovascularization, and by having a direct effect on aqueous humor dynamics [19]. Cytokines may also have a direct effect on the TM cell population, either through a direct cytotoxic effect, or by stimulating cell migration away from the TM [20].

6.3.2Mechanical Causes of Uveitic Glaucoma

Acute angle closure can occur through several mechanisms. Iridocyclitis, annular choroidal detachment, and posterior scleritis can cause inflammation and edema, leading to forward rotation of the ciliary body and acute angle closure [2]. Pars planitis and uveal effusion can cause choroidal and ciliary body detachment with subsequent angle closure [2]. Massive exudative retinal detachment can displace the lens–iris diaphragm anteriorly, resulting in angle closure [1].

In patients with anterior uveitis, adhesions can develop between the posterior surface of the iris and the anterior

lens capsule, the vitreous face in aphakic patients, a sulcus or posterior chamber intraocular lens, or the residual capsule in pseudophakic patients [2]. These posterior synechiae can cause pupillary block by impeding the flow of aqueous between the posterior and anterior chamber [2]. This leads to iris bombé and closure of the anterior chamber angle [2]. Posterior synechiae occur more commonly in granulomatous than nongranulomatous disease [2].

In chronic inflammation, neovascularization, iris bombé, or peripheral anterior synechiae (PAS) may develop and result in closure of the angle [2]. It is believed that exudates and transudates from incompetent blood vessels in the setting of narrow angles may lead to PAS formation. These are usually broad bands attaching to the anterior trabeculum and even the cornea, and are more common in granulomatous conditions [2]. Although in some cases the anterior portion of the trabeculum may be visible on gonioscopy, the trabeculum may still be functionally closed [2]. In eyes that have less than 360° of PAS, the remainder of the angle may be compromised by the presence of pigment [2].

6.3.3Steroid-Induced Glaucoma

Treatment of uveitis with corticosteroids can result in increased ocular pressure, and if not managed appropriately, in optic nerve damage. This condition is known as steroid-induced glaucoma, and occurs more frequently in people who have chronic open-angle glaucoma (COAG) or a family history of this disease [1]. Other risk factors include high myopia, type II diabetes mellitus, and connective tissue diseases [2]. As in COAG, the angle is usually open and there are no symptoms [1]. Increased intraocular pressure can occur within weeks (approximately two weeks) with more potent steroids, and within months with weaker steroids [1]. However, acute pressure rises can also occur [21]. Topical corticosteroid therapy is more often associated with a rise in intraocular pressure than systemic administration [1]. Periocular and intravitreal steroids can also cause elevations in IOP that may be more difficult to deal with given their longer-acting effects. Inhalational and nasal steroids have also been reported to cause increases in IOP [1].

It is thought that the rise in intraocular pressure from corticosteroid use is due to a decrease in outflow [1, 2]. Animal studies have shown that trabecular and anterior uveal tissues have a high concentration of glucocorticoid receptors and are most likely the tissues affected by glucocorticoids to decrease outflow [22, 23]. Corticosteroids may cause polymerized glycosaminoglycans to accumulate and block the trabecular meshwork [24,

25]. Other studies have shown that dexamethasone can decrease the synthesis of collagen and the activity of tissue plasminogen activator [26, 27]. In cultured human trabecular meshwork cells, glucocorticoids increased the expression of the extracellular matrix protein fibronectin, which is seen in patients with COAG, and caused the formation of a crosslinked actin network in the trabecular meshwork cytoskeleton [28, 29]. It has also been hypothesized that corticosteroids may suppress the phagocytic activity of the trabecular endothelium, thus allowing the accumulation of debris which blocks outflow [1, 2]. Inhibition of the synthesis of PGE2 and PGF2a, which increase outflow facility, may also increase IOP [30]. Genetic influences may play a role in steroid-induced intraocular pressure elevation. For example, glucocorticoids induce the expression of myocilin mRNA, which is a protein involved in TM outflow resistance [16].

Summary for the Clinician

■A wide range of factors are associated with the development of OHT and secondary glaucoma from uveitis

■Clinical evaluation can help in determining whether mechanical obstruction is the cause of elevated intraocular pressure

■IOP must be carefully monitored when using any form of corticosteroids in uveitic patients, since IOP rises can be dramatic

6.4Common Uveitic Entities Associated with OHT and Secondary Glaucoma

While any uveitic entity can cause an increase in intraocular pressure if the inflammation is not adequately controlled through the mechanisms previously discussed, there are certain entities that are more strongly associated with OHT and secondary glaucoma (Table 6.1). These will be discussed below.

6.4.1Glaucomatocyclitic Crisis: Posner–Schlossman Syndrome

Described in 1948 by Posner and Schlossman, this is a monocular disease affecting young to middle-aged adults that is characterized by recurrent attacks of mild anterior uveitis with marked elevations in intraocular pressure [31]. Typical symptoms include slight ocular

Traumatic

Idiopathic

Lens-induced glaucoma (phacolytic, phacoanaphylactic, pseudophakic inflammatory glaucoma)

Other infectious diseases (mumps, rubella, Hansen’s disease)

discomfort, blurred vision and halos, lasting several hours to a few weeks, and recurring monthly or yearly [31]. On examination, mild inflammation is seen in the anterior chamber with a few small, discrete, round keratic precipitates that usually resolve spontaneously in several weeks. Keratic precipitates may also be seen on the trabecular meshwork, and corneal edema may be present due to the markedly elevated intraocular pressure, usually in the 40–50 mm Hg range. The IOP returns to normal in-between episodes of inflammation, but a chronic secondary glaucoma can develop which results in visual loss. The etiology of this disease is unknown, but associations include HLA-Bw54, herpetic viral infection, increased aqueous production due to elevated levels of prostaglandins, and chronic open-angle glaucoma [32– 34]. Most attacks can be controlled with corticosteroids and antiglaucoma medications.

6.4.2Fuchs’ Heterochromic Iridocyclitis

Fuchs’ heterochromic iridocyclitis is a relatively mild, chronic form of iridocyclitis associated with elevated intraocular pressure. Its characteristic feature is iris

Tuberculosis

Onchocerciasis

heterochromia, although this may be very mild or absent [35]. Usually only one eye is affected, although both eyes can be involved [35]. Typically, a low-grade anterior chamber reaction with small, stellate, keratic precipitates involving the entire corneal endothelium is seen [35]. The iris typically has extensive stromal atrophy with transillumination defects, and iris nodules may be present [35]. Posterior synechiae are generally absent [35]. Affected individuals develop posterior subcapsular cataracts [35]. The angle is typically open and free of synechiae, but fine, bridging vessels that cross the trabecular meshwork can cause bleeding during cataract surgery [35]. Vitreous opacities and chorioretinal scars may also be seen [35]. Although the etiology remains unknown, associations include infections with toxoplasma, toxocara, previous trauma, retinitis pigmentosa, elevated IgG levels, and autoantibodies directed against the cornea [35]. More recently, there has been convincing data linking rubella to Fuchs’ iridocyclitis [36–38].

Corticosteroids are generally ineffective in treating the inflammation, distinguishing this syndrome from glaucomatocyclitic crisis. In addition, intraocular pressure elevation is not as common as in Posner–Schlossman syndrome; the incidence varies from 15 to 59% [35].

However, the IOP is generally out of proportion to the mild amount of inflammation, and patients can have large fluctuations in IOP. Close follow-up and monitoring is recommended to detect the progression of glaucoma, and aggressive medical and surgical treatment is warranted if found [35]. A high proportion of patients do not respond to medical therapy, necessitating surgical treatment [35].

Treatment includes oral antivirals (acyclovir, famciclovir, and valacyclovir for HSV and VZV; and valganciclovir for CMV), topical corticosteroids and cycloplegic agents. IOP typically responds to control of the underlying inflammatory process, but glaucoma medications are typically prescribed initially to lower IOP. Approximately 12% of patients with keratouveitic glaucoma will develop persistent IOP elevation requiring chronic therapy [40].

6.4.3Herpetic Disease

The herpes family of viruses [herpes simplex (HSV), herpes zoster (HZV), and cytomegalovirus (CMV)] can cause a uveitis associated with elevated IOP [39–41]. Herpes simplex and zoster, however, are more commonly associated with a rise in IOP than CMV. Most commonly, the uveal inflammation is a keratouveitis secondary to corneal disease, and can present acutely, or run a chronic or recurrent course. A retrospective study by Falcon and Williams at the Moorfields Eye Hospital found OHT in 28% of 183 patients with HSV [40]. The majority had stromal keratitis or a metaherpetic ulcer [40]. Interestingly, none of the patients presented with increased IOP at the first manifestation of corneal disease [40].

Townsend and Kaufman looked at the pathogenesis of glaucoma secondary to HSV in rabbit eyes [42]. On histologic examination, a diffuse mononuclear cell infiltration was present in the iris root and trabecular meshwork with disruption of the lamellar arrangements [42]. All animals with persistent pressure elevations had anterior synechiae and 50% had retrocorneal membranes covering 180° of the angle circumference [42]. Endothelial cells showed swelling, vacuolization of the cytoplasm, loss of the normal compact arrangement, and large empty patches where necrotic cells had sloughed off without replacement [42]. These findings suggest that increased IOP in HSV keratouveitis is related to trabeculitis.

The pathophysiology of herpes zoster is thought to be similar to that of HSV-associated iridocyclitis. Secondary elevation of IOP and glaucoma occur in approximately 30% of cases, ranging from 16 to 56% [2, 43]. On clinical exam, diffuse, stellate, keratic precipitates covering the entire endothelium may be seen. Patchy or sectoral iris atrophy is characteristic of herpes infection. Retinitis and vasculitis may also occur.

CMV can also cause IOP elevation associated with an anterior uveitis in immunocompetent persons. The clinical appearance can mimic HSV and VZV, with diffuse keratic precipitates, iris atrophy with transillumination defects, and focal edema from endotheliitis. IOP can be severely elevated, up to 70 mmHg [41, 44, 45].

6.4.4Juvenile Inflammatory Arthritis (JIA)

JIA is a systemic disorder occurring in children classified into three major types based on age of onset and degree of articular and systemic involvement during the first three months. These include systemic onset (Still’s disease), polyarticular onset, and pauciarticular onset [2]. The latter type accounts for the majority of patients with uveitis, and is further characterized by the presence of ANA antibodies [2]. The incidence of uveitis in JIA ranges from 2 to 21% [2]. In about 80% of cases, ocular involvement is bilateral, and the iridocyclitis is usually mild, insidious, chronic, and asymptomatic [2]. It is typically nongranulomatous, although granulomatous signs such as mutton fat keratic precipitates and Koeppe nodules have been observed [2]. Complications include band keratopathy, cataract, posterior synechiae, macular edema, papillitis, and secondary glaucoma [2]. The incidence of glaucoma varies from 14 to 42%, and is most often caused by closure of the angle by peripheral anterior synechiae, although open angle glaucoma with trabecular obstruction and steroid induced glaucoma may also occur [2, 46–48]. Medical treatment can control the glaucoma in about 50% of patients, with only 30% controlled over the long term [2]. Surgical options include goniotomy, trabeculodialysis, filtration surgery with antimetabolites, and drainage device implants.

6.4.5Pars Planitis

Pars planitis refers to idiopathic inflammation of the anterior vitreous and pars plana. It is a diagnosis of exclusion after ruling out other causes of intermediate uveitis, such as sarcoidosis, Lyme disease, tuberculosis, syphilis, and multiple sclerosis. On presentation, patients may be asymptomatic or have floaters or decreased vision. The disease is often bilateral but often asymmetric. Clinically, snowbanking, snowballs, peripheral retinal periphlebitis, anterior vitreous cells, and vitreous opacities may be seen [2]. Complications include glaucoma, cataract, CME, band keratopathy, papillitis, vitreous hemorrhage, and

54 6 Uveitic Glaucoma

tractional and rhegmatogenous retinal detachment [2]. The incidence of glaucoma varies from 7 to 8%, and is as high as 15% in children [2].

Mechanisms of increased IOP and glaucoma include

6peripheral anterior synechiae (PAS), posterior synechiae with iris bombé, neovascular glaucoma, open-angle glau-

coma, and steroid-induced ocular hypertension [2].

6.4.6 Toxoplasmosis

Ocular toxoplasmosis is caused by an obligate intracellular parasitic protozoan, Toxoplasma gondii. Transmission can occur in utero or postnatally. Cats are the definitive hosts of the parasite, and oocysts shed in cat feces can remain viable in the environment for long periods of time [49]. Postnatal infections are due to ingestion of tissue cysts in raw or undercooked meat, ingestion of oocysts on unwashed vegetables that are contaminated with soil containing cat feces, or from contaminated drinking water [49]. Toxoplasmosis is the most common cause of posterior uveitis, accounting for 7–15% of all cases of uveitis. Toxoplasma causes a focal necrotizing retinochoroiditis, often adjacent to a chorioretinal scar, as well as vitritis and perivasculitis [50]. Granulomatous anterior uveitis, neuroretinitis, punctate outer retinitis, and scleritis can also occur [50]. Complications include rhegmatogenous and exudative retinal detachment, retinal vessel occlusions, subretinal neovascularization, epiretinal membrane formation, macular edema, and glaucoma [50].

The prevalence of OHT in toxoplasmosis ranges from 3 to 38% [51]. A recent retrospective review of 61 patients with toxoplasmosis retinochoroiditis found elevated IOP in 38% of patients, with a trend suggesting that an increased anterior chamber response may be related. The IOP elevation was usually transient, normalizing as the episode of chorioretinitis resolved. In 3.3% of patients, IOP elevation required chronic medication or surgical treatment [51].

6.4.7Sarcoidosis

Sarcoidosis is a multisystem inflammatory disorder of uncertain origin, characterized by noncaseating granulomas. It most commonly affects the lungs, eyes, and skin. It accounts for 3–7% of noninfectious uveitis cases, and ocular involvement is found in 20–30% of cases of systemic sarcoid [52, 53]. While sarcoidosis can affect any part of the eye, the most common ocular manifestation is anterior uveitis [2]. Mutton fat keratic

precipitates are characteristic, as are posterior synechiae and iris nodules [2]. Iris nodules may involve the pupillary border (Koeppe’s nodules), iris stroma (Busacca’s nodules), anterior chamber angle, and ciliary body [1, 2]. Posterior segment involvement includes periphlebitis with “candle wax drippings,” vitritis, choroidal granulomas, exudative retinal detachment, and optic nerve involvement [1, 2].

The incidence of glaucoma in sarcoid ranges from 10.9 to 25.5% [2]. Mechanisms of increased IOP and subsequent glaucoma include outflow obstruction by PAS, obstruction of the trabecular meshwork by inflammatory cells and nodules, neovascularization of the angle, and steroid-induced glaucoma [2]. Secondary glaucoma in uveitis associated with sarcoid is associated with poor visual outcomes; in one retrospective study of 60 patients with sarcoid-related uveitis, glaucoma was one of the risk factors associated with vision worse than 20/40 [53, 54].

6.4.8Syphilis

Increased intraocular pressure and subsequent glaucoma can be seen in both the congenital and the acquired forms of syphilis. The most common ocular finding is interstitial keratitis (IK), which typically appears between the age of 5 and 16 [2]. Anterior uveitis is often present as well [2]. Closed-angle glaucoma occurs as a result of posterior synechiae with iris bombé, PAS, uveal cysts, and lens subluxation or complete dislocation [2]. Patients with IK early in infancy may develop a narrow angle which can predispose them to angle closure [2]. Open-angle glaucoma may also occur [2].

A recent retrospective review of 39 patients with uveitis secondary to syphilis found increased IOP in 18% coincident with the onset of inflammation [9]. Potential mechanisms to account for the increased IOP include clogging of the trabecular meshwork with inflammatory debris and/or a prostaglandin-mediated increase in vascular permeability causing increased aqueous humor production [9].

Summary for the Clinician

■Many uveitic entities are associated with OHT and secondary glaucoma

■Posner–Schlossman syndrome and Fuchs’ heterochromic iridocyclitis can be distinguished by their responsiveness to topical corticosteroids

6.5 Treatment of Uveitic Glaucoma

6.5.1Medical Treatment

Topical medications are the first line agents to be used in the management of elevated IOP associated with uveitis. These include beta blockers which decrease aqueous production. It is worth noting that metipranolol has been associated with granulomatous iridocyclitis and therefore should be avoided in patients with uveitis [16]. Adren ergic agonists, carbonic anhydrase inhibitors (topical, intravenous and oral), and hyperosmotic agents may also be used to control IOP. Miotics should be avoided in uveitic glaucoma, as they may potentiate the formation of posterior synechiae or pupillary membranes, cause discomfort by aggravating ciliary muscle spasm, and increase inflammation by enhancing breakdown of the blood–aqueous barrier [2]. Prostaglandin analogs may also be used to reduce elevated IOP. However, there have been reports associating them with uveitis and cystoid macular edema due to breakdown of the blood–aqueous barrier, so they are generally used with caution [55–61]. Latanoprost should also be used with caution in patients with a history of herpetic disease, as it has been linked to disease recurrence [16].

If an increase in IOP is thought to be secondary to corticosteroid use, corticosteroids may be tapered or switched to drugs with less tendency to elevate the IOP, such as loteprednol, fluorometholone, or rimexolone. In rare cases, the elevated IOP may persist despite discontinuing steroids [1]. This is more common in chronic users of corticosteroids [1]. In cases where corticosteroids were injected subconjunctivally or under Tenon’s capsule, it may be possible to surgically remove the steroid depot [2].

In patients with severe noninfectious uveitis with elevated IOP secondary to steroid use, systemic immunomodulating agents should be considered for control of inflammation. These include antimetabolites (methotrexate, mycophenolate mofetil, azathioprine), alkylating agents (cyclophosphamide and chlorambucil), and T cell inhibitors (cyclosporine and tacrolimus) [62]. Newer agents include the biologics, which target molecules in the inflammatory cascade and include tumor necrosis factor (TNF) alpha inhibitors (infliximab, adalimumab), IL-2 inhibitors (daclizumab), and co-stimulatory molecule inhibitors (abatacept). While relatively new, these agents have shown promise in controlling noninfectious uveitis refractory to corticosteroids and the traditional immunomodulating agents listed above.

6.5.2Surgical Treatment

In cases of pupillary block causing closed-angle glaucoma, a laser iridotomy can be used to re-establish a pathway for aqueous outflow. The combination of a Nd-YAG laser with an argon laser may be more effective in creating an opening in patients with dark irides [2]. Postoperative inflammation is common in all patients, but may be especially severe in those patients with active uveitis or a prior history of uveitis, and may result in closure of the iridotomy site. Aggressive treatment with topical corticosteroids is recommended to reduce this complication. A surgical iridectomy can be performed when laser iridotomy is unsuccessful or cannot be performed. Post-op inflammation in these cases is generally more severe and may require the use of systemic corticosteroids in the perioperative period [2].

Other surgical procedures for closed-angle, openangle, and mixed-mechanism glaucoma include goniotomy, trabeculodialysis, cyclophotocoagulation, trabeculectomy, and drainage device implantation. Goniotomy and trabeculodialysis have been used in young patients with uveitic glaucoma with moderate success, with IOP control in patients ranging from 56 to 72% [63–66]. Trabeculectomy with adjuvant antimetabolite therapy have been reported to improve the outcome of filtering surgery vs. trabecul-ectomy alone [2]. Mitomycin C (MMC) may be preferable to 5-fluorouracil in uveitic patients, as it has been shown to lower IOP more and for a longer duration than 5-fluorouracil in high risk glaucoma surgery [16, 67]. Aqueous drainage devices such as Ahmed and Molteno valves have been developed in order to avoid fibrosis of the draining fistula, especially when significant postoperative inflammation is likely [2]. They should be considered in aphakic patients (particularly those with JIA-associated uveitis) and patients with previous trabeculectomy failures [16]. MMC is currently being used with aqueous drainage devices to achieve lower IOP and prevent postoperative bleb encapsulation [16]. Aggressive preoperative topical and systemic corticosteroids can help to reduce and control inflammation in preparation for surgery [16]. Alternatively, an infraorbital depot of 40 mg of methylprednisolone can be given at the conclusion of surgery [16]. Postoperative inflammation or reactivation of uveitis can occur and can be managed with preand post-operative corticosteroids, as well as steroid-sparing immunomodulatory therapy if necessary.

56 6 Uveitic Glaucoma

Summary for the Clinician

■Metipranolol and miotics should be avoided in patients with uveitis and glaucoma. Prostaglandin

6analogs should be used with care.

■Lower-strength topical corticosteroids may be substituted in cases of corticosteroid-induced OHT. Immunomodulating treatment may be considered when oral corticosteroids cannot be used.

■In cases of OHT and secondary glaucoma refractory to medical management, surgical options include trabeculectomy and aqueous drainage devices with antimetabolites.

6.6Conclusion

Ocular hypertension and subsequent secondary glaucoma are potentially blinding complications of uveitis. Although the pathophysiology is incompletely understood, damage to the outflow channels and mechanical obstruction are contributing factors. Corticosteroid use also plays a significant role in contributing to OHT in uveitic patients. Common entities associated with OHT and secondary glaucoma include Fuchs’ heterochromic iridocyclitis, Posner–Scholssman syndrome, viral infection, sarcoidosis, and syphilis. Treatment options include both medical and surgical therapy. The advent of biologic agents may further reduce the incidence of uveitic glaucoma by controlling refractory inflammation and by reducing chronic corticosteroid use.

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■Nonpenetrating glaucoma surgery (NPGS) refers to drainage procedures that restore aqueous humor filtration through a natural membrane, the trabeculo-Descemet’s membrane (TDM). It targets the presumed site of pathology, namely Schlemm’s canal and the juxtacanalicular meshwork.

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■The main advantage of NPGS is the prevention of early complications related to the penetration of

the anterior chamber. The main disadvantage is the long learning curve it demands.

■Its safety profile makes it the first choice in many cases. Primary and secondary angle-closure glaucomas are relative contraindications. Neovascular glaucoma is an absolute contraindication.

■NPGS is efficient at lowering the intraocular pressure. The use of space-occupying implants and Nd-YAG goniopuncture is associated with a higher success rate.

7.1Introduction

In 1964 Krasnov published his first report on sinusotomy. This operation consisted of removing a lamellar band of sclera and opening Schlemm’s canal over 120° from ten to two o’ clock [1]. The inner wall of Schlemm’s canal was untouched and the conjunctiva was closed. Sinusotomy never became popular because it was a difficult operation; it needed a surgical microscope, and Schlemm’s canal had to be found, which was not easy. In the late 1960s and for the next three decades, trabeculectomy, as described by Sugar [2] in 1961 and Cairns [3] in 1968 became the gold standard technique for filtering surgery. However, even with the numerous modifications proposed to the original trabeculectomy, the lack of a reproducible postoperative intraocular pressure (IOP) reduction as well as early postoperative complications, such as overfiltration and hypotony, mainly related to penetration of the anterior chamber with sudden decompression of the eye, led several surgeons to reconsider Kraznov’s work. Several techniques of nonpenetrating filtering surgery based on sinusotomy have been described. Since the main aqueous outflow resistance is located at the juxtacanalicular trabeculum and the inner wall of Schlemm’s canal, these two anatomical structures were targeted. Nonpenetrating trabeculectomy was proposed by Zimmermann [4]

in 1984, and Arenas first published the term ab-externo trabeculectomy in 1991 [5]. Fyodorov stressed the removal of the corneal stroma behind the anterior trabeculum and Descemet’s membrane, and termed this “deep sclerectomy” [6]. This was also described by Kozlov [7] and later by Stegmann [8]. Currently, deep sclerectomy, along with ab-externo trabeculectomy and viscocanalostomy, are the mostly commonly used nonpenetrating procedures.

7.2Deep Sclerectomy

7.2.1Superficial Scleral Flaps

The conjunctiva may be opened either at the fornix or at the limbus. A 5 × 5 mm superficial scleral flap is created that includes one-third of the scleral thickness (300 mm). To allow Descemet’s membrane to be reached later in the dissection, the superficial scleral flap must be cut 1–2 mm anteriorly into clear cornea (Fig. 7.1). The initial incision is made with a No. 11 stainless steel blade and the horizontal dissection with any crescent knife. In patients with a high risk of scleroconjunctival scar formation, a sponge soaked in mitomycine 0.02% may be placed for 45 s in the scleral bed and between the sclera and Tenon’s capsule, and then washed with balanced salt solution for 60 s.