Ординатура / Офтальмология / Английские материалы / Pediatric Ophthalmology Current Thought and A Practical Guide_Wilson, Saunders, Trivedi_2008

cleavage syndrome, consists of a posterior defect in Descemet’s membrane associated with an opacity in that area with variable attachment of the iris to the periphery of the corneal leukoma (Fig. 24.9). Lens involvement is common in this condition, with cataract and/or lens adherence to the posterior corneal defect. Angle abnormalities often accompany Peters anomaly, with glaucoma incidence at least 50%. Although often occurring as an isolated ocular disorder, a wide range of associated systemic and other ocular anomalies have been reported with Peters anomaly, leading some to consider this a morphologic finding rather than a distinct entity [57]. Nonetheless, Peters anomaly can be caused by mutation in the PAX6 gene, the PITX2 gene, the CYP1B1 gene, or the FOXC1 gene [84c].

Glaucoma management in Peters anomaly, rendered difficult by the presence of corneal opacity, cataract, and shallow or absent anterior chamber, should begin with medication when angle surgery is not feasible. Surgical intervention usually includes aqueous drainage device implantation or judicious cycloablation; repeat glaucoma interventions are the rule. Corneal transplant should be avoided in favor of optical iridectomy in cases where a visual axis can be secured around a partial corneal opacity [42, 129, 130]. Phthisis and retinal detachment may result from a variety of mechanisms in these small, complex eyes.

Fig. 24.9  Peters anomaly in the right eye of an infant during examination under anesthesia. Glaucoma was managed with medications in this eye (the fellow eye was more severely affected and required surgery), and the vision corrects to 20/400

24.6.3.5Posterior Polymorphous Dystrophy

This autosomal dominant condition includes bilateral defects of the cornea at the level of Descemet’s membrane with corneal opacification and variable iridocorneal adhesions, and may be mild or severe in visual consequence. Glaucoma occurs in about 15% of individuals with posterior polymorphous dystrophy; the disorder has been mapped to locus 20p11.2-q11.2

[84d].

24.6.4Primary Pediatric Glaucoma Associated with Systemic Diseases

Primary glaucoma in children may be seen in association with certain systemic diseases in which ocular abnormalities are included in the syndrome complex (Table 24.1). A few of the clinical entities are briefly presented. See also those conditions (e.g., A-R and aniridia) listed above in Sect. 24.6.3.

24.6.4.1Phacomatoses

Sturge-Weber Syndrome

The most common of the phacomatoses, Sturge-We- ber syndrome (encephalotrigeminal angiomatosis), is a sporadic condition characterized by a congenital facial cutaneous angioma (port wine stain, nevus flammeus) affecting the facial areas innervated by the 1st and 2nd divisions of the trigeminal nerve (Fig. 24.10). Intracranial involvement may be complicated by epilepsy, paralysis, and visual field defects. Choroidal hemangiomas are present in 40% of cases, and 90% of these develop glaucoma, on the same side as the facial lesion (Figs. 24.11, 24.12a, b). Glaucoma may present at birth (goniodysgenesis suspected), but more often is acquired in childhood (the result of elevated episcleral venous pressure) [92].

Affected eyes usually demonstrate marked conjunctival and episcleral vascular prominence; gonioscopy usually reveals minor angle anatomic changes, often

Fig. 24.10  This 18-year-old man has a port wine stain involving the right upper lid and periorbital area, associated with glaucoma in the right eye (so-called Sturge-Weber glaucoma). See also Figs. 24.11 and 24.12

Fig. 24.11  Closer view of right eye in Sturge-Weber glaucoma (same patient as in Fig. 24.10), showing the prominent vascular pattern on the conjunctiva and episclera

with blood visible in Schlemm’s canal; the iris may show increased pigmentation.

Congenital or infancy-onset glaucoma in SturgeWeber syndrome usually requires surgical intervention. Angle surgery, although typically less effective than in cases of PCG, may prove useful; IOP reduction has been reported with both trabeculotomy and with combined trabeculotomy–trabeculectomy for these cases [60, 81]. Medication is the first-line treatment for glaucoma presenting after infancy, with

aqueous suppressants the mainstay of therapy. While guarded trabeculectomy has been performed in these cases, success has also been reported with glaucoma implant surgery [19, 45], as well as with careful cycloablation [116]. Due to the presence of choroidal hemangioma in Sturge-Weber glaucoma cases, choroidal expansion and hemorrhage may complicate any intraocular surgery which rapidly decompresses the eye, either during or after the procedure.

Neurofibromatosis

This autosomal dominant systemic disease may rarely first present with congenital or infant-onset glaucoma and ectropion uvea, usually with ipsilateral plexiform neuroma of the upper eyelid, and often striking ocular enlargement of the glaucomatous eye [89]. Neurofibromatosis (NF-1) has been linked to the neurofibromin gene, located on 17q11.2 [84e]. Café au lait spots of the skin commonly appear by the end of the first year of life, with Lisch nodules on the iris usually occurring around puberty. Several possible mechanisms may explain the glaucoma in NF-1: direct effects on the normal angle development, secondary changes to the angle tissue, as well as angle closure by thickened ciliary body and choroid or directly by fibrovascular tissue [43]. Treating the glaucoma associated with NF-1 can be challenging, and should begin with medications, since angle surgery is unlikely to control IOP. Reasonable surgical options in the older child include filtration surgery, aqueous drainage device implantation, or cycloablation.

24.6.4.2Metabolic Disease

Lowe (Oculocerebrorenal) Syndrome

Children afflicted with this rare X-linked recessive disease (linked to locus Xq26.1) [73, 84f] usually have bilateral glaucoma and cataracts, as well as associated mental retardation, renal rickets, aminoaciduria, hypotonia, acidemia, and irritability. Additional ocular abnormalities of Lowe syndrome often include microphthalmia, strabismus, nystagmus, and iris atrophy with poorly dilating pupils (which complicate cataract removal). The angle resembles that of PCG, and rarely responds to goniosurgery. Medical control rarely proves adequate, requiring additional surgery in the form of aqueous drainage device implantation and cyclodestructive surgery in refractory cases [32, 122].

24.7 Secondary Childhood Glaucoma

Pediatric glaucoma may occur secondary to a wide variety of ophthalmic conditions (see Table 24.1).

While secondary glaucoma is a consequence of another eye disease rather than a primary disorder of the aqueous humor filtration mechanism, the true mechanism of glaucoma in some conditions may be both primary and secondary (see Sect. 24.6.3).

24.7.1 Trauma

Glaucoma associated with ocular trauma most often relates to an acute or secondary anterior chamber hemorrhage (hyphema). IOP elevation more commonly occurs several days following acute blunt trauma, and tends to accompany either rebleeding, or a very large initial hyphema; treatment with moderately frequent topical steroid, cycloplegics, and bedrest may decrease risk of rebleeding. Various regimens have been employed to diminish rebleeding, including antifibrinolytic agents (e.g., aminocaproic acid) and oral steroids, with variable success [38]. Children with sickle cell hemoglobinopathies are especially susceptible to optic nerve damage with moderate IOP elevation, and should be followed, as should all hyphema victims, with serial examination and IOP measurement. Initial treatment of elevated IOP with medications and gentle anterior chamber irrigation usually suffice, since IOP often normalizes after hyphema resolution. Eyes with angle recession deserve long-term follow-up, since the onset of chronic glaucoma may be delayed by years to decades.

24.7.2 Neoplasm

Neoplasms rarely produce childhood glaucoma. Advanced retinoblastoma is the most common etiology of such glaucoma, usually due to neovascular glaucoma and angle dysfunction or closure, rather than to tumor cells in the anterior chamber. Medulloepithelioma, a neoplasm of the ciliary epithelium, can also induce secondary neovascular glaucoma.

Juvenile xanthogranuloma, a rare systemic disorder sometimes associated with histiocytic infiltration of the iris, can present with glaucoma from spontaneous hyphema or due to the accumulation of histiocytes blocking the trabecular meshwork. Although glaucoma medications, along with topical and sys-

temic steroids usually suffice, difficult cases may require surgical intervention, made challenging by the tendency for continued iris bleeding whenever the IOP is lowered.

24.7.3Inflammation and Steroidrelated Glaucoma

Glaucoma secondary to chronic inflammation often presents in association with chronic anterior uveitis (e.g., ANA-associated idiopathic uveitis or arthritis), and less often with other inflammatory conditions.

Glaucoma in these cases may occur by a variety of mechanisms, either acutely (e.g., trabeculitis, trabecular obstruction, iris bombe and pupillary block) or chronically (e.g., peripheral anterior synechiae, trabecular scarring/dysfunction, steroid-induced trabecular obstruction). Sometimes the diagnosis of uveitis-related glaucoma is delayed because steroid use is blamed for the IOP rise, but inflammation-re- lated aqueous outflow reduction masks the true glaucoma when the steroid use is reduced and the inflammation not well-controlled; judicious use of systemic steroid-sparing therapy is often critical to management of difficult cases, in conjunction with pediatric rheumatologists.

Managing glaucoma secondary to uveitis requires control of the underlying inflammation, followed initially by medical management, provided the anterior chamber angle remains open. Angle surgery often controls the IOP when medication is insufficient, but success is reduced in those eyes with extensive peripheral anterior synechiae, and after cataract removal

[41, 51]; tube implant surgery has also been reported quite successful in refractory cases [28, 128]. Cycloablation should be used with extreme caution in uveitic glaucoma, due to the risk of phthisis.

24.7.4 Lens-induced Glaucoma

Acute glaucoma with pupillary block and angle closure may develop in any child with ectopia lentis (from a variety of causes, e.g., homocystinuria, Weill-Marchesani syndrome, Marfan syndrome), due

to forward shifting of the lens into the pupillary aperture. Non-surgical treatment can sometimes break the angle closure attack, and involves some or all of the following: supine patient positioning, manual displacement of the lens posteriorly in the eye, medication with aqueous suppressants, mydriatics, and analgesics, and subsequent miotic use. Iridectomy helps prevent repeat elevated IOP but not anterior lens displacement, and lensectomy may ultimately be needed

(but is more safely performed with normalized IOP) [46].

24.7.5Aphakic (Pseudophakic) Glaucoma

Glaucoma occurs commonly after removal of congenital or developmental cataracts (reported incidence from 3% to 41%), and represents a serious cause of late visual loss in these eyes. The glaucoma, usually of the open-angle type and often asymptomatic, is often delayed in onset for many years following cataract removal (median onset 5 years) [33, 87]. Eyes having cataract removal earlier than 1 year of age, those with associated microphthalmia, and those with persistent fetal vasculature may be at higher risk for glaucoma development. Theories of pathogenesis in open-angle glaucoma after cataract removal include both mechanical (trabecular collapse due to loss of zonular tension on the scleral spur) and chemical (postoperative inflammatory trabecular damage and/ or vitreous-derived toxic factors), with no proof of either.

While peripheral iridectomy is mandatory and often curative in rare cases of angle-closure glaucoma after cataract removal, medical therapy is the first-line treatment in eyes with open angles (albeit with typical acquired angle abnormalities) [124].

Angle surgery is often disappointing in these cases, although 360-degree trabeculotomy sometimes temporizes in cases of early-onset glaucoma (personal experience). Trabeculectomy with antiproliferative agents should be used with extreme caution in aphakic or pseudophakic eyes, due to likelihood of bleb scarring and the high risk of endophthalmitis should postoperative bleb infection occur. Moderate success has been reported with aqueous drainage device sur-

gery, and cycloablation in selected refractory cases

[94]. Intraocular lens implantation, either primary or secondary, does not protect against glaucoma after cataract removal.

24.7.6 Miscellaneous Causes

Secondary glaucoma in children may occur after use of steroid eye drops (see Sect. 24.7.3), and as a complication of retinopathy of prematurity. Secondary glaucoma results rarely from prenatal rubella virus infection, and a variety of other reported causes (see Table 24.1). Although there is no consensus on the ideal treatment of rare causes of secondary glaucoma, determining the etiology in each case assists the clinician in planning reasonable treatment options.

24.8 Treatment

The treatment of pediatric glaucoma varies with the type of glaucoma present, although both medical therapy and surgery often are needed (Table 24.3). Early diagnosis and adequate IOP control, the goals of treatment, maximize visual function in children with glaucoma.

24.8.1 Medical Management

While surgical intervention is the definitive treatment for children with PCG and angle-closure glaucoma cases, medical therapy should be initiated for juvenile and aphakic open-angle glaucoma, as well as for most cases of secondary open-angle glaucoma. Long-term medical therapy, which frequently plays an important role in treating children with glaucoma, proves challenging. Among the difficulties encountered when using medications in children are ensuring adequate compliance, assessing drug-induced side effects, and the possible serious adverse systemic side effects of protracted therapy. Medications are best used judiciously, with care taken to discard those drugs not providing benefit, and periodic reassessment of the adequacy of IOP control (i.e., target pressure). Let us

briefly consider the five main glaucoma drug classes, and their particular application to treating pediatric glaucoma.

24.8.1.1Beta-adrenergic Antagonists (Beta Blockers)

As effective aqueous suppressants, topical beta blockers play an important role in the treatment of children with glaucoma. Well tolerated from an ocular point of view, these drugs can produce dangerous systemic side effects in infants (especially prematurely born) and in those children prone to bronchospasm (asthma) or cardiac problems [88]. When needed in small children, beta blockers should be used at low doses (e.g., timolol, or the relatively beta-1-selective betaxolol, both at 0.25%), with punctal occlusion when possible. Topical beta blockers play an important role in treating children with glaucoma, and are appropriate first-line drugs for many.

24.8.1.2Carbonic Anhydrase Inhibitors

Carbonic anhydrase inhibitors (CAIs) lower IOP(~20– 35%) by reducing aqueous production, and are available in both oral (primary acetazolamide/Diamox) and topical (dorzolamide/Trusopt and brinzolamide/ Azopt) forms. Acetazolamide lowers IOP more than its topical counterparts, is dosed at 10–20 mg/kg/day, and often produces metabolic acidosis and notable side effects that may include diarrhea, diminished energy levels, perioral and finger tingling, and loss of appetite and weight; it is therefore reserved for especially refractory cases, or those at high risk for surgical intervention. Topical dorzolamide or brinzolamide, each used b.i.d. or t.i.d., have minimal risk of systemic side effects, and serve as excellent secondline drugs in many children with glaucoma (and firstline in those unable to tolerate beta blockers).

24.8.1.3Miotics

Miotic drugs (cholinergic stimulators) have largely been supplanted by newer medications, in the treatment of both adults and children with glaucoma. Pilocarpine retains its usefulness to induce and maintain

miosis before and after goniotomy or trabeculotomy for congenital glaucoma. Stronger miotics such as echothiophate iodide (Phospholine Iodide) have also been useful in selected cases of aphakic glaucoma.

24.8.1.4Adrenergic Agonists

The topical alpha-2 agonist, brimonidine, while useful in older children with elevated IOP refractory to other medications, has produced life-threatening systemic side effects in infants (bradycardia, hypotension, hypothermia, hypotonia, and apnea), and severe somnolence in toddlers [36]. All children on brimonidine should be monitored for somnolence, and treated with the lowest effective dose (e.g., Alphagan P 0.1%). Apraclonidine (Iopidine 0.5%) helps

minimize bleeding with angle surgery, and may be better tolerated than brimonidine for selected younger children requiring lower IOP (personal unpublished data), especially those intolerant to beta blockers, or after corneal transplant to avoid topical carbonic anhydrase inhibitors.

24.8.1.5Prostaglandins

The prostaglandin analogues lower IOP mainly by enhancing uveoscleral aqueous outflow. Latanoprost has been shown to reduce IOP in some children with glaucoma, and may be especially useful in those with juvenile open-angle glaucoma [37]. Travoprost also reduces IOP in selected cases of pediatric glaucoma. While these drugs have an excellent systemic

safety profile, they do result in thick, dark, long eyelashes when used in children; iris color change has been reported in one child [18]. Excepting selected cases of juvenile open-angle glaucoma with beta blocker contraindications, prostaglandin-like agents are probably not yet appropriate first-line treatment for children.

24.8.2 Surgical Management

Surgical intervention is the indicated treatment for PCG, angle-closure glaucoma, and other cases of childhood glaucoma where medical therapy has failed to adequately control IOP. Although most experts recommend angle surgery initially to treat PCG, they often disagree regarding the optimal surgical algorithm for approaching refractory PCG and other pediatric glaucomas. Glaucoma surgery in children presents additional challenges to those encountered in adult surgery, often relating to the buphthalmic eye with stretched or distorted anatomy, and to the difficulties of postoperative evaluation and care in a young child; it is best undertaken by those with significant experience (Table 24.4). Since repeat surgery is not infrequently needed if outcomes are suboptimal, a long-term surgical strategy should preserve subsequent options and maximally prolong visual and ocular survival.

Pediatric glaucoma surgery can be divided into several broad categories: angle surgery (goniotomy or trabeculotomy), filtering surgery (trabeculectomy ± antifibrotic agents), aqueous drainage device (seton) surgery, cycloablation (cryotherapy or using laser), and others (such as peripheral iridectomy, combined trabeculotomy–trabeculectomy). Enucleation with prosthesis fitting may be the appropriate treatment for blind, disfigured, and painful eyes.

24.8.2.1Goniotomy

Goniotomy, the surgical procedure of choice in many cases of PCG, involves incising the uveal trabecular meshwork under direct visualization. Trabeculotomy ab externo (see Sect. 24.8.2.2), an alternative and equally effective procedure, can be performed even

when corneal opacity prevents adequate gonioscopic viewing of the angle structures (a prerequisite for goniotomy). The finding that approximately 70% of children with PCG can be cured by goniotomy (made by Barkan in 1942) dramatically improved the prognosis for this disease [9]. Goniotomy has also been reported as a prophylactic procedure in selected cases of congenital aniridia with progressive angle closure

[23].

Goniotomy – an elegant, brief procedure which nonetheless requires great surgical precision – requires a gonioscopic view of the angle, but spares conjunctiva for later surgery, and does not alter the globe’s resistance to infection or blunt trauma. Basic steps to goniotomy include: fixation of the globe, magnification and light source (loupes or microscope), operating goniotomy lens, and a sharp instrument for incision (goniotomy knife or disposable needle). Clearing of the mildly edematous cornea can be promoted by administering aqueous suppressant treatment (topical or oral carbonic anhydrase inhibitors, and timolol 0.25% in healthy infants/children) for a few days, and by application of Iopidine 0.5% as well as 5% sodium chloride drops on entering the operating room. Scraping the edematous corneal epithelium has not proved useful to the authors, who prefer trabeculotomy if the gonioscopic angle view is poor just prior to surgery. Iopidine 0.5% drops also minimize intraand immediate postgoniotomy bleeding, and pilocarpine 2% drops induce miosis to protect the crystalline lens during the procedure, and to place the iris on stretch during and for several weeks postgoniotomy.

Theauthors’preferredtechniqueutilizesamodified

Barkan goniotomy lens (with a handle), placed onto the cornea on a cushion of Healon. While the surgeon sits opposite the angle to be operated on (e.g., on the temporal side for nasal goniotomy), with the microscope tilted about 45 degrees, the assistant stabilizes the eye with locking forceps placed on the Tenon’s insertion near the limbus at 6 and 12 o’clock for a nasal or temporal goniotomy. Instead of a tapered knife, a disposable, 25-gauge needle on a syringe filled with

Miochol or viscoelastic is used to enter the peripheral cornea on the side opposite to the intended angle incision. After the needle has been guided over the iris to engage the anterior portion of the trabecular meshwork, rotation first in one direction, and then in

Fig. 24.13  Gonioscopic view of an eye with congenital glaucoma after successful goniotomy surgery, demonstrating a goniotomy cleft. The whitish cleft appears in the central portion of the view, where the angle is notably widened, revealing the ciliary body band

the opposite direction, produces the desired incision, which can be maximally extended to 4- to 5-clock hours, via slight globe rotation by the assistant. The resultant cleft appears in the wake of the incision, and

often the peripheral iris moves posteriorly as the angle widens; blood may appear in the angle, especially if the chamber shallows after the needle is carefully withdrawn from the eye (Fig. 24.13). If used at all, a small amount of viscoelastic may be injected just as the needle is withdrawn from the eye, the chamber is refilled with balanced salt, and the entry site closed with a single 10-0 Vicryl suture. A bubble of filtered air may be placed, and helps confirm a formed chamber easily in an infant on the first postoperative day. Subconjunctival antibiotic and short-acting steroid may be injected, and the eye shielded. Postoperatively, antibiotic, steroid, and miotics (except in uveitic glaucoma) are used for various time periods by different surgeons.

Goniotomy surgery has the highest reported success rate, from 70% to more than 90%, in infants with PCG diagnosed between 3 and 12 months of age. When PCG is of birth-onset, angle surgery often fails, probably due to a more severe angle defect;

PCG recognized later in childhood responds less well