Introduction

After Otto Barkan described the use of goniotomy as a primary treatment for congenital glaucoma in 1942, the prognosis for infantile glaucoma was markedly improved1,2. Barkan’s method of using a goniolens for incisional angle surgery under direct visualization continues to be useful with little modification. Trabeculotomy is an alternative approach that was independently described by Burian and Smith in 19603–4. This procedure involves canulation of Schlemm’s canal through a scleral incision with a trabeculotome, which is then rotated to rupture the trabecular meshwork. More recently, some glaucoma surgeons have utilized combined trabeculotomy and trabeculectomy as a primary procedure in patients judged to have a poor prognosis for success with initial goniotomy or trabeculotomy. This approach has been used most commonly in infants in the Middle East and India as well as in patients over 2 to 3 years of age.

Epidemiologic considerations and terminology

Developmental glaucoma refers to glaucoma associated with developmental anomalies of the eye present at birth. This broad term encompasses the majority of glaucomas occurring in infants and children. Primary developmental glaucoma describes glaucoma that results from maldevelopment of the aqueous outflow system. Secondary developmental glaucoma indicates that damage to the aqueous outflow system is due to maldevelopment of some other portion of the eye.

Primary congenital glaucoma is the most common form of glaucoma in children, occurring in approximately 1 in 10 000 births in western developed countries5. This condition results from an isolated maldevelopment of the trabecular meshwork (trabeculodysgenesis) and is not associated with other developmental ocular anomalies or ocular disease. Typically, it manifests at birth or early childhood, before age 3 years. The majority of patients are diagnosed by age 6 months, and 80% are diagnosed within the first year of life.

Secondary congenital glaucoma is characterized by increased intraocular pressure (IOP) in patients with developmental defects of the anterior chamber angle associated with ocular and sometimes systemic abnormalities. The genetic basis for these disorders may be known, and the condition is usually bilateral. Examples of anomalies often associated with glaucoma include Axenfeld–Rieger syndrome, Peters’ anomaly, aniridia, and the phacomatoses (e.g., Sturge–Weber syndrome). Metabolic diseases, persistent fetal vasculature, retinopathy of prematurity, and chromosomal anomalies are also often associated with secondary developmental glaucoma. Finally, aphakia/pseudophakia and uveitis are important causes of glaucoma in infants and young children.

Clinical features, diagnosis, and differential diagnosis

Primary congenital glaucoma presents classically with a triad of symptoms: epiphora, photophobia, and blepharospasm6. These symptoms arise due to corneal irritation accompanying corneal epithelial edema, which is secondary to increased intraocular pressure. Patients may also present with a ‘red eye’ that mimics conjunctivitis7.

Several clinical signs may be evident in primary congenital glaucoma. Ocular enlargement (buphthalmos) may occur under the influence of increased intraocular pressure, with the major enlargement occurring at the corneo-scleral junction6–8. The cornea may appear hazy or opacified, and breaks in Descemet’s membrane (Haab’s striae) may be present. Finally, optic nerve cupping can occur rapidly and early in infants with primary congenital glaucoma. Cupping of the optic nerve head may be reversible with normalization of the intraocular pressure in infants9. This finding is uncommon in an adult with glaucomatous optic nerve head damage.

Many of the clinical features of primary congenital glaucoma can be found in other conditions and must be considered in the differential diagnosis2. Other conditions may cause red eye, corneal enlargement, corneal edema, and optic nerve abnormalities. However, these clinical entities cannot be completely characterized by photophobia, tearing, blepharospasm, increased intraocular pressure, and generalized ocular enlargement with optic nerve cupping. Recognition of the type of glaucoma present in a pediatric patient often requires experience and knowledge.

Anatomic considerations

The anterior chamber angle exhibits characteristic ultrastructural changes in eyes with primary congenital glaucoma. Anterior iris insertion is accompanied by compact trabecular beams containing excessive extracellular matrix material. Proliferation of fibrous tissue at the inner wall of Schlemm’s canal has also been described10,11. These findings are consistent with non-differentiation of the trabecular meshwork and persistence of embryonic characteristics. Secondary forms of congenital glaucoma may demonstrate additional anomalies of the iris, cornea, and lens. Pigmentation of the trabecular meshwork is acquired with age; therefore, recognition of the lightly or non-pigmented trabecular meshwork in an infant may be difficult. Severe ocular enlargement, sclerocornea, and other abnormalities may render external landmarks for internal structures unreliable. In these instances, imaging techniques such as ultrasound and optical coherence tomography (OCT) or endoscopic techniques may be helpful.

Fundamental principles

Surgical intervention provides the most effective and definitive treatment for most developmental glaucomas. Medical therapy may serve a supportive role in temporarily reducing intraocular pressure and clearing the cornea until surgery can be performed. A minority of patients with congenital glaucoma may respond to medical therapy alone12. Some secondary glaucomas may respond to medical therapy, such as glaucoma associated with aphakia or pseudophakia. Commonly used glaucoma medications in pediatric patients include topical beta-blockers, carbonic anhydrase inhibitors, and prostaglandin analogs. Oral acetazolamide elixir (5–15 mg/kg/day) may also be administered. Alpha-2-agonists are avoided in young children due to problems with sedation and other untoward side effects.

Goals of surgery

The primary goal of therapy in the developmental glaucomas is to normalize and permanently control intraocular pressure, thereby preventing optic nerve damage and maintaining visual function. Early control of IOP is the key to limiting damage to ganglion cells and the optic nerve while preserving visual development (acuity and stereovision) and visual field.

The choice of surgical therapy for developmental glaucoma depends on multiple factors. Age is an important factor, because the best outcomes for goniotomy and trabeculotomy occur in children less than 2 or 3 years old. The structural defects associated with the increased intraocular pressure, patient age, corneal clarity and associated systemic syndromes guide one’s surgical approach. Primary surgical procedures for developmental glaucomas aim to overcome the resultant increased resistance to aqueous outflow by establishing, at least in part, communication between the anterior chamber and Schlemm’s canal.

Indications for surgery

The primary developmental glaucomas are highly responsive to both goniotomy and trabeculotomy. Goniotomy is the classic procedure for primary congenital glaucoma and can be useful in cases of uveitic glaucoma as well as to prevent glaucoma development in patients with aniridia13–15. It requires a clear or nearly clear cornea and gonioscopy surgical skills. Trabeculotomy is an alternative to goniotomy which is particularly useful in eyes with cloudy corneas that preclude a gonioscopic view of the angle. In recent years, combined trabeculotomy and trabeculectomy has been advocated as an alternative approach in refractory cases. When extensive iris structural defects accompany the trabeculodysgenesis, careful examination of the angle is important. In aniridia, for example, peripheral anterior synechiae formation and anterior stromal insertion add complexity to surgical decisions.

Preoperative assessment

For most pediatric patients under the age of 5, an exam under anesthesia (EUA) is the most accurate way to diagnose and monitor glaucoma. In most patients, a thorough examination under anesthesia is performed prior to surgical treatment. Key elements of the exam are:

After completion of the EUA, findings of corneal enlargement, optic nerve head cupping and buphthalmos often confirm the diagnosis of glaucoma and the need for surgical intervention. Also, findings from the EUA allow comparisons to aid in follow-up examinations of the patient.

Anesthesia

Anesthesia should be administered in the operating room by skilled individuals who have experience with pediatric patients. For brief examinations, intravenous and mask anesthesia often suffice. For more prolonged examinations or in cases where surgical treatment is likely at the time of examination, endotracheal intubation is preferred.

All anesthetics have the potential to alter intraocular pressure. Halogenated ethers such as halothane, sevoflurane, and desflurane cause rapid lowering of IOP16,17. Ketamine is known to cause a modest elevation in IOP18,19. Induction with ketamine may allow more accurate and consistent IOP measurements, particularly during the first 10 minutes following onset of anesthesia20. Standardization of anesthesia for intraocular pressure measurements for diagnosis and follow-up of primary developmental glaucoma is highly desirable. Inconsistent readings should always be interpreted with consideration of the patient’s general state of anesthesia and the specific anesthetic used.

Although rarely used in pediatric patients, systemic absorption of anti-cholinesterase drugs can significantly reduce the serum cholinesterase and pseudocholinesterase levels. Cholinesterase metabolizes succinylcholine and related drugs, which may have prolonged activity and cause apnea in patients treated with anti-cholinesterase drugs.

In about two-thirds of patients, congenital glaucoma is bilateral, which sometimes raises the question of simultaneous bilateral surgery2. Although potentially devastating, the risks are low for bilateral sight-threatening complications such as endophthalmitis. The risk of general anesthesia in infants, however, is also a concern, and can be reduced by performing simultaneous bilateral surgery. The surgeon should be aware of the risk of anesthesia for infants at their institution, which varies in different regions. The decision for simultaneous bilateral surgery should only be made with full participation of the patient’s family in the decision-making process.

Operation techniques

Goniotomy

Following induction of general anesthesia, a goniotomy lens such as the Swan-Jacob lens (alternatives include the Barkan lens or a wide angle goniotomy lens) is placed on the cornea. An operating microscope is preferred, though surgical loups with a headlight can be used. Modern operating microscopes can be tilted more than 45°, which allows for an excellent view of the anterior chamber angle through the gonio lens. Improvements in optics for the operating room are probably the most important current modification of goniotomy. For nasal goniotomy, the surgeon sits temporally and the lens is placed on the cornea with approximately 2 mm of temporal cornea exposed. Locking forceps can be placed by an assistant on the vertical recti muscles for a goniotomy performed nasally or temporally. An optional paracentesis may be performed at this stage. Most surgeons inject viscoelastic into the anterior chamber to prevent shallowing of the anterior chamber during the procedure.

The goniotomy knife enters the anterior chamber through peripheral clear cornea, approximately 1 mm inside the corneo-limbal junction opposite the planned incision site. The blade is guided across the anterior chamber toward the opposing trabecular meshwork. Care is taken to remain parallel to the iris and away from the pupil and lens. The tip of the knife is engaged slightly anterior to the middle of the trabecular meshwork (Fig. 42.1). Under the operating microscope, the tip of the knife can be seen to indent the trabecular meshwork before it is incised by circumferential movement of the knife.

Fig. 42.1 Goniotomy. The goniotomy knife is advanced across the anterior chamber with the aid of a gonioscope, with the tip of the knife engaging tissue just anterior to the middle of the trabecular meshwork.

The tip of the goniotomy knife should remain in a superficial position, cutting at a uniform depth along the incision. There should be little or no perceptible tactile sensation of cutting trabecular tissue. If a coarse, grating sensation is felt, the knife is likely positioned too deep. As the incision proceeds, a white line develops behind the blade, the peripheral iris falls posteriorly, and the angle deepens (Fig. 42.2). Great care should be taken to avoid touching the iris on the knife edge or damaging the lens. The incision may encompass 90–120^o circumferentially. However, with rotation of the globe by the assistant surgeon, up to 4 to 6 clock hours of meshwork can be incised in total (Fig. 42.3).

Fig. 42.2 Goniotomy. As the incision proceeds circumferentially, a white line indicates the position of the incision. Deepening of the anterior chamber angle may be noted behind the blade.

Fig. 42.3 Goniotomy (schematic). The trabecular meshwork is circumferentially incised, first in one direction and then the opposite direction.

Reprinted with permission from Mandal AK, Netland PA. The Pediatric Glaucomas. New York, NY: Elsevier, 2006.

Once the incision has been completed, the blade is carefully withdrawn avoiding the corneal endothelium, iris, and lens and maintaining the anterior chamber. A single 10-0 nylon or Biosorb suture can be used to close the incision site if the wound leaks. A moderate amount of bleeding is typical and indicates that communication between the anterior chamber and Schlemm’s canal has been achieved. This bleeding is innocuous and usually rapidly clears following surgery21,22. The entire procedure normally requires approximately 10 minutes to complete. A modification to the above approach is the use of coaxial endoscopy, which allows for goniotomy in patients with cloudy corneas23–25.

Trabeculotomy

An initial fornix- or limbus-based conjunctival flap is followed by a paracentesis to facilitate maintaining the anterior chamber. Next, a limbus-based partial thickness scleral flap is made to a depth of approximately one-half scleral thickness, bearing in mind that the sclera in buphthalmic eyes is usually much thinner than in the adult eye (Fig. 42.4A).

Fig. 42.4 Trabeculotomy. After formation of the conjunctival flap, a scleral flap is fashioned to approximately one-half scleral thickness in a shape according to surgeon preference (A). A radial incision bridging the scleral spur is carefully made with the goal of cutting the external wall of Schlemm’s canal (B). After probing Schlemm’s canal, the metal trabeculotome is carefully inserted into the canal with the external arm serving as a guide (C).

Photographs provided by Ronald L. Fellman, MD.

The junction of the posterior border of the trabecular band and the sclera is the landmark for the scleral spur and for finding Schlemm’s canal. In most eyes this is situated between 2 and 2.5 mm behind the surgical limbus. A radial incision is then made across the scleral spur with the goal of cutting the external wall of Schlemm’s canal without entering the anterior chamber (Fig. 42.4B). Because Schlemm’s canal is separated from the anterior chamber only by the trabecular meshwork, this is the most delicate step in the operation and demands the most microsurgical skill.

Under high magnification, the radial incision is gradually deepened with a sharp blade until it is carried through the external wall of Schlemm’s canal, at which point there is ooze of aqueous, occasionally mixed with blood. The inner wall is identified by its mild pigmentation and composition of crisscrossing fibers. Confirmation of Schlemm’s canal may be made by passing a blunt canula or 6-0 nylon suture into the canal without resistance26.

The internal arm of the trabeculotome is introduced into the canal using the external arm as a guide (Fig. 42.4C). Once 90% of the trabeculotome resides in the canal, it is rotated into the anterior chamber until 75% of the probe arm length has entered the chamber (Fig. 42.5). Care must be taken to avoid trauma to the iris and peripheral cornea. The rotation is reversed and the instrument is withdrawn. Approximately 2– clock hours of the internal wall of Schlemm’s canal and trabecular meshwork are disrupted by this maneuver. The trabeculotome is then passed into Schlemm’s canal on the other side of the radial incision and the procedure is repeated. In total, 100–120° of trabecular meshwork are ruptured.

Fig. 42.5 Trabeculotomy with a metal trabeculotome (schematic). (A) Rigid metal trabeculotome positioned in Schlemm’s canal. (B) Rotation of the trabeculotome into the anterior chamber with rupture through the inner wall of Schlemm’s canal and trabecular meshwork.

If the probe does not slip easily down the canal, it should be withdrawn and dissection of the outer wall continued until the surgeon is satisfied that all fibers of the outer wall are removed. Forceful introduction of the probe in the region of Schlemm’s canal can create a false passage. During rotation of the trabeculotome into the anterior chamber, some light resistance is expected, and intracameral bleeding from the inner wall may occur27–29. As with goniotomy, this bleeding is usually transient, resolving within a few days after surgery.

As the probe is swung from the canal into the anterior chamber, movement of the iris may indicate that the probe is too posterior. The probe should be repositioned to avoid iridodialysis. Also, the surgeon must be careful not to pass the probe anteriorly into the cornea. This is easy to detect because there is resistance to rotation of the instrument, and small air bubbles may appear in the cornea as the probe ruptures corneal lamellae. In highly buphthalmic eyes, Schlemm’s canal may not be located with certainty. In such cases it is possible to convert the procedure to a trabeculectomy by removing a block of deep limbal tissue beneath the scleral flap.

Numerous modifications to trabeculotomy have been described. Redmond Smith developed a modification that he called ‘nylon filament trabeculotomy’, which involved cannulating Schlemm’s canal and threading the suture circumferentially, withdrawing it at another site, and pulling it tight like a bowstring30. Beck and Lynch described a 360° trabeculotomy using a blunted 6-0 polypropylene suture31. The suture was threaded through Schlemm’s canal and retrieved either through the original radial incision or through a second radial incision 180° away (Fig. 42.6). This technique can be performed via a single nasal surgical site with the two ends of the passed suture tightened until the suture is pulled into the anterior chamber. More recently, ophthalmic microcatheters have been used in suture trabeculotomy to provide visual cues during cannulation and allow viscodilation of Schlemm’s canal32.

Fig. 42.6 Two-site 360-degree suture (filamentary) trabeculotomy. In cases where a surgeon is unable to pass the suture completely around to the original incision, a second site is required to find the suture. After completing the pass, the opposite ends of the suture are grasped and the suture is bow stringed into the anterior chamber.

Combined trabeculotomy–trabeculectomy

The operative procedure and postoperative appearance are shown in Fig. 42.7. Following an initial trabeculotomy as described above, a trabeculectomy may be performed by making an incision at the surgical limbus with a sharp blade under the original scleral flap. A Descemet’s punch is used to create a sclerostomy. Alternatively, a block of sclera may be removed using a sharp blade and Vannas scissors. After performing a surgical iridectomy, the partial thickness flap is closed with interrupted 10-0 nylon sutures. Alternatively, one may use absorbable suture material such as 9-0 Vicryl (polyglactin) to encourage aqueous flow during the postoperative period. Conjunctiva and Tenon’s capsule are closed in a running fashion with absorbable 9-0 polyglactin sutures on a BV needle.

Fig. 42.7 Combined trabeculotomy and trabeculectomy (limbus-based approach). Upon completion of the trabeculotomy (A), a sclerostomy is prepared (B). A Descemet’s punch may be used to prepare the sclerostomy. A peripheral iridectomy is performed, and the scleral flap is closed with interrupted sutures (C). The postoperative appearance, with formation of a bleb (D).

Reprinted with permission from Mandal AK, Netland PA. The Pediatric Glaucomas. New York, NY: Elsevier, 2006.

If mitomycin C is used during the procedure, it should be applied after the initial partial-thickness scleral flap for trabeculotomy. Successful outcomes have been reported after trabeculotomy-trabeculectomy with and without mitomycin C2. When used intraoperatively, the usual concentration of mitomycin C ranges from 0.2 to 0.5 mg/cc applied for 1–3 minutes.

Intraoperative complications

The efficacy and safety profile of goniotomy surgery are dependent on surgical experience and technique. Serious complications are rare. A transient hyphema occurs in the majority of cases but usually resolves within 1 week. Potential complications that have been reported include iridodialysis, cyclodialysis, shallowing of the anterior chamber, retinal detachment, iris incarceration, and epithelial ingrowth33,34. Damage to the lens and progression of cataract formation can also occur.

The risks of trabeculotomy are often related to performing angle surgery without direct visualization. Identifying key surgical landmarks can be challenging in eyes with marked buphthalmos or significant corneal edema. Potential complications include cyclodialysis, iris trauma, Descemet’s detachment, prolonged hyphema, intraocular pressure spike, shallowing of the anterior chamber, postoperative hypotony, retinal detachment and progression of cataract formation. False passages and inadvertent bleb formation have also been reported29,35. Combined trabeculotomy–trabeculectomy has a risk profile similar to trabeculotomy with perhaps an increased risk of vitreous prolapse during sclerostomy formation and surgical iridectomy36.

Postoperative care

After surgery, an antibiotic–corticosteroid preparation is injected under the conjunctiva and instilled into the inferior conjunctival fornix, and a patch and shield are applied to the eye. The patch can be removed on the first postoperative day. After uncomplicated goniotomy, the shield only (without the patch) may be used. Topical antibiotic–steroid drops are continued until the anterior chamber reaction resolves, usually a period of 4–6 weeks. Any remaining non-absorbable sutures can be removed after 4–6 weeks following surgery.

Between 3 and 6 weeks after surgery, the postoperative control of the intraocular pressure can be assessed. The degree of relief from photophobia, tearing, and blepharospasm usually reflects the effectiveness of surgery and may reasonably predict whether or not additional surgery is required. Infants and children with developmental glaucoma must be followed periodically to determine if adequate control of intraocular pressure has been achieved. Much of the follow-up can be performed in the office setting, though young children may need occasional examinations under anesthesia.

Assessment of surgery

Goniotomy for developmental glaucoma has a high success rate of approximately 80%, ranging from 70% to 93% in most large series21,33,37.

It appears that goniotomy is most successful in patients whose glaucoma is recognized early and treated between 1 month and 1 year of age, though good success rates are achieved in patients up to 2 years of age33. Russell-Eggitt et al.37 reported a relapse rate of approximately 2–3% per year over 30 years in eyes that had initially been controlled for IOP after one or more goniotomies. Thus, regular surveillance of these patients is needed.

Trabeculotomy in patients with primary developmental glaucoma shows similar results compared with goniotomy. McPherson and Berry reported that 22 (96%) of 23 eyes following trabeculotomy had an intraocular pressure under 21 mmHg at a mean follow-up of 5.6 years27. Ikeda et al.38 studied the long-term outcome of 149 patients with primary or secondary developmental glaucoma who underwent one or more trabeculotomy surgeries. Patients with primary developmental glaucoma had a 47% mean reduction in IOP following a single trabeculotomy with an average follow-up of 9.5 years. Likewise, patients with secondary developmental glaucoma had a 38% mean reduction in IOP following a single trabeculectomy with an average follow-up of 8.1 years. A trend of effective intraocular pressure control was maintained over 18 years in both groups. Success probabilities at 20 years were 80.8% for eyes with primary developmental glaucoma and 64.2% for eyes with secondary developmental glaucoma.

Long-term results of combined trabeculotomy and trabeculectomy have been described by Mandal et al.36 who reported long-term outcomes of 299 eyes of 157 consecutive Indian patients with primary congenital glaucoma. Success probabilities were 94.4% at 1 year and 63% at 8 years (Fig. 42.8). Mullaney et al.39 reviewed 100 consecutive eyes in 60 patients with infantile glaucoma treated with combined surgery (most received mitomycin C, 0.2 or 0.4 mg/cc). Successful control of IOP was achieved in 78% of eyes with primary developmental glaucoma, but in just 45% of eyes with anterior segment anomalies, with an average follow up of approximately 10 months. Combined trabeculotomy–trabeculectomy is a safe and effective alternative procedure for patients with developmental glaucoma who present with hazy media and respond poorly to primary trabeculotomy alone, as in India and parts of the Middle East. Moreover, the combined surgery establishes two major outflow pathways for IOP control, a theoretical advantage in poor prognosis patients.

Fig. 42.8 Long-term success after combined trabeculotomy and trabeculectomy. Children with developmental glaucoma underwent treatment within 6 months of birth, with 142 eyes included in analysis. Success was defined as intraocular pressure <21 mmHg with no progression of disc cupping or corneal diameter. The Kaplan–Meier curve shows the complete success probabilities.

Modified with permission from Mandal AD, Bhatia PG, Bhaskar A, Nutheti R. Long-term surgical and visual outcomes in Indian children with developmental glaucoma operated on within 6 months of birth. Ophthalmology 2004;111:283–90.