Mordechai Goldenfeld,
Shlomo Melamed
INTRODUCTION
Juvenile-onset open-angle glaucoma (JOAG) is a rare form of open-angle glaucoma (OAG), which is often associated with myopia and demonstrates an autosomal dominant inheritance.
JOAG should be differentiated from other forms of childhood glaucomas like congenital glaucoma and other developmental and secondary childhood glaucomas.
The estimated occurrence is 1 per 50 000 persons, and it equally affects males and females, with no racial susceptibility.
DEFINITION
Although in the past there was some confusion regarding the exact defiition of JOAG. The European Glaucoma Society defied JOAG as OAG with onset between 10 and 35 years of age, associated in many cases with a positive family history, and with an association to a gene mutation on chromosome 1 (1q21-q23) and MYOC.
JOAG suspect was defied as an increase in intraocular pressure (IOP) >31 mmHg in the same age group with a positive gene mutation on chromosome 1 (1q21-q23) and MYOC or with at least two risk factors: (1) IOP >22 mmHg <30 mmHg; (2) IOP difference between eyes of more than 4 mmHg; (3) family history of glaucoma; and (4) manifest JOAG in the other eye.[1]
Descriptive terms such as primary OAG of adolescents and young adults, late congenital glaucoma,[2-4] or developmental glaucoma[3] have failed to distinguish this disorder from other glaucomas. Ellis suggested that JOAG results from a congenital remnant of the pectinate ligament.[5] Scheie defied JOAG as primary OAG found in older children and in young adults up to 30 years of age.[6,7] Gorin characterized gonioscopic features related to this disease such as abnormal width and prominence of the trabecular meshwork, absence of angle recess, and mesodermal remnants in the angle.[3] Melamed and associates described open angles with various gonioscopic fidings such as thickened, membrane-like trabecular meshwork, prominent iris processes that may cover the ciliary body band and scleral spur, and a high iris insertion.[8] These fidings suggest that maldevelopment of the angle structures is an important component of the pathology in this disorder.
GENETICS OF JOAG
Studies suggest an autosomal dominant pattern of inheritance.[9,10] Genetic mapping studies have led to the discovery of several genetic markers on chromosome 1q in genetic linkage with autosomal dominant JOAG.[11,12] Subtracted cDNAs from a human ciliary body library encoding TIGR, a candidate gene for JOAG, have been cloned and classified by Ortego and colleagues.[13]
In 1993 Sheffield et al[14] reported the association of a gene mutation in chromosome 1 (1q21-q23), (GLCIA) with JOAG, Their report was confirmed by other researches[15] that confirmed the association between this gene mutation and an autosomal dominant JOAG.[16-18] The gene mutation on chromosome 1 (1q21-q23), encodes the myocilin protein, (MYOC). Later reports by Alward et al revealed four specific mutations that were linked with a form of OAG at the age range that corresponds to JOAG (Table 199.1).[19] Depending on the site and nature of the mutation in MYOC/TIGR, most patients with GLC1A-linked JOAG have higher IOP and a more severe course of disease than with other forms of POAG. This observation suggests that MYOC/TIGR normally has an important function in aqueous humor outflow and that this function is impaired if abnormal gene products are formed. So far, the nature of this function is unknown.
TABLE 199.1 -- Clinical Correlation to Mutations Identified in JOAG
|
Mutations Identified in Probands |
||||
|
Gene |
GLY364Val |
396IN53q7 |
TYR437His |
ILE477ASN |
|
Age at diagnosis |
22-48 |
19-31 |
8-41 |
12-41 |
|
Mean age |
34 |
25 |
20 |
21 |
|
IOP range |
15-65 |
12-60 |
14-77 |
20-52 |
|
Mean IOP |
36 |
40 |
44 |
40 |
|
Number of families |
2 |
6 |
27 |
13 |
|
Positive affected/negative affected ratio |
16/1 |
6/1 |
27/10 |
3/0 |
Modified from Alward WL, Fingert JH, Coote MA, et al: Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene (GLC1A). N Engl J Med 1998; 338:1022-1027.
MYOC/TIGR in the aqueous humor takes part in the modulation of outflow facility and has the tendency to decrease rather than increase trabecular aqueous humor outflow whether the protein interacts with other proteins to form large aggregates or just simply clogs the pores remains to be determined. The mechanism by which the MYOC/TIGR obstructs the flow in the filters is not known.[15]
PATHOPHYSIOLOGY
The strong family history of glaucoma in many of these patients, along with the gonioscopic fidings of a thickened trabecular meshwork, high iris insertion, and prominent iris processes, is strongly suggestive of angle maldevelopment as the basic pathophysiologic mechanism in JOAG. Tawara and Inomata confirmed the possible role of an abnormal, compact trabecular meshwork in a histopathologic study of specimens from patients with JOAG.[20] The compact trabecular meshwork contained cells with fie processes and an abnormal accumulation of extracellular material in the trabecular spaces. These investigations suggested that this tissue might represent an immature development of the aqueous drainage system and account for the increased resistance to aqueous outflow. Decreased outflow facility values have been reported in patients with JOAG,[8] confirming the important role of trabecular pathology in this disease.
CLINICAL SIGNS AND SYMPTOMS
Usually, the diagnosis of JOAG is made in routine eye examination, relatively late in the process of the disease. Similar to primary OAG, there are no alarming signs such as pain, ocular irritation, or visual loss that might prompt early detection. Occasionally, however, some patients have ocular pain and discomfort associated with an elevation of IOP. Colored haloes have been described by some patients. IOP is usually elevated in both eyes. Interestingly, despite high levels of IOP, corneal edema, ciliary congestion, and uveitis are rarely seen. Typically, pressures as high as 50 mmHg may be measured, and the IOP pattern may be brittle, with marked elevations and reductions of IOP over time. The slit-lamp examination is usually unremarkable, gonioscopic fidings of wide open angles with a thickened trabecular meshwork, high insertion of the iris, and prominent iris processes are important in making the proper diagnosis (Table 199.2). However, normal-looking angles do not preclude the diagnosis of JOAG.
TABLE 199.2 -- Gonioscopic Features of JOAG
|
Open angle |
|
High insertion of the iris |
|
Prominent iris processes |
|
Thickening of the trabecular meshwork |
|
Grayish pale color of the trabecular meshwork |
The optic disks vary from being entirely normal to having advanced glaucomatous cupping. Similarly, the visual fields may be full or display typical glaucomatous changes.
DIFFERENTIAL DIAGNOSIS
All young patients diagnosed with glaucoma who are aged 5-35 years may have JOAG. One should make the diagnosis of JOAG only when all other subtypes of glaucoma associated with other anomalies or related fidings have been excluded. Except for the case of late congenital glaucoma that may be difficult to differentiate from JOAG if Haab's striae are not present, most of the other cases of developmental glaucomas are easily distinguishable from JOAG. The list of differential diagnoses is summarized in Table 199.3. Special care should be mentioned to posttraumatic glaucoma, since apart from a recessed angle, it may be indistinguishable from JOAG. Although posttraumatic glaucoma is typically unilateral, it is documented that the prevalence of POAG in the other, untraumatized, eye is high, therefore it may present as an elevated IOP bilaterally when found late in the course of the disease. Gonioscopy may reveal various degrees of angle recession or peripheral anterior synechiae.
TABLE 199.3 -- Differential Diagnosis of JOAG with Associated Ocular and Extraocular Anomalies
|
Associated Ocular Anomalies |
||||||
|
Viscocanalostomy |
Prominent Schwalbe's Ring |
Chamber Angle Anomalies |
Iris Abnormalities |
Lens Abnormalities |
Retinal Abnormalities |
Extraocular Abnormalities |
|
Late congenital glaucoma |
? |
+ |
? |
? |
? |
? |
|
Sturge-Weber |
? |
? |
? |
? |
? |
+ |
|
Aniridia |
+ |
+ |
? |
+ |
± |
|
|
Axenfeld's anomaly |
+ |
+ |
? |
? |
? |
? |
|
Rieger's anomaly |
+ |
+ |
+ |
? |
? |
? |
|
Rieger's syndrome |
+ |
+ |
+ |
? |
? |
+ |
|
Peter's anomaly |
+ |
+ |
+ |
? |
? |
|
|
Pigmentary glaucoma |
? |
? |
+ |
? |
+ |
? |
|
Posttraumatic glaucoma |
? |
? |
± |
± |
? |
? |
|
Earlyonset POAG |
? |
? |
? |
? |
? |
? |
TREATMENT OF JOAG
In this section, we discuss the various treatments of JOAG (see Table 199.4).
TABLE 199.4 -- Treatment Options for JOAG
|
Medical treatment |
|
Laser therapy |
|
Argon laser trabeculoplasty |
|
Nd:YAG laser trabeculotomy |
|
DCPC |
|
Surgical treatment |
|
Trabeculotomy |
|
Filtering surgery |
|
Viscocanalostomy |
|
Setons |
MEDICAL THERAPY
Medical therapy is often insufficient to control IOP in patients with JOAG.[21] In addition to poor responsiveness to medical therapy, patients with JOAG are often noncompliant because of side effects of medications and the general youth of this patient population.
Even the introduction of new antiglaucoma medications as prostaglandin analogs, brimonidine and topical carbonic anhydrase inhibitors did not alter the relative inefficacy of medical therapy in JOAG.[22]
LASER THERAPY
Argon Laser Trabeculoplasty
Argon laser trabeculoplasty is generally believed to have little value in this disease.[23] Apparently, the thick and compact trabecular tissue is less affected by the laser energy. This treatment modality may be tried before traditional surgical interventions in patients in whom the trabecular meshwork seems normal and the trabecular band is more pigmented or in the older patient.
Neodymium:Yttrium-Aluminum Garnet Laser Trabeculotomy
The role of the maldeveloped, compact trabecular meshwork in the pathophysiology of JOAG has been confirmed by a histopathologic study.[20] Cutting through such an abnormal trabecular tissue has become an attractive concept in treating these patients either surgically, by goniotomy or trabeculotomy,[2,3,6,7,23,24] or with the neodymium:yttrium-aluminum garnet (Nd:YAG) laser.[8,25,26]
Melamed and associates reported that in 75% of eyes treated with Nd:YAG laser trabeculotomy (Nd:YAGLT) the procedure was initially successful in controlling IOP. Success of the treatment appeared to be related to perforation of Schlemm's canal creating a communication with the collector channel system. The occurrence of blood reflux into the anterior chamber was seen in all successfully treated eyes. In many of the eyes treated, outflow facility was found to be substantially increased after the procedure. However, in spite of the initial success, long-term follow-up failed to demonstrate a sustained reduction in IOP.[27]
Diode Laser Cyclophotocoagulation
Diode laser cyclophotocoagulation (DCPC) is usually indicated in refractory cases of JOAG, when conventional surgery has failed. It is safe and effective, although in JOAG multiple applications may be needed in the long term.[28]
SURGICAL TREATMENT
TRABECULOTOMY
Surgical trabeculotomy, whether performed internally from the anterior chamber[2,6,7] or externally from the sclera, has shown relatively good results. Trabeculotomy has a documented higher success rate than goniotomy. The latter controls IOP in ?74-85% of eyes with congenital glaucoma.[28] Trabeculotomy, in patients with JOAG, lowers IOP in 84%, and after a second operation, the success rate is 89%.
FILTRATION SURGERY - TRABECULECTOMY
Trabeculectomy was less successful in the JOAG group[29] when compared to POAG, mainly due to the excessive wound-healing response in younger patients, resulting in subconjunctival fibrosis. The results published reported in 1986 by Beauchamp and Parks[30] of a 50% success rate in cases of congenital glaucoma and in patients with JOAG have changed drastically with the introduction of mitomycin C (MMC) to glaucoma filtration surgery and to the treatment of JOAG. Reports of a 90-91% success rate of trabeculectomy with intraoperative use of MMC in JOAG were published. In a report by Jacobi and colleagues, the success rate was 91% at 1 year and 73% at 5 years for the control group that underwent trabeculectomy alone, versus 91% at 1 year and 5 years, for the MMC group. At fial visit, mean IOP was significantly lower for the MMC group (13.3 ± 3.9 mmHg) than for controls (18.0 ± 1.3 mmHg).[31]
VISCOCANALOSTOMY
Primary viscocanalostomy has recently been reported as a possible initial surgery in JOAG. Stangos and associates report an 80% success rate; however, the mean preoperative IOP (±SD) was 22.9 ± 4.77 mmHg, a relatively low IOP when considering JOAG.[32]
IMPLANTATION OF SETONS
In an attempt to overcome the problem of scarring conjunctiva, Molteno and associates suggested the use of an aqueous drainage device for IOP control in refractory cases of what they described as JOAG.[33] The concept of bypassing the scarred anterior conjunctiva by inserting the silicone tube into the anterior chamber and placing the collecting plate at the equator has proved superior to repeated standard filtration surgery in these patients. However, even with the Molteno implant, a thick fibrous tissue or a Tenon cyst may form around the plate and result in IOP elevation, requiring additional surgery. In addition, one should bear in mind that the population of patients reported by Molteno or other researchers with different setons (e.g., Baervaldt, Ahmed valve) have an array of diagnoses, and only a minority of the reported cases had JOAG with no associated ocular anomalies We recommend the use of setons in JOAG in refractory cases where trabeculectomy with intraoperative MMC had failed.
|
Key Features: Juvenile-Onset Open-Angle Glaucoma |
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General
Genetics
Differential diagnosis
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REFERENCES
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