CLASSIFICATION OF GLAUCOMAS

The classification of glaucomas has seen a progressive change as our understanding of this condition has evolved. The anatomic, gonioscopic, biochemical, molecular and genetic basis for the classification of glaucomas has been utilized, each having its own pros and cons. With the advent of new instruments to diagnose glaucoma, classifications have also been created based on the techniques utilized. Thus, the classifications of glaucoma include those based on:

-Etiology

-Mechanism

-Staging

-Optic nerve appearance

-Visual field damage

-Standard HRT parameters by bagging classification trees

-Automated classification of glaucoma stages using higher order cumulant features

-Texture features using neural networks

Unfortunately, none of the classifications have been satisfactory in their attributes to describe glaucoma. This is not unexpected, since there are different mechanisms of the disease and multifactorial pathogenetic factors at work in different individuals. Presently, the classification of glaucomas based on etiology and mechanism is still applied in clinical practice, having stood the test of time over the years.

Etiologic Classification= This is based on the underlying disorder causing alteration in aqueous inflow/outflow (Aqueous humor dynamics) or Retinal Ganglion Cell (RGC)/Optic nerve damage. 

Mechanistic Classification= This is based on specific alteration in the anterior chamber (AC) angle that causes intra-ocular pressure (IOP) to rise.

These classifications have incorrectly been based on our focus on elevated IOP as the major risk factor for the development of glaucoma, excluding other factors such as vascular, genetic or biochemical mechanisms among others.

CLASSIFICATION BASED ON ETIOLOGY 

Based on the etiology, glaucomas have been divided into primary and secondary. The primary glaucomas are assumed to have the initial events leading to outflow obstruction and IOP elevation primarily in the AC angle or conventional outflow pathway. These glaucomas are not associated with known ocular or systemic disorders which could impede aqueous outflow. They are usually bilateral and probably have a genetic basis. From a therapeutic standpoint it is essential to differentiate open angle glaucoma from closed-angle glaucoma.

On the other hand, secondary glaucomas are regarded as such because of a “partial understanding of the underlying, predisposing ocular or systemic events” [Bruce Shields]. These are usually asymmetric or unilateral. While some may have a genetic basis, others are acquired. As the concepts regarding the underlying causes of the glaucomas continue to develop, the primary and secondary classifications have become increasingly artificial and inadequate.

Classification of childhood glaucomas, especially those associated with developmental anomalies of the anterior chamber angle have been dogged by overlapping and variably defined nomenclatures which frequently denotes the age of onset rather than the underlying mechanism for the glaucoma. 

Bruce Shields has recommended replacing traditional concepts with a new scheme that provides a “better working foundation for the concepts of mechanism, diagnosis and therapy that will shape the management of glaucomas for the foreseeable future”. He has classified glaucomas based on staging. According to him, glaucomas can be considered to consist of 5 stages:

Stage I: Initiating events

Stage II: Structural alterations

Stage III: Functional alterations

Stage IV: RGC and ON damage

Stage V: Visual loss

The initiating events (Stage I) are speculated to have a genetic basis. Structural changes may start occurring in the RGCs or optic nerve head (ONH), as a result of alterations in proteins in these regions. These structural alterations (Stage II) could be subtle tissue changes in the blood vessels supplying the ONH or in supportive elements of the lamina cribrosa. Or they could act through mechanisms as yet to be understood. Structural changes may lead to functional alterations (Stage III) such as reduced axonal conduction, vascular perfusion to axons in the ONH or a progressive deformity of the lamina cribrosa that may lead (alone or in conjunction with a relative IOP elevation) to glaucomatous optic neuropathy (Stage IV), which gets reflected in subsequent VF changes (Stage V).

Traditionally, glaucomas have been divided into open and closed angle.

Chronic open angle glaucoma: This is characterized by optic nerve damage in an eye which does not have evidence of angle closure on gonioscopy and there is no identifiable secondary cause. Apparently inherited susceptibilities lead to increased resistance to aqueous outflow and higher vulnerability of the ONH to the level of IOP.

Pupillary block glaucoma: Primary Angle Closure includes asymptomatic individuals with occludable angles who have not had an acute attack, as well as those who had an attack which resolved spontaneously or with treatment prior to the development of any detectable nerve damage. Primary Angle Closure Disease (PACD) has been classified by the International Society for Geographical and Epidemiological Ophthalmology (ISGEO) into:

(1) Primary Angle Closure Suspect (PACS): Such eyes have iridotrabecular contact for atleast 270⁰ and normal IOP, ONH and VFs.

(2) Primary Angle Closure (PAC): There is iridotrabecular contact for atleast 270⁰ and raised IOP and/or peripheral anterior synechiae (PAS), but with normal ONH and VFs.

(3) Primary Angle Closure Glaucoma (PACG): There is PAC with evidence of glaucomatous damage in the ONH or VFs.

(4) Acute Angle Closure Crisis: There is periocular or ocular pain, often accompanied by headache, nausea or vomiting, IOP >21 mmHg, circumcorneal congestion, corneal edema, mid-dilated pupil and shallow anterior chamber.

Developmental anomalies of AC Angles:

These represent incomplete development of structures in the conventional aqueous outflow pathway. These anomalies could be inherited or acquired during intra-uterine life and lead to elevation of IOP. In some cases the developmental anomaly is not associated with primary or systemic etiologies and regarded as primary.

Pediatric glaucomas have been classified into the following categories:

(1) Primary Congenital Glaucoma (PCG): Primary congenital glaucoma that occurs at or shortly after birth or glaucoma of any etiology that occurs in the same time frame.

(2) Primary Infantile Glaucoma: It is genetically identical to PCG but presents 1-2 months after birth.

(3) Juvenile Open Angle Glaucoma: There is no ocular enlargement; absent congenital ocular anomalies or syndromes; Open, normal appearing angles; meets the glaucoma definition.

(4) Developmental Glaucoma: This term has been used as a giant waste basket for nearly all childhood glaucomas that are not acquired immediately after birth.

Glaucomas associated with other ocular disorders

This class includes those glaucomas in which the initiating event is an abnormality of the ocular structures such as corneal endothelium, iris, ciliary body, lens, vitreous, retina and so on. Or the initiating event is a definite second ocular pathology such as tumor, hemorrhage, inflammation and so on. Secondary glaucomas are properly considered to represent those eyes in which a second form of ocular pathology has caused IOP to rise above the normal range with consequent ON damage. The second ocular pathological processes causing optic neuropathy may include=

      i.        Neovascularization

     ii.        Uveitic conditions

    iii.        Trauma

   iv.        Lens-related

CLASSIFICATION BASED ON MECHANISM

Elevated IOP is the major risk factor for the development of glaucoma. However, the concept that statistically raised IOP is a defining characteristic of glaucoma has been almost universally discarded. A disadvantage of this mechanistic system is that it ignores the causes unrelated to IOP. Also, many of the glaucomas have more than one mechanism of outflow obstruction at different times in the course of disease. As a result some of the glaucomas must be classified under more than one mechanistic heading. On the plus side, the advantage of this classification is that our understanding of the mechanisms of aqueous outflow obstruction is usually more complete than our knowledge of initiating events. An understanding of the mechanism that leads to aqueous outflow obstruction is important in developing a rationale for controlling the IOP in each form of glaucoma.

Mechanisms of Open Angle Glaucoma=

The elements obstructing aqueous outflow may be located on the anterior chamber side of the trabecular meshwork [TM] (pretrabecular mechanisms); in the TM (trabecular mechanisms) or distal to the meshwork, in the Schlemm’s canal or further along the aqueous drainage system (post trabecular mechanisms).

Angle closure glaucoma mechanisms=

Angle closure mechanisms are the ones which cause apposition of the peripheral iris to the TM or peripheral cornea. The peripheral iris may be pulled (anterior mechanisms) or pushed (posterior mechanisms) into this position. In anterior mechanisms usually a contracting membrane in front of the iris pulls the iris towards the TM/peripheral cornea. It can also be caused by consolidation of inflammatory products in this area.

In posterior mechanisms pressure behind the iris, lens or vitreous causes the peripheral iris to be pushed into the anterior chamber angle. These mechanisms can occur with or without pupillary block. Pupillary block variants include pupillary block glaucoma in which there is apposition of the mid-periphery of the iris and the lens, thus blocking the egress of aqueous anteriorly through the pupil. The peripheral iris balloons in the form of “iris bombe”. The functional apposition in these patients is due to a genetically influenced configuration of the anterior segment of the eye. Such appositions may also be seen in lens-induced mechanisms such as phacomorphic glaucoma or ectopia lentis. Pupillary block can also occur from posterior synechiae. The “pushing” mechanisms can also occur without pupillary block such as ciliary block (malignant glaucoma), lens induced, forward shift of vitreous following lens removal, intraocular tumors, cysts of uveal tract, retrolenticular tissue contraction as in retinopathy of prematurity or persistent fetal vasculature.

Developmental anomalies of the AC Angles=

These represent incomplete development of structures in the conventional aqueous outflow pathway. Examples of these include: congenital glaucoma, Axenfeld-Reiger syndrome, Peter anomaly and iridocorneal adhesions.