PRIMARY OPEN ANGLE GLAUCOMA AND RELATED CONDITIONS PRIMARY OPEN ANGLE GLAUCOMA As the name implies, it is a type of primary glaucoma, where there is no obvious systemic or ocular cause of rise in the intraocular pressure. It occurs in eyes with open angle of the anterior chamber. Primary open angle glaucoma (POAG) also known as chronic simple glaucoma of adult onset and is typically characterised by slowly progressive raised intraocular pressure (>21 mmHg recorded on at least a few occasions) associated with characteristic optic disc cupping and specific visual field defects. ETIOPATHOGENESIS Etiopathogenesis of POAG is not known exactly. Some of the known facts are as follows: (A) Predisposing and risk factors. These include the following: 1. Heredity. POAG has a polygenic inheritance. The approximate risk of getting disease is 10% in the siblings, and 4% in the offspring of patients with POAG. 2. Age. The risk increases with increasing age. The POAG is more commonly seen in elderly between 5th and 7th decades. 3. Race. POAG is significantly more common, develops earlier and is more severe in black people than in white. 4. Myopes are more predisposed than the normals. 5. Diabetics have a higher prevalence of POAG than non-diabetics. 6. Cigarette smoking is also thought to increase its risk. 7. High blood pressure is not the cause of rise in IOP, however the prevalence of POAG is more in hypertensives than the normotensives. 8. Thyrotoxicosis is also not the cause of rise in IOP, but the prevalence of POAG is more in patients suffering from Graves’ ophthalmic disease than the normals. (B) Pathogenesis of rise in IOP. It is certain that rise in IOP occurs due to decrease in the aqueous outflow facility due to increased resistance to aqueous Fig. 9.7. Technique of trabeculotomy. GLAUCOMA 215 outflow caused by age-related thickening and sclerosis of the trabeculae and an absence of giant vacuoles in the cells lining the canal of Schlemm. However, the cause of these changes is uncertain. (C) Corticosteroid responsiveness. Patients with POAG and their offspring and sibilings are more likely to respond to six weeks topical steroid therapy with a significant rise of IOP. INCIDENCE OF POAG It varies in different populations. In general, it affects about 1 in 100 of the general population (of either sex) above the age of 40 years. It forms about onethird cases of all glaucomas. CLINICAL FEATURES Symptoms 1. The disease is insidious and usually asymptomatic, until it has caused a significant loss of visual field. Therefore, periodic eye examination is required after middle age. 2. Patients may experience mild headache and eyeache. 3. Occasionally, an observant patient may notice a defect in the visual field. 4. Reading and close work often present increasing difficulties owing to accommodative failure due to constant pressure on the ciliary muscle and its nerve supply. Therefore, patients usually complain of frequent changes in presbyopic glasses. 5. Patients develop delayed dark adaptation, a disability which becomes increasingly disturbing in the later stages. Signs I. Anterior segment signs. Ocular examination including slit-lamp biomicroscopy may reveal normal anterior segment. In late stages pupil reflex becomes sluggish and cornea may show slight haze. II. Intraocular pressure changes. In the initial stages the IOP may not be raised permanently, but there is an exaggeration of the normal diurnal variation. Therefore, repeated observations of IOP (every 3-4 hour), for 24 hours is required during this stage (Diurnal variation test). In most patients IOP falls during the evening, contrary to what happens in closed angle glaucoma. Patterns of diurnal variation of IOP are shown in Fig. 9.8. A variation in IOP of over 5 mm Hg (Schiotz) is suspicious and over 8 mm of Hg is diagnostic of glaucoma. In later stages, IOP is permanently raised above 21 mm of Hg and ranges between 30 and 45 mm of Hg. Fig. 9.8. Patterns of diurnal variations of IOP: A, normal slight morning rise; B, morning rise seen in 20% cases of POAG; C, afternoon rise seen in 25% cases of POAG; D, biphasic variation seen in 55% cases of POAG. 216 Comprehensive OPHTHALMOLOGY 2. Thinning of neuroretinal rim which occurs in advanced cases is seen as a crescentric shadow adjacent to the disc margin. 3. Nasal shifting of retinal vessels which have the appearance of being broken off at the margin is an important sign (Bayonetting sign). When the edges overhang, the course of the vessels as they climb the sides of the cup is hidden. 4. Pulsations of the retinal arterioles may be seen at the disc margin (a pathognomic sign of glaucoma), when IOP is very high. 5. Lamellar dot sign the pores in the lamina cribrosa are slit-shaped and are visible up to the margin of the disc. (c) Glaucomatous optic atrophy. As the damage progresses, all the neural tissue of the disc is destroyed and the optic nerve head appears white and deeply excavated (Figs. 9.10 C&D). Pathophysiology of disc changes. Both mechanical and vascular factors play a role in the cupping of the disc. Mechanical effect of raised IOP forces the lamina cribrosa backwards and squeezes the nerve fibres within its meshes to disturb axoplasmic flow. Vascular factors contribute in ischaemic atrophy of the nerve fibres without corresponding increase of supporting glial tissue. As a result, large caverns or lacunae are formed (cavernous optic atrophy). IV. Visual field defects. Visual field defects usually run parallel to the changes at the optic nerve head and continue to progress if IOP is not controlled. These can be described as early and late field defects. Anatomical basis of field defects. For better understanding of the actual field defects, it is mandatory to have a knowledge of their anatomical basis. (A) Distribution of retinal nerve fibres (Fig. 9.11). 1. Fibres from nasal half of the retina come directly to the optic disc as superior and inferior radiating fibres (srf and irf). 2. Those from the macular area come horizontally as papillomacular bundle (pmb). 3. Fibres from the temporal retina arch above and below the macula and papillomacular bundle as superior and inferior arcuate fibres with a horizontal raphe in between (saf and iaf). III. Optic disc changes. Optic disc changes, usually observed on routine fundus examination, provide an important clue for suspecting POAG. These are typically progressive, asymmetric and present a variety of characteristic clinical patterns. It is essential, therefore, to record the appearance of the nerve head in such a way that will accurately reveal subtle glaucomatous changes over the course of follow-up evaluation. Examination techniques. Careful assessment of disc changes can be made by direct ophthalmoscopy, slitlamp biomicroscopy using a + 90D lens, Hruby lens or Goldmann contact lens and indirect ophthalmoscopy. The recording and documentation techniques include serial drawings, photography and photogrammetry. Confocal scanning laser topography (CSLT) i.e., Heidelberg retinal tomograph (HRT) is an accurate and sensitive method for this purpose. Other advanced imaging techniques include optical coherence tomography (OCT) and scanning laser polarimetry i.e., Nerve fibre analyser (NFA). Glaucomatous changes in the optic disc can be described as early changes, advanced changes and glaucomatous optic atrophy. Figures 9.9A & B show normal disc configuration. (a) Early glaucomatous changes (Figs. 9.9C&D) should be suspected to exist if fundus examination reveals one or more of the following signs: 1. Vertically oval cup due to selective loss of neural rim tissue in the inferior and superior poles. 2. Asymmetry of the cups. A difference of more than 0.2 between two eyes is significant. 3. Large cup i.e., 0.6 or more (normal cup size is 0.3 to 0.4) may occur due to concentric expansion. 4. Splinter haemorrhages present on or near the optic disc margin. 5. Pallor areas on the disc. 6. Atrophy of retinal nerve fibre layer which may be seen with red free light. (b) Advanced glaucomatous changes in the optic disc (Figs. 9.10A&B): 1. Marked cupping (cup size 0.7 to 0.9), excavation may even reach the disc margin, the sides are steep and not shelving (c.f. deep physiological cup). GLAUCOMA 217 Fig. 9.9. Normal optic disc (A, Diagrammatic depiction; B, Fundus photograph) and optic disc showing early glaucomatous changes (C, Diagrammatic depiction; D, Fundus photograph). B A D C (B) Arrangement of nerve fibres within optic nerve head (Fig. 9.12): Those from the peripheral part of the retina lie deep in the retina but occupy the most peripheral (superficial) part of the optic disc. While fibres originating closer to the nerve head lie superficially in the retina and occupy a more central (deep) portion of the disc. The arcuate nerve fibres occupy the superior and inferior temporal portions of optic nerve head and are most sensitive to glaucomatous damage; accounting for the early loss in the corresponding regions of the visual field. Macular fibres are most resistant to the glaucomatous damage and explain the retention of the central vision till end. 218 Comprehensive OPHTHALMOLOGY Fig. 9.10. Optic disc showing advanced glaucomatous changes (A, diagramatic depiction; B, fundus photograph) and glaucomotous optic atrophy (C, diagramatic depiction; D, fundus photograph). Progression of field defects. Visual field defects in glaucoma are initially observed in Bjerrum’s area (10- 25 degree from fixation) and correlate with optic disc changes. The natural history of the progressive glaucomatous field loss, more or less, takes the following sequence: 1. Isopter contraction. It refers to mild generalised constriction of central as well as peripheral field. It is the earliest visual field defect occurring in A C glaucoma. However, it is of limited diagnostic value, as it may also occur in many other conditions. 2. Baring of blind spot. It is also considered to be an early glaucomatous change, but is very non-specific and thus of limited diagnostic value. Baring of the blind spot means exclusion of the blind spot from the central field due to inward curve of the outer boundary of 30° central field (Fig. 9.13A). B D GLAUCOMA 219 Fig. 9.11. Distribution of retinal nerve fibres. Fig. 9.12. Arrangement of nerve fibres within optic nerve head. Fig. 9.13. Field defects in POAG: A, baring of blind spot; B, superior paracentral scotoma; C, Seidel's scotoma; D, Bjerru-m's scotoma; E, double arcuate scotoma and Roenne's central nasal step. 3. Small wing-shaped paracentral scotoma (Fig. 9.13B). It is the earliest clinically significant field defect. It may appear either below or above the blind spot in Bjerrum's area (an arcuate area extending above and below the blind spot to between 10o and 20o of fixation point). 4. Seidel’s scotoma.With the passage of time paracental scotoma joins the blind spot to form a sickle shaped scotoma known as Seidel’s scotoma (Fig. 9.13C). 5. Arcuate or Bjerrum’s scotoma. It is formed at a later stage by the extension of Seidel’s scotoma in an area either above or below the fixation point to reach the horizontal line (Fig. 9.13D). Damage to the adjacent fibres causes a peripheral breakthrough. 6. Ring or double arcuate scotoma. It develops when the two arcuate scotomas join together (Fig. 9.13E). 7. Roenne's central nasal step. It is created when the two arcuate scotomas run in different arcs and meet to form a sharp right-angled defect at the horizontal meridian (Fig. 9.13E). 220 Comprehensive OPHTHALMOLOGY 8. Peripheral field defects. These appear sometimes at an early stage and sometimes only late in the disease. The peripheral nasal step of Roenne's results from unequal contraction of the peripheral isopter. 9. Advanced glaucomatous field defects. The visual field loss gradually spreads centrally as well as peripherally, and eventually only a small island of central vision (tubular vision) and an accompanying temporal island are left. With the continued damage, these islands of vision also progressively diminish in size until the tiny central island is totally extinguished. The temporal island of the vision is more resistant and is lost in the end leaving the patient with no light perception. Diagnosis of glaucoma field defects on HFA single field printout. Glaucomatous field defects should always be interpreted in conjunction with clinical features (IOP and optic disc changes). Further, before final interpretation, the fields must be tested twice, as there is often a significant improvement in the field when plotted second time (because patients become more familiar with the machine and test process). Criteria to grade glaucomatous field defects. The criteria to label early, moderate and severe glaucomatous field defect from the HFA central 30-2 test, single printout is depicted in Table 9.2. Note. For proper understanding of Table 9.2, evaluation of the Humphrey single field printout described on page 485 should be revised. Ocular associations POAG may sometimes be associated with high myopia, Fuchs’ endothelial dystrophy, retinitis pigmentosa, central retinal vein occlusion and primary retinal detachment. INVESTIGATIONS 1. Tonometry. Applanation tonometry should be preferred over Schiotz tonometry (see page 479). 2. Diurnal variation test is especially useful in detection of early cases (see page 215). 3. Gonioscopy. It reveals a wide open angle of anterior chamber. Its primary importance in POAG is to rule out other forms of glaucoma. For details (see page 206 and 546). 4. Documentation of optic disc changes is of utmost importance (see page 216). 5. Slit-lamp examination of anterior segment to rule out causes of secondary open angle glaucoma. 6. Perimetry to detect the visual field defects. 7. Nerve fibre layer analyzer (NFLA) is a recently introduced device which helps in detecting the Table 9.2: Criteria to diagnose early, moderate and severe glaucomatous field defects from HFA: 30-2- test. Sr. Parameter Criteria for glaucomatous field defects no. Early defects Moderate defects Severe defects 1. Mean deviation (MD) <– 6 dB – 6dB – 12 dB > – 12dB 2. Corrected pattern Depressed to the p<5% Depressed to the p <5% Depressed to the p<5% standard deviation (CPSD) 3. Pattern deviation plot Points depressed < 18 (25%) < 37 (50%) > 37 (>50%) below the p < 5% or Points depressed < 10 < 20 > 20 below the p < 1% 4. Glaucoma Hemifield Outside normal limits Outside normal limits Outside normal limits Test (GHT) 5. Sensitivity in central No point < 15dB One hemifield may have Both hemifield have 5 degree point with sensitivity points with sensitivity <15dB <15dB No point has 0 dB Any point has 0 dB GLAUCOMA 221 glaucomatous damage to the retinal nerve fibres before the appearance of actual visual field changes and/or optic disc changes. 8. Provocative tests are required in border-line cases. The test commonly performed is water drinking test. Other provocative tests not frequently performed include combined water drinking and tonography, bulbar pressure test, prescoline test and caffeine test. Water drinking test. It is based on the theory that glaucomatous eyes have a greater response to water drinking. In it after an 8 hours fast, baseline IOP is noted and the patient is asked to drink one litre of water, following which IOP is noted every 15 min. for 1 hour. The maximum rise in IOP occurs in 15-30 min. and returns to baseline level after 60 minutes in both normal and the glaucomatous eyes. A rise of 8 mm of Hg or more is said to be diagnostic of POAG. DIAGNOSIS Depending upon the level of intraocular pressure (IOP), glaucomatous cupping of the optic disc and the visual field changes (Fig. 9.14) the patients are assigned to one of the following diagnostic entities: 1. Primary open angle glaucoma (POAG). Characterstically POAG is labelled when raised IOP (>21 mm of Hg) is associated with definite glaucomatous optic disc cupping and visual field changes. However, patients with raised IOP and either typical field defects or disc changes are also labelled as having POAG. 2. Ocular hypertension or glaucoma suspect. Either of these terms is used when a patient has an IOP constantly more than 21 mm of Hg but no optic disc or visual field changes (for details see page 224). 3. Normal tension glaucoma (NTG) or low tension glaucoma (LTG) is diagnosed when typical glaucomatous disc cupping with or without visual field changes is associated with an intraocular pressure constantly below 21 mm of Hg (For details see page 224). MANAGEMENT General considerations Baseline evaluation and grading of severity of glaucoma. The aim of treatment is to lower intraocular pressure to a level where (further) visual loss does not occur. The management thus requires careful and regular periodic supervision by an ophthalmologist. Therefore, it is important to perform a good baseline examination with which future progress can be compared. The initial data should include: visual acuity, slit-lamp examination of anterior segment, tonometry (preferably with applanation tonometer); optic disc evaluation (preferably with fundus photography), gonioscopy and visual field charting. American Academy of Ophthalmology (AAO) grades severity of glaucoma damage into mild, moderate and severe (Table 9.3). Table 9.3: Severity of glaucoma damage Degree Description Mild Characteristic optic-nerve abnormalities are consistent with glaucoma but with normal visual field. Moderate Visual-field abnormalities in one hemi-field and not within 5 degrees of fixation. Severe Visual-field abnormalities in both hemifields and within 5 degrees of fixation. Source : AAO 2000a Fig. 9.14. Triad of abnormalities in disc, field and intraocular pressure (IOP) for the diagnosis of glaucoma. 222 Comprehensive OPHTHALMOLOGY Therapeutic choices include: Medical therapy, Argon or diode laser trabeculoplasty, and Filteration surgery. A. Medical therapy The initial therapy of POAG is still medical, with surgery as the last resort. Antiglaucoma drugs available are described in detail on pages 423-427. Basic principles of medical therapy of POAG 1. Identification of target pressure. From the baseline evaluation data a ‘target pressure’ (below which glaucomatous damage is not likely to progress) should be identified for each patient. The target pressure is identified taking into account the severity of existing damage, the level of IOP, age, and general health of the patient. Although it is not possible to predict the safe level of IOP, however, progression is uncommon if IOP is maintained at less than 16 to 18 mm of Hg in patients having mild to maderate damage. Lower target pressures (12-14 mmHg) are required in patients with severe damage. 2. Single drug therapy. One topically instilled antiglaucoma drug should be chosen after due consideration to the patient’s personal and medical factors. If the initial drug chosen is ineffective or intolerable, it should be replaced by the drug of second choice. 3. Combination therapy. If one drug is not sufficient to control IOP then a combination therapy with two or more drugs should be tried. 4. Monitoring of therapy by disc changes and field changes and tonometry is most essential on regular follow-up. In the event of progress of glaucomatous damage the target pressure is reset at a lower level. Treatment regimes. There are no clear-cut prescribed treatment regimens for medical therapy of POAG. However, at present considerations are as follows : I. Single drug therapy 1. Topical beta-blockers are being recommended as the first drug of choice for medical therapy of POAG in poors and average income patients. These lower IOP by reducing the aqueous secretion due to their effect on beta - receptors in the ciliary processes. Preparations. In terms of effectiveness, there is little difference between various beta-blockers. However, each offers a slight advantage over the other, which may help in choosing the particular medication as follows: Timolol maleate (0.25, 0.5% : 1-2 times/day) is most popular as initial therapy. However, it should not be used in patients having associated bronchial asthma and/or heart blocks. Betaxolol (0.25% : 2 times/day). Being a selective beta-1 blocker it is preferred as initial therapy in patients with cardiopulmonary problems. Levobunolol (0.25, 0.5% : 1-2 times/day). Its action lasts the longest and so is more reliable for once a day use than timolol. Carteolol (1%: 1-2 times/day). It raises triglycerides and lowers high density lipoproteins the least. Therefore, it is the best choice in patients with POAG having associated hyperlipidemias or atherosclerotic cardiovascular disease. 2. Pilocarpine (1, 2, 4%: 3-4 times/day). It is a very effective drug and had remained as the sheet anchor in the medical management of POAG for a long time. However, presently it is not being preferred as the first drug of choice or even as second choice. It is because of the fact that in younger patients it causes problems due to spasm of accommodation and miosis. Most, but not all, older patients tolerate pilocarpine very well; however, axial lenticular opacities when present precludes its use in many such patients. Therefore, presently pilocarpine is being considered only as an adjunctive therapy where other combinations fail and as second choice in poor patients. Mechanism of action. Pilocarpine contracts longitudinal muscle of ciliary body and opens spaces in trabecular meshwork, thereby mechanically increasing aqueous outflow. 3. Latanoprost (0.005%: once daily). It is a prostaglandin by nature and decreases the IOP by increasing the uveo-scleral outflow of aqueous. Presently, it is being considered the drug of first choice for the treatment of POAG (provided patient can afford to buy it). Therefore, it is a very good GLAUCOMA 223 adjunctive drug to beta-blockers, dorzolamide and even pilocarpine when additional therapy is indicated. 4. Dorzolamide (2%: 2-3 times/day). It is a recently introduced topical carbonic anhydrase inhibitor which lowers IOP by decreasing aqueous secretion. It has replaced pilocarpine as the second line of drug and even as an adjunct drug. 5. Adrenergic drugs. Role in POAG is as follows: i. Epinephrine hydrochloride (0.5, 1, 2%: 1-2 times/ day) and dipivefrine hydrochloride (0.1%: 1-2 times/day). These drugs lower the IOP by increasing aqueous outflow by stimulating beta recepters in the aqueous outflow system. These are characterized by a high allergic reaction rate. Their long-term use has also been recognized as a risk factor for failure of filtration glaucoma surgery. For these reasons, epinephrine compounds are no longer being used as first line or second line drug. However, dipivefrine may be combined with beta-blockers in patients where other drugs are contraindi-cated. ii. Brimonidine (0.2% : 2 times/day). It is a selective alpha-2-adrenergic agonist and lowers IOP by decreasing aqueous production. Because of increased allergic reactions and tachyphylaxis rates it is not considered the drug of first choice in POAG. It is used as second drug of choice and also for combination therapy with other drugs. II. Combination topical therapy If one drug is not effective, then a combination of two drugs—one drug which decreases aqueous production (timolol or other betablocker, or brimonidine or dorzolamide) and other drug which increase aqueous outflow (latanoprost or brimonidine or pilocarpine) may be used. III. Role of oral carbonic anhydrase inhibitors in POAG Acetazolamide and methazolamide are not recommended for long-term use because of their sideeffects. However, these may be added to control IOP for short term. B. Argon or diode laser trabeculoplasty (ALT or DLT) It should be considered in patients where IOP is uncontrolled despite maximal tolerated medical therapy. It can also be considered as primary therapy where there is non-compliance to medical therapy. Technique and role of ALT in POAG. It has an additive effect to medical therapy. Its hypotensive effect is caused by increasing outflow facility, possibly by producing collagen shrinkage on the inner aspect of the trabecular meshwork and opening the intratrabecular spaces. It has been shown to lower IOP by 8-10 mm of Hg in patients on medical therapy and by 12-16 mm in patients who are not receiving medical treatment. The treatment regime usually employed consists of 50 spots on the anterior half of the trabecular meshwork over 180°. Complications. These include transient acute rise of IOP, which can be prevented by pretreatment with pilocarpine and/or acetazolamide; and inflammation which can be lessened by use of topical steroids for 3-4 days. Less commonly haemorrhage, uveitis, peripheral anterior synechiae and reduced accommodation may occur. C. Surgical therapy Indications 1. Uncontrolled glaucoma despite maximal medical therapy and laser trabeculoplasty. 2. Non-compliance of medical therapy and nonavailability of ALT. 3. Failure with medical therapy and unsuitable for ALT either due to lack of cooperation or inability to visualize the trabeculum. 4. Eyes with advanced disease i.e., having very high IOP, advanced cupping and advanced field loss should be treated with filtration surgery as primary line of management. 5. Recently, some workers are even recommending surgery as primary line of treatment in all cases. Types of surgery Surgical treatment of POAG primarily consists of a fistulizing (filtration) surgery which provides a new channel for aqueous outflow and successfully controls the IOP (below 21 mm of Hg). Trabeculectomy is the most frequently performed filtration surgery now-a-days. The details of filtration operations are described on page 237.
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