28

The Use of Special Tests in Narrow-Angled Eyes

Joel S. Schuman, MD, FACS; Rachel L. Anderson, MD; and David L. Epstein, MD, MMM

Surgical iridectomy carried significant risk, and prior to performing iridectomy a high degree of certainty was required as to the likelihood of angle closure in any given eye, necessitating special tests as to that possibility. The advent of laser iridectomy, with its favorable risk/benefit considerations, resulted in a clinical situation in which additional special tests are only rarely performed in eyes with potentially occludable angles. However, a firm understanding of the principles involved in evaluating these eyes is useful (see Chapter 23). These special tests are detailed not only because of their historical importance, but also because they reinforce the understanding of principles that are critical to appropriately treating such eyes. The beginning resident or student is urged to read and understand the conceptual basis for such tests.

GONIOSCOPY AND TONOGRAPHY

Reliable diagnosis of angle closure can only be made by gonioscopy, but tonography may be extremely helpful. In the early stages, if the patient is examined during an interval of normal intraocular pressure (IOP), one finds the angle open throughout, but at least a portion of the angle is very narrow. Under these conditions, tonography indicates a normal facility of outflow. During an interval of moderately elevated IOP, one finds that a portion of the angle appears closed, and tonography shows a proportionate decrease in facility of outflow. The significance of the tonographic measurements is that the change in facility of outflow is dependent on whether the angle is open or closed and is independent of current IOP. If open-angle glaucoma were present with the angle open and the IOP in a normal phase, the tonographic measurement would show persistently subnormal facility of aqueous outflow (and the implication would be that the IOP was normal due to a diurnal phase of decreased aqueous humor formation).

Sometimes, the situation is complicated at the initial examination because the patient may have started to take miotic treatment prescribed elsewhere. If there are no synechiae, the findings under the influence of miotic treatment may be the same as during a spontaneous remission: the IOP normal, angle open throughout, and facility of outflow normal. In such a case, to establish the diagnosis, all treatment is discontinued in the hope that IOP will increase considerably. Then, gonioscopy is repeated during the period of elevated IOP. If, with the IOP elevated, the angle is still entirely open, the diagnosis must be open-angle glaucoma, despite the narrow angle. If, on the other hand, one finds an extent of angle closure consistent with the elevation of IOP (see Chapters 7 and 23), the diagnosis is angle-closure glaucoma.

If, on discontinuation of treatment, IOP increases only moderately, such as to the high 20s, there is much more difficulty in making a diagnosis than cases in which the IOP goes to 40 or 50 mm Hg. Very little closure is necessary to cause an increase of IOP to the high 20s, and every gonioscopist realizes how difficult it may be to distinguish whether a small portion of the angle is closed or almost closed. During a period without treatment, with IOP at the general level of mid- to high 20s, tonography may be helpful, although often not decisive. In this IOP range in angle-closure glaucoma, one finds a C value only 20% or 30% below normal. A considerably poorer C value, with the IOP in this range, suggests the presence of open-angle glaucoma. In such equivocal cases, the darkroom test, the bright light test with or without thymoxamine, or possibly the mydriasis test may be helpful.

DARKROOM PRONE TESTS

The darkroom test is performed by having the patient remain in the dark, awake, for 1 hour, preferably face down.^1,2 This can be accomplished by having the patient sitting in a chair with his or her head resting on his or her arms on an adjacent table, taking care not to press on the eyes. Immediately at the end of this period, the IOP is measured. In a negative test, IOP in both eyes is almost exactly the same as before the test and the same in both eyes. One may ordinarily think of a positive darkroom test as a situation in which IOP in one or both eyes increases considerably, to a level of 40 or 50 mm Hg or more, but instances of such considerable increases after 1 hour in the dark are uncommon. It is much more common to find an increase of only 5 to 10 mm Hg. Because in a negative darkroom test, in patients who have no glaucoma of any sort, the IOP is usually exactly the same as before the test, an increase of only a few millimeters of mercury may be significant. If in the darkroom test there is a significant difference in the increase in IOP in the 2 eyes, even though the increase is moderate, this should be interpreted as a positive darkroom test. Due to its duration, a darkroom prone test may be inconvenient for practical clinical use. Unfortunately, recent evidence suggests that a modified darkroom prone test of just 15 minutes is not effective for differentiating primary angle closure suspects from open-angle controls.³

However, a positive darkroom test based only on IOP change can occur in cases of open-angle glaucoma when a diurnal IOP increase happens to coincide with the test. Unless the increase of IOP is large and associated with a gonioscopically closed angle, other types of tests may be required to be sure.

Interestingly, darkroom tests may predict structural characteristics of certain eyes. A study of family members of patients with known primary angle closure glaucoma found that persons with a positive darkroom prone provocative test had significantly shallower anterior chambers, significantly thicker lenses, and significantly shorter axial length than persons with borderline or negative darkroom tests.⁴

If the darkroom test is completely negative, does this rule out angle-closure glaucoma in a given case? A negative darkroom test does not rule out angle-closure glaucoma.⁵ If the angle is thought to be dangerously narrow and the darkroom test is negative, in the past (before the advent of laser iridectomy), we recommended that the patient have an IOP check twice a year indefinitely and repeat the darkroom test once or twice a year, for one cannot predict if and when such angles may close. Some patients were evaluated for 12 or more years, remaining normal and asymptomatic. Yet, in other cases, the tests became positive in a few years or less, as in the following example.

Case 28-1

In this patient, the angles were extremely narrow, but IOP was normal and the darkroom test negative. IOP was checked regularly twice a year; it remained around 17 mm Hg, and the patient was asymptomatic. Finally, at a visit 6.5 years after the initial visit, IOP was right 22 mm Hg and left 27 mm Hg. The patient was still asymptomatic. A darkroom test was performed, and IOP increased to 28 mm Hg in the right eye and 45 mm Hg in the left. A peripheral iridectomy was done on both eyes.

David Hill, MD conducted a survey of patients who underwent periodic darkroom tests in the Glaucoma Service of the Massachusetts Eye and Ear Infirmary purely because of extremely narrow angles. This survey indicated that, after a negative darkroom test, a patient was unlikely to develop acute angle closure within the next 6 months.

However, shortcomings of the darkroom test include the following:

• It is often negative even though the eye may be subject to spontaneous subacute angle-closure attacks.³
  
• It is difficult to perform gonioscopy as part of the test without causing some miosis with the light that is necessary for gonioscopy, and this may cause the angle to open even though it may have been closed previously in the dark. (We have performed gonioscopy in the dark with an infrared converter to get around this difficulty, but have found it difficult to evaluate the angle with the monochromatic, 2-dimensional image obtained.)
  
• An increase in IOP in the dark occurs in some open-angle glaucomatous eyes, sometimes as a coincidental part of spontaneous diurnal fluctuation, and this may cause error of interpretation unless the gonioscopy is done carefully and critically.

The bright light and thymoxamine test6,7 is the opposite of the darkroom test. The patient is placed under bright illumination to induce and maintain miosis, to favor opening of the angle. Accommodation is purposely avoided either by using diffuse illumination or by using a light source very close to the eye. (Perhaps application of plus lenses would be a worthwhile refinement.) The aim is to induce the pupillary sphincter to constrict, but to avoid constriction of the ciliary muscle, so that there will be no complicating alteration of the lens or the trabecular meshwork by the ciliary muscle.

The opening of the angle can be aided considerably by applying 0.5% thymoxamine hydrochloride eye drops in combination with exposure to bright light.⁶ Thymoxamine is an alpha-adrenergic blocking agent that temporarily causes the radial muscle fibers of the iris to relax and allows the pupillary sphincter muscle to act unopposed in constricting the pupil and pulling the iris away from the angle wall. Thymoxamine does not appreciably affect the ciliary muscle, and if the angle is already open, it does not influence IOP or facility of aqueous outflow.⁷ (In this respect, light and thymoxamine are unlike pilocarpine or cholinergic miotics, which are not well suited for use in testing for angle closure because they cause contraction of both the pupil and the ciliary muscle. By both mechanisms, pilocarpine and cholinergic miotics can influence IOP and aqueous outflow so that they do not serve to distinguish clearly between angle-closure and open-angle glaucoma, as they normalize IOP and outflow in both conditions.) Thymoxamine should be administered to only one eye, and the other eye should be used as a control for diurnal variation.

One precaution to observe in the use of the bright light test with or without thymoxamine is to avoid subjecting the eye to drying under the influence of local anesthesia and its attendant reduction in blink rate. The only shortcoming of the bright light test and thymoxamine is that, in some eyes, the miosis induced is not enough to open the angle and lower the IOP; however, where it is positive, this test gives clear, uncomplicated evidence.

When should one perform the darkroom test and when the bright light and thymoxamine test? In patients with narrow angles but normal IOP, the question is whether this narrow, but presumably still functionally open, angle is capable of spontaneous closure. Such a patient should have a darkroom test to answer this question. However, in patients with narrow angles but elevated IOP, there is a separate question: Is the IOP elevation that is already present due to partial angle closure? For this question, the thymoxamine bright light test should be performed first. This test, by inducing miosis, can reverse appositional (but not synechial) angle closure and lower IOP. Because the IOP is already elevated possibly due to an open-angle component, the potential for diurnal fluctuation due to open-angle glaucoma (and a spurious increase of IOP in the dark) must be kept in mind. This is further reason why a unilateral IOP lowering due to thymoxamine may be more definitive and why the latter test should be performed initially in such patients.

The mydriasis test, which we have never favored (see Chapter 23), is performed by applying a short-acting mydriatic, such as eucatropine, homatropine, cyclopentolate, or phenylephrine, with measurement of IOP and inspection of the angle when the pupil has dilated, to determine if the angle has become closed. In many cases, the test may have been considered negative at the stage of widest mydriasis, and the patient had been dismissed to go home, with or without application of a counteracting drop of pilocarpine. After a few hours, the angle unexpectedly closed and an acute attack developed. This has had unfortunate consequences for patients who did not understand what was happening or who did not promptly obtain treatment for their condition.

The mydriasis test has many disadvantages. It is less natural and physiologic than the darkroom or bright light test. It is often negative in eyes that are subject to actual spontaneous episodes of subacute angle closure, yet it can cause closure of narrow angles that might never close spontaneously. It is otherwise treacherous in that it may belatedly induce an angle-closure attack and, for greatest safety, would require surveillance of the patient for many hours. In certain cases of open-angle glaucoma,^8,9 cycloplegic mydriatics can cause an increase of IOP by impairment of facility of aqueous outflow without closure of the angle, necessitating careful, critical gonioscopy to minimize the chances of misinterpretation of an IOP increase with this test. If adrenergic mydriatics are used, it must be remembered that they have potentially confusing side effects, reducing aqueous formation in some eyes and, in rare instances, causing an increase of IOP in open-angle glaucomatous eyes without causing the angle to close, possibly from pigment particle liberation¹⁰ (see Chapter 22).

Therefore, we rarely perform the mydriatic test to diagnose angle-closure glaucoma. However, as discussed in Chapter 26, we routinely perform a phenylephrine provocative test after laser iridectomy to rule out a plateau iris syndrome and establish baseline parameters for future evaluation.

Mapstone¹¹ proposed that phenylephrine combined with pilocarpine might be useful as a provocative test for angle closure, but long-term observation has not substantiated this theory.¹²

REFERENCES

1.      Hyams SW, Friedman Z, Neumann E. Elevated intraocular pressure in the prone position. A new provocative test for angle-closure glaucoma. Am J Ophthalmol. 1968;66:661-672.

2.      Friedman Z, Neumann E. Comparison of prone-position, darkroom, and mydriatic tests for angle-closure glaucoma before and after peripheral iridectomy. Am J Ophthalmol. 1972;74:24-27.

3.      Friedman DS, Chang DS, Jiang Y, et al. Darkroom prone provocative testing in primary angle closure suspects and those with open angles. Br J Ophthalmol. 2019;103:i-ii.

4.      Sihota R, Mohan S, Dada T, et al. An evaluation of the darkroom prone provocative test in family members of primary angle closure glaucoma patients. Eye (Lond). 2007;21(7):984-989.

5.      Wilensky JT, Kaufman PL, Frohlichstein D, et al. Follow-up of angle-closure glaucoma suspects. Am J Ophthalmol. 1993;115:338-346.

6.      Wand M, Grant WM. The thymoxamine test: a test to differentiate angle-closure glaucoma from open-angle glaucoma with narrow angles. Arch Ophthalmol. 1978;96:1009-1011.

7.      Wand M, Grant WM. Thymoxamine hydrochloride: effects on the facility of outflow and intraocular pressure. Invest Ophthalmol. 1976;15:400-403.

8.      Harris LS, Galin MA. Cycloplegic provocative testing. Arch Ophthalmol. 1969;81:544-547.

9.      Harris LS, Galin MA, Mittag TW. Cycloplegic provocative testing and topical administration of steroids. Arch Ophthalmol. 1971;86:12-14.

10.    Epstein DL, Boger WP, Grant WM. Phenylephrine provocative testing in the pigmentary dispersion syndrome. Am J Ophthalmol. 1978;85:43-50.

11.    Mapstone R. Outflow changes in positive provocative tests. Br J Ophthalmol. 1977;61:634-636.

12.    Wishart PK. Can the pilocarpine phenylephrine provocative test be used to detect covert angle closure? Br J Ophthalmol. 1991;75:615-618.