From the Bascom Palmer Eye Institute (CSM, MEB, FE, RKL), University of Miami Miller School of Medicine Miami, Florida; Delray Eye Associates (MW), Delray Beach, Florida; and Boston Medical Center (MAD), Boston University School of Medicine, Boston, Massachsetts.
R.K. Lee is supported by NIH grant EY016775. The Bascom Palmer Eye Institute is supported by an unrestricted grant from Research to Prevent Blindness (New York, New York), the Strobis Glaucoma Foundation (Boca Raton, FL), and NIH Center Grant P30-EY014801.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Richard K. Lee, MD, PhD, Bascom Palmer Eye Institute, U. of Miami Miller School of Medicine, 900 N.W. 17th Street, Miami, FL 33136.
Pseudoexfoliation (PXF) is the most common identifiable cause of secondary open angle glaucoma.1,2 Pseudoexfoliation is characterized by slit lamp visualization of white, dandruff-like flakes of PXF material deposited on ocular and in systemic tissues. The primary morbidity from deposition of PXF material is ocular with PXF being associated with increased risk for development of cataract, ocular hypertension, glaucoma, and increased operative complications during cataract extraction.
Pseudoexfoliation is also associated with narrow angles and secondary angle closure glaucoma. The incidence of angle closure glaucoma in individuals with PXF is increased.3–8 The incidence of occludable angles appears to range from 6 to 18% and the incidence of angle closure per meta-analyses appears to be approximately 2.2%.8 The reasons for this increased incidence of narrow angles and pupillary block angle closure glaucoma have not been well characterized in the literature. Herbst9 in 1976 reported on a case of acute angle closure where the pupillary block was attributed to pseudoexfoliative matter promoting increased iridolenticular adhesions. Gohdo et al.10 more recently demonstrated acute angle closure by UBM in an individual with PXF, which was attributable to zonular laxity and anterior subluxation of the lens. Aside from these few case reports, further work to document this phenomenon and understand its pathophysiology remains to be carried out. This case report and its review of the literature with its documented treatment outcomes describes and demonstrates the mechanism of angle closure observed in PXF.
The following is a case of subacute pupillary block resulting in acute angle closure glaucoma attributed to zonular laxity caused by PXF, as demonstrated by UBM and slit lamp examination. Progressive zonular laxity secondary to pseudoexfoliation-associated degeneration of the zonules led to narrow angles and increased proximity of the pupillary border to the lens capsule. Over time, synechiae formed between the pupillary border and the lens capsule pulling the lens capsule forward leading to pupillary block glaucoma and further shallowing of the anterior chamber with iris bombé. The pupillary block glaucoma was broken by performing a peripheral laser iridotomy with significant deepening of the anterior chamber depth. The anterior chamber was then further deepened by breaking pupillary synechiae with a mydriatic, freeing the iris from the lens capsule and allowing the lens-zonular diaphragm to return to a more posterior position. Patients with PXF need routine gonioscopic and anterior segment examination of the anterior chamber depth to observe for an increased risk of angle closure glaucoma. Prophylactic placement of laser peripheral iridotomies in PXF eyes with narrow angles and shallow anterior chamber depths may minimize the risk of pupillary block glaucoma.
A 75-year-old man was referred to the glaucoma service at the Bascom Palmer Eye Institute for evaluation and treatment of angle closure glaucoma. The patient noticed progressively decreased and foggy vision for a period of 3 to 4 weeks prior to presentation. He especially noticed the blurry vision when reading and felt the symptoms were more apparent in the right eye. He denied any ocular pain or redness but complained of intermittent headache and dizziness. He denied prior ocular trauma, history of glaucoma, strabismus, or amblyopia.
His past medical and surgical history was notable for hyperlipidemia and prostate cancer, for which he had undergone a radical prostatectomy. He also had a history of polio, which left him with a shorter and weaker right lower extremity. The patient denied any family history of glaucoma or blindness. He also denied any use of alcohol, tobacco, or use of illicit drugs. He had no known drug allergies. He did not use any ocular medications and was otherwise on Crestor® (©AstraZeneca Pharmaceuticals LP, Sweden) and started on Zetia® (©Merck/Schering-Plough Pharmaceuticals, Whitehouse Station, N.J. & Kenilworth, N.J.) within the past month. He otherwise had not been on any other new systemic medications in the prior month.
Examination in the clinic revealed a best-corrected visual acuity of 20/25 (−1.75+0.50 x 050) right eye (OD) and 20/20 (−0.75+0.50 x 125) left eye (OS) with a relative myopic shift OD; the patient had forgotten his spectacles. Motility and confrontational visual fields were within normal limits. No relative afferent pupillary defect was noted. Intraocular pressures (IOP) by Goldmann applanation were 24 mm Hg OD and 17 mm Hg OS. Slit lamp examination was notable for clear corneas bilaterally as well as quiet anterior chambers. The anterior chamber depth, however, was significantly more narrow in the right eye relative to the left eye (see Fig. 1). The iris was in a bombé configuration in the right eye, with a normal iris contour in the left eye (see Fig. 1). The pupil margin revealed loss of the pupillary ruff and the presence of white flakes consistent with PXF material in both eyes. PXF material was present on the anterior lens capsule. The lenses had relatively similar 1–2+ nuclear sclerotic cataracts in both eyes. Gonioscopy demonstrated a narrow angle in the right eye with no visible angle structures; the left eye was open to the scleral spur 360° without peripheral anterior synechiae (PAS) (see Fig. 2). The angle opened with indentation gonioscopy in the right eye to the scleral spur and no PAS was observed.
Figure 1. Slit Lamp Photo Demonstrating a Significantly More Narrow Anterior Chamber Depth in the Right (top) Relative to the Left Eye (bottom). Also Note the Iris Bombé Configuration on the Right Eye and Absence of Such a Configuration in the Left Eye.
Figure 2. Gonioscopic View of the Superior Angle in the Right Eye (top) when Compared with the Left Eye (bottom). Note the Absence of Visible Structures in the Right Eye Angle (top).
The finding of asymmetric intraocular pressure with corresponding asymmetric anterior chamber depth and an iris bombé configuration in the right eye were consistent with appositional angle closure and pupillary block glaucoma. The etiology did not appear to be pharmacologic based on the history, and no ciliary body swelling or rotation was noted by UBM. Moreover, the angle in the left eye was not anatomically narrow. The normal appearing angle in the left eye and myopic shift in the right eye made a phacomorphic etiology plausible though the lenses had similar appearing cataractous changes bilaterally. Another plausible explanation was anterior subluxation of the lens secondary to zonular laxity from the underlying PXF leading to pupillary block. This etiology would also be consistent with myopic shift. Other less likely etiologies in the differential diagnosis of a narrow anterior chamber included plateau iris, idiosyncratic anterior rotation of the ciliary body, ciliary body effusion, or ciliary body mass.
Anterior segment ultrasound biomicroscopy (UBM) was obtained to evaluate the anterior chamber angle, anterior chamber depth and ciliary body using Paradigm (Paradigm Medical Industries, Salt Lake City, Utah) and iScience UBMs (iScience Surgical, Menlo Park, CA). UBM demonstrated a normal ciliary body (see Fig. 3) without anterior rotation or swelling of the ciliary body. UBM in the right eye, furthermore, demonstrated a forward iris contour with a more narrow anterior chamber angle and intermittent regions of angle closure (see Fig. 4). Iridolenticular touch consistent with pupillary block was visible using the UBM (see Fig. 5). In contrast, such findings were absent in the left eye. The central anterior chamber depth was also notably more shallow in the right than in the left eye by UBM, 1.7 and 3.0 mm, respectively (see Fig. 6).
Figure 3. 50 MHz UBM (paradigm) of the Ciliary Body in the Right Eye. No Swelling, Rotation, or Mass was Noted in the Ciliary Body.
Figure 4. 80 MHz UBM (iScience) Comparison of Central Anterior Chamber Angle Between the Right Eye (Left, Top and Bottom) and the Left Eye (Right, Top and Bottom). Note the Narrower Angle as Well as the Forward Bowed Iris Contour in the Angle Closure of the Right Eye (Left, Top and Bottom).
Figure 5. 50 MHz UBM (Paradigm) Demonstrates Iris Bombe with Iridolenticular Touch in the Right Eye.
Figure 6. 50 MHz UBM (Paradigm) Comparing the Central Anterior Chamber Depth in Right (top) vs the Left (bottom) Eye. Note the Significantly More Shallow Anterior Chamber in the Right Eye.
These slit lamp and ultrasound findings confirmed pupillary block as part of the mechanism for the narrow angle and excluded other causes such as plateau iris, effusion, or mass of the ciliary body. The underlying cause of the pupillary block was secondary to anterior subluxation of the lens associated with PXF zonular laxity. A phacomorphic component was doubtful because the lens diameters in both eyes were similar and normal. A laser peripheral iridotomy was recommended to the patient to alleviate the appositional angle closure in the right eye. A laser iridotomy was also recommended for the left eye given the presence of PXF material and risk of zonular laxity with anterior lens subluxation similar to that in the right eye.
After discussion of the risks, the benefits, alternatives, and indications for laser peripheral iridotomy were discussed. The patient wished to proceed and informed consent was obtained. A laser peripheral iridotomy was performed using a combination of pre-treatment with argon laser with subsequent Nd:YAG laser to complete the iridotomy. In post-laser treatment, the patient’s IOP was stable at 25 mm Hg in the right eye with the chamber visibly deeper immediately after the creation of a patent iridotomy (see Fig. 7). The patient was started on combination timolol/dorzolamide twice daily as well as prednisolone acetate four times daily for 1 week.
Figure 7. Slit Lamp Photograph of the Right Eye Before (top) and After Laser Iridotomy (bottom). Note the Loss of the Iris Bombe and the Significantly Deeper Chamber After the Laser Peripheral Iridotomy.
One week following laser treatment, the patient’s vision with his existing correction was 20/30 OD, 20/20 OS. The IOP was 15 mm Hg OU and the patient reported improvement in his vision as well as in his headaches. Gonioscopy was repeated in the right eye, and angle structures were now open to the scleral spur 360° without PAS. A prophylactic laser iridotomy was performed in the left eye without complication. The patient was started on prednisolone acetate four times daily in the left eye and asked to return to clinic in 1 week.
Two weeks after performing the laser iridotomy in the right eye, the visual acuity with correction was 20/25 OD, and 20/20 OS (as obtained with the refraction at the time of presentation) and his IOP was 16 and 14 mm Hg OS. The patient’s ocular medications included combination timolol/dorzolamide in the right eye and prednisolone acetate in the left eye. Both anterior chambers remained deep and quiet with patent superior laser peripheral iridotomies. At this visit, another UBM was obtained in both eyes followed by a dilated examination in both eyes. The UBM demonstrated stable findings in the left eye. The right eye, in contrast, demonstrated an absence of iris bombé configuration and much wider anterior chamber angle. The central chamber depth was significantly greater measuring 2.7 mm compared with 1.7 mm prior to laser peripheral iridotomy (Fig. 8). The anterior chamber depth in the right eye was now nearly equivalent to the left eye (3.0 mm). A Vossius ring was present to post-dilation in the right eye serving as a reminder of the previously existing pupil block secondary to pupillary iridolenticular adhesions.
Figure 8. 50 MHz UBM (Paradigm) Demonstrating the Anterior Chamber Depth Prior to (top) and After (bottom) Laser Peripheral Iridotomy in the Right Eye. Note the Significantly Increased Central Anterior Chamber Depth After the Laser Iridotomy.
PXF is among the leading causes of secondary open-angle glaucoma. However, PXF can also be associated with progressive angle narrowing and subsequent development of angle closure glaucoma. The incidence of narrow angles in PXF is higher than that in the average population. Clinically apparent PXF material observed by slit lamp or PXF material found on conjunctival biopsy was present in 28.3% of 60 patients with angle closure glaucoma or occludable angles3. The cumulative incidence of angle closure in PXF is estimated to be 2.2%.8
Gonioscopy of 76 patients with PXF, the majority with PXF glaucoma, demonstrated occludable angles in 18% of examined patients.7 In another study, the incidence of occludable angles was 23% in a group of 100 patients.5 Tarkkanen found the incidence of occludable angles to be 15% in patients with PXF glaucoma and 6% in individuals PXF without glaucoma.6 The results from these earlier studies, however, could have been affected by the presence of pharmacologic therapy with miotics. PXF patients who were not on any medical therapy had a 9.3% incidence of occludable angles.8
The etiology for this increased incidence of narrow and occludable angles has not been well characterized. With simple anatomic narrow angles, the underlying cause is a shorter axial length with a more crowded anterior chamber angle.1,11,12 Although biometry was not obtained, the average refractive error in PXF patients with occludable angles was observed to be +3.13 +/– 2.05 compared with +0.36 +/– 2.81 in patients with non-occludable angles.8 This suggests that PXF patients with occludable angles are more hyperopic. Although this group of PXF patients may, therefore, have an anatomic predisposition, this hypothesis was not confirmed by axial length measurements. Furthermore, the overall refractive error in the PXF population in this study was not hyperopic and the mechanism may therefore be independent of PXF. Bartholomew compared the anterior chamber depth between normals and PXF and found no difference.13 Forsius et al. similarly found no difference in anterior chamber depth in eyes with or without PXF.14 In contrast, Gharagozloo et al.15 found a smaller anterior chamber volume in eyes PXF vs controls. Larger studies evaluating axial lengths and refractive error in the PXF population remain to be performed.
Other etiologies hypothesized for causing angle closure in PXF are related to the increased tendency to form posterior synechiae, increased iris rigidity,16 and anterior lens displacement from zonular weakness associated with PXF. Another etiology not exclusive to PXF is a phacomorphic lens effect. The increased tendency for posterior synechiae formation in PXF eyes is believed to stem from PXF material that is present on both the posterior iris pigment epithelium and anterior lens capsule. This coating of both ocular surfaces with PXF material may make them “sticky” and subsequently adhere to each other and predispose to pupillary block. The tendency for synechiae to form in PXF eyes is further aggravated by treatment with miotics, as pupil excursion is decreased while lens-iris apposition is increased from forward rotation of the lens diaphragm.
Iris rigidity16 associated with PXF may also be a contributing factor for angle narrowing. Iris rigidity is believed to be induced by atrophy and fibrosis of the pupillary sphincter, ischemia, and loss of iris pigment epithelium combined with infiltration of iris tissues with PXF material. A more inflexible iris may result in a flat iris contour and poor dilation. Posterior pressure from aqueous humor outflow, therefore, exerts its effect mostly near the iris root thereby inducing a peripheral bowing of the iris, ie creating a pseudo-plateau configuration. This pseudo-plateau iris may be relieved with a peripheral iridotomy, unlike true plateau iris.
Finally, anterior lens displacement of the lens secondary to zonular weakness and dehiscence can increase the risk of pupillary block from increased iridolenticular contact. Lanzl et al. evaluated the anterior chamber depth in the supine and prone position in patients with clinically apparent unilateral PXF material.17 The lens was more mobile in the PXF involved eye as demonstrated by a decrease in anterior chamber depth in the prone vs supine position (although the difference was small). Esaki et al. also evaluated the anterior chamber depth in PXF eyes with postural change and similarly observed a decreased anterior chamber depth in the prone position.18 These findings are limited by the absence of a comparison with a normal population. Nonetheless, zonular weakness has been reported to be associated with PXF.1
Kuchle examined the anterior chamber depth and occurrence of complications during cataract extraction19,20 in PXF eyes. Complications such as zonular dialysis in those eyes with a shallow anterior chamber depth were significantly more frequent. An anterior chamber depth less than 2.5 mm had a 13.4% risk for complications vs 2.8% for an anterior chamber depth greater than 2.5 mm. The presence of a narrow anterior chamber in PXF eyes appears to suggest a higher than average risk of zonular weakness and therefore increased risk of zonular dehiscence during cataract surgery.
In summary, we present a case of acute angle closure secondary to pupillary block relieved by laser peripheral iridotomy. The pupillary block occurred secondary to progressive angle narrowing associated with PXF. Pupillary block was induced by progressive anterior lens movement arising from zonular weakness as a consequence of PXF, although a combination of mechanisms may have contributed including iris rigidity and morphologic lens changes. With UBM and slit lamp examination, iris bombe secondary to pupillary block was visualized and resolved following laser iridotomy. This case illustrates some of the mechanisms involved with inducing angle closure in PXF, which have not been well demonstrated in the literature. This case also importantly demonstrates the need to routinely examine the relative anterior chamber depth and angle in PXF eyes, especially between PXF eyes. Patients on miotics may have an increased risk of pupillary block, especially in the presence of PXF. These patients may benefit from prophylactic iridotomy in the contralateral PXF eye to prevent similar pupillary block glaucoma. Careful slit lamp examination may reduce complications in those patients who are to undergo cataract extraction with planning for possible complications secondary to PXF-associated zonular weakness and laxity. Future studies are needed to better understand the mechanisms underlying narrow angles in the setting of PXF and the pathogenesis of PXF glaucoma.
- Allingham RR, Damji K, Freedman S, Moroi S, Shafranov G. Pseudoexfoliation syndrome. In: Shields’ Textbook of Glaucoma. Philadelphia: Lippincott Williams & Wilkins, 2005;272–287.
- Lee RK. The molecular pathophysiology of pseudoexfoliation glaucoma. Curr Opin Ophthalmol. 2008;19:95–101. doi:10.1097/ICU.0b013e3282f49cda [CrossRef]
- Ritch R. Exfoliation syndrome and occludable angles. Trans Am Ophthalmol Soc. 1994;92:845–944.
- Lowe RF. Primary Angle-closure glaucoma with capsular exfoliation of the Lens. Br J Ophthalmol. 1964;48:492–494. doi:10.1136/bjo.48.9.492 [CrossRef]
- Layden WE, Shaffer RN. Exfoliation syndrome. Am J Ophthalmol. 1974;78(5):835–841.
- Tarkkanen A. Pseudoexfoliation of the lens capsule. A clinical study of 418 patients with special reference to glaucoma, cataract, and changes of the vitreous. Acta Ophthalmol Suppl. 1962;Suppl 71:1–98.
- Wishart PK, Spaeth GL, Poryzees EM. Anterior chamber angle in the exfoliation syndrome. Br J Ophthalmol. 1985;69:103–107. doi:10.1136/bjo.69.2.103 [CrossRef]
- Gross FJ, Tingey D, Epstein DL. Increased prevalence of occludable angles and angle-closure glaucoma in patients with pseudoexfoliation. Am J Ophthalmol. 1994;117:333–336.
- Herbst RW. Angle closure glaucoma in a patient with pseudoexfoliation of the lens capsule. Ann Ophthalmol. 1976;8:853–856.
- Gohdo T, Takahashi H, Iijima H, Tsukahara S. Ultrasound biomicroscopy of angle closure glaucoma with pseudoexfoliation syndrome. Br J Ophthalmol. 1997;81:706–707. doi:10.1136/bjo.81.8.705b [CrossRef]
- Lowe RF. Etiology of the anatomical basis for primary angle-closure glaucoma. Biometrical comparisons between normal eyes and eyes with primary angle-closure glaucoma. Br J Ophthalmol. 1970;54: 161–169. doi:10.1136/bjo.54.3.161 [CrossRef]
- Quigley H, Friedman DS, Congdon NG. Possible mechanisms of primary angle closure and malignant glaucoma. J Glaucoma. 2003;12:167–180. doi:10.1097/00061198-200304000-00013 [CrossRef]
- Bartholomew RS. Anterior chamber depth in eyes with pseudoexfoliation. Br J Ophthalmol. 1980; 64:322–323. doi:10.1136/bjo.64.5.322 [CrossRef]
- Forsius H, Sveinsson K, Als E, et al. Pseudoexfoliation of the lens capsule and depth of anterior chamber in northern Iceland. Acta Ophthalmol (Copenh). 1974;52:421–428. doi:10.1111/j.1755-3768.1974.tb01753.x [CrossRef]
- Gharagozloo NZ, Baker RH, Brubaker RF. Aqueous dynamics in exfoliation syndrome. Am J Ophthalmol1992;114:473–478.
- Ritch R. Exfoliation syndrome. In: Ritch R, Shields MB, Krupin T, eds. The Glaucomas. St. Louis: Mosby-Year Book; 1996:993–1022.
- Lanzl IM, Merté RL, Graham AD. Does head positioning influence anterior chamber depth in pseudoexfoliation syndrome?J Glaucoma. 2000;9:214–218.
- Esaki K, Ito K, Matsunaga K, et al. Anterior chamber structural change in postural variation in pseudoexfoliation syndrome. Nippon Ganka Gakkai Zasshi. 2001;105:524–529.
- Küchle M, Viestenz A, Martus P, et al. Anterior chamber depth and complications during cataract surgery in eyes with pseudoexfoliation syndrome. Am J Ophthalmol. 2000;129:281–285. doi:10.1016/S0002-9394(99)00365-7 [CrossRef]
- Desai MA, Lee RK. The medical and surgical management of pseudoexfoliation glaucoma. Int Ophthalmol Clin. 2008;48:95–113. doi:10.1097/IIO.0b013e318187e902 [CrossRef]