Hypotony maculopathy - Semantic Scholar

Acta Ophthalmologica Scandinavica 2007

Review Article

Hypotony maculopathy Vital Paulino Costa1,2 and Enyr Saran Arcieri1,3 1

Glaucoma Service, Department of Ophthalmology, University of Campinas, Saõ Paulo, Brazil 2 Department of Ophthalmology, University of Saõ Paulo, Saõ Paulo, Brazil 3 Department of Ophthalmology, School of Medicine, Federal University of Uberlaˆndia, Minas Gerais, Brazil

ABSTRACT. Hypotony maculopathy, first described in 1954 by Dellaporta, usually occurs after antiglaucomatous surgery or after perforating eye injuries; it is characterized by hypotony associated with fundus abnormalities, including papilloedema, vascular tortuosity and chorioretinal folds. In hypotony maculopathy, the scleral wall collapses inward, resulting in redundancy of the choroid and retina, leading to chorioretinal wrinkling. As the antero-posterior diameter of the vitreous cavity decreases, the very thick perivofeal retina surrounding the very thin foveal retina is thrown into radial folds around the fovea. It has been reported that hypotony maculopathy occurs in up to 20% of cases of glaucoma filtering surgery and has become more common after the introduction of antimetabolites. Young age, myopia, primary filtering surgery, systemic illnesses and elevated preoperative intraocular pressure (IOP) have been found to be associated with hypotony maculopathy. Hypotony maculopathy is treated with procedures designed to elevate IOP, which may reverse the inward scleral bowing and improve visual acuity. The successful treatment of hypotony maculopathy depends on the correct identification of its cause. Once the cause is detected, treatment should be employed as soon as possible because delayed normalization of the IOP may result in permanent macular chorioretinal changes and poor vision. This review will explore the definition, mechanisms, clinical findings and treatment of hypotony maculopathy. Key words: hypotony maculopathy – clinical findings – mechanisms – tonometry – ocular – ciliary body – glaucoma – trabeculectomy

Acta Ophthalmol. Scand. 2007: 85: 586–597 ª 2007 The Authors Journal compilation ª 2007 Acta Ophthalmol Scand

doi: 10.1111/j.1600-0420.2007.00910.x

Definition, history and synonyms There are two definitions of hypotony. ‘Statistical’ hypotony can be defined as an intraocular pressure (IOP) less than 6.5 mmHg, which corresponds to more than three standard deviations below the mean;

586

‘clinically significant’ hypotony represents the condition where the IOP is low enough to result in visual loss (Pederson 1996). There are several causes of visual loss secondary to low IOPs, including hypotony maculopathy, keratopathy, cataract formation, choroidal effusion, optic nerve oedema, irregular astigmatism and

even phthisis bulbi (Fannin et al. 2003). This review will explore the definition, mechanisms, clinical findings and treatment of hypotony maculopathy. Hypotony maculopathy was first described by Dellaporta (1954). In this publication, he assembled four cases that had been reported between 1946 and 1954 (Renard 1946; Dellaporta 1948; Pau 1950). He recognized that the condition occurred usually after antiglaucomatous surgery or after perforating eye injuries, and stressed that ‘the striking common characteristic of the four reported eyes was ocular hypotony of about 8–10 mmHg’. The syndrome was characterized by hypotony associated with fundus abnormalities, which included papilloedema, vascular tortuosity and chorioretinal folds. Since the papilloedema was usually of moderate degree and was not associated with retinal haemorrhages, the term ‘papilloedema ex vacuo’ was proposed in order to clearly distinguish this condition from the true papilloedema because of increased intracranial pressure (Dellaporta 1954). Several years later, Gass (1972) coined the term ‘hypotony maculopathy’, chosen only to emphasize that alterations in the macular region were primarily responsible for the loss of central vision. Although ‘hypotony chorioretinopathy’ might be a more accurate term to describe the fundoscopic changes, which may involve virtually the entire ocular fundus, we decided to maintain the term ‘hypotony maculopathy’ throughout this


article because it is more commonly used in the medical literature.

Clinical findings Hypotony maculopathy corresponds to a condition where hypotony leads to papilloedema associated with wrinkling or folding of the retina and choroid throughout the posterior pole. In the macular area, there are several

fine retinal folds radiating outward from the fovea (Fig. 1). The folding results in distortion of the neurosensorial elements of the retina and reduction of the antero-posterior diameter of the eye, leading to a relative hyperopia. The chorioretinal folds are particularly evident in the macula. In this area, the very thick perifoveal retina surrounding the very thin foveal retina is thrown into radial folds around the fovea (Gass 1972).

Fig. 1. Clinical photograph of an eye with hypotony maculopathy showing disc swelling and several fine retinal folds radiating outward from the fovea at the macular area. The retinal vessels appear tortuous and the retinal veins are engorged.

Fig. 2. Clinical photograph of hypotony maculopathy showing retinal folds and alternate light and dark streaks in the fundus.

With the onset of hypotony, the posterior scleral wall probably begins to shrink or collapse, throwing the choroid and retina into folds. As the wrinkling or folding becomes more prominent, the relative compression of pigment epithelial cells in the trough of the fold and the relative thinning of the pigment epithelium over the crest produce the alternate dark and light coloured streaks that can be observed ophthalmoscopically (Fig. 2). In prolonged hypotony, the intensification of the alternate light and dark streaks in the fundus is probably caused by alterations in the structure and pigment content of the retinal pigment epithelial cells (Figs 2 and 3). Acutely acquired chorioretinal folds usually produce visual dysfunction caused by distortion of the overlying retinal receptors. In hypotony maculopathy, the distortion of the photoreceptors is probably associated with other hypotony-induced changes (such as irregular astigmatism) that exacerbate the visual disturbance caused by the chorioretinal folds. These folds may have a horizontal, oblique or vertical orientation, although an irregular or radiating pattern may be present. The longer the duration of the folds, the more prominent they appear. Cystoid macular oedema caused by abnormal retinal capillary permeability may ensue secondary to a reduction in the interstitial pressure (Kokame et al. 2001; Stefansson 2006). However, this is not a common finding, and – even if present – is of secondary importance as a cause of visual loss in these eyes. The retinal vessels appear tortuous, and the retinal veins engorged (Figs 1 and 3). Serous detachment of the peripheral choroid is usually absent at indirect ophthalmoscopy (Gass 1972), but may be recognized with ultrasound biomicroscopy (Coleman 1995). Papilloedema is probably the result of anterior bowing of the lamina cribrosa, constricting axonal bundles in the lamina scleralis and reducing orthograde and retrograde axoplasmic transport (Minckler & Bunt 1977) (Figs 1 and 3). Disc swelling is less frequent in patients with advanced optic nerve damage, because there are fewer axons left to suffer changes in axoplasmic flow.

587


Fig. 3. Clinical photograph of an eye with hypotony maculopathy showing marked disc swelling.

Imaging Fluorescein angiography is helpful in demonstrating the chorioretinal folds, which in relatively mild degrees may be overlooked (Fig. 4). It is also useful in differentiating folds of the choroid and retinal pigment epithelium (RPE) from folds in the retina, which do not alter background fluorescence. Early in the course of hypotony, fluorescein angiography shows an irregular increase in background choroidal fluorescence corresponding to the crest of the choroidal folds and also shows some evidence of leakage of dye from the capillaries on the optic nerve head, but usually not from the retinal capillaries

(A)

(Gass 1972). Characteristic changes in the background choroidal fluorescence are caused by folding of the choroid and RPE. Intensification of the choroidal fluorescence occurs along the crest of the choroid and RPE and produces a series of relatively hyperfluorescent streaks that are evident as early as the arterial phase. The hyperfluorescent streaks are caused by the relative thinness of the RPE on the crest, the greater thickness of the pool of choroidal dye beneath the crest and the shorter course of the incident blue and reflected yellow-green light through the RPE on the crest. The troughs of the folds appear relatively hypofluorescent. This results in angiographic

finding of narrow dark lines running within a background of normal or slightly intensified background choroidal fluorescence. Indocyanine green angiography may reveal multiple hypofluorescent spots in many parts of the fundus, sector hypofluorescent areas, dilatation and tortuosity of the choroidal vessels in the posterior pole of hypotonous eyes, even if fluorescein angiography is not able to detect them (Masaoka et al. 2000). B-scan ultrasonography is especially useful when the fundus is not easily visualized. It can help in excluding the presence of ciliochoroidal detachment, suprachoroidal haemorrhage and retinal detachment, which are not commonly seen in cases of hypotony maculopathy. Ultrasonography usually demonstrates some flattening and thickening of the posterior sclera and choroid, but identifying the chorioretinal folds may be difficult (Cappaert et al. 1977) (Fig. 5). Ultrasonic biomicroscopy can be employed (Fig. 6) to further evaluate the anterior chamber depth, the position of the ciliary body and the presence of anterior ciliary detachment (Roters et al. 2002). Furthermore, it can be used to identify a cyclodialysis cleft, one of the important causes of hypotony maculopathy (Bhende et al. 1999; Chan et al. 2000). Intraoperatively, the ciliary body can be directly visualized to evaluate rotation and traction using endoscopy (Hammer & Grizzard 2003; Gnanaraj et al. 2005). Optical coherence tomography (OCT) of the posterior pole can help to better demonstrate subtle macular fluid or folds. OCT can be helpful in

(B)

Fig. 4. Picture and fluorescein angiography of a patient with hypotony maculopathy. Fluorescein angiography (B) is helpful in demonstrating the chorioretinal folds, which in relatively mild degrees may be overlooked (A). (Reprinted from Handbook of Glaucoma, Azvara-Blanco A, Costa VP, Wilson RP (eds.), 2002, London: Martin Dunitz.)

588


man with a long history of glaucoma, who underwent trabeculectomy in the right eye. Magnetic resonance imaging showed an abnormal plaque-like thickening of the macula and flattening of the posterior globe.

Aetiology, histopathology and mechanisms

Fig. 5. B-scan ultrasonography of an eye with hypotony maculopathy showing thickening of the choroid (between arrows).

Fig. 6. Ultrasound biomicroscopy revealing fluid in the supraciliary space (arrow) with no cyclodialysis cleft in a patient with hypotony maculopathy.

diagnosing suspected hypotony maculopathy in patients with reduced visual acuity (VA) and normal ocular examination, except for low IOPs. Budenz et al. (2005) suggested that because retinal folds are typically oriented in the 0–180 axis, careful review of all radial line scans may be necessary to diagnose this condition (Fig. 7). Martinez de la Casa et al. (2003) reported the case of a 40-year-old man who underwent trabeculectomy and showed hypotony and VA loss.

Although no alterations were noted on opthalmoscopy or on fluorescein angiography, OCT allowed the diagnosis of hypotony maculopathy. Kokame et al. (2001) described a case where OCT allowed the detection of not only choroidal folds but also intraretinal cysts and serous retinal detachment associated with hypotony maculopathy. Westfall et al. (2004) reported the magnetic resonance appearance of hypotony maculopathy in a 48-year-old

Any condition leading to reduced IOP may result in hypotony maculopathy. Causes of hypotony are listed in Table 1, although the discussion of these extends beyond the scope of this article. Hypotony occurs when aqueous humour production does not keep pace with outflow. Outflow may be greater than usual, as seen with a wound leak, an overfiltering bleb or a cyclodialysis cleft. Conditions that alter ciliary body function, such as iridocyclitis, ciliochoroidal detachment or hypoperfusion, may cause inadequate aqueous humour production (Newhouse & Beyrer 1982; Toris & Pederson 1987; Pederson 1996; Kato et al. 1999; Fannin et al. 2003). Although hypotony maculopathy is usually seen after glaucoma filtering surgery, especially with adjunctive mitomycin C (MMC), it can also be observed following other ocular conditions (Hatton et al. 1998; Foster et al. 1999; Deramo et al. 2001; Ichibe et al. 2002). Inflammation may play a key role in the evolution of hypotony. It causes increased permeability of the blood– aqueous barrier. Choroidal fluid is believed to accumulate as a result of enhanced uveoscleral outflow and decreased aqueous humour production, a cycle that is often perpetuated once choroidal effusion develops. A ring of anterior choroidal fluid can rotate the ciliary body forward, impairing its ability to produce aqueous humour (Weekers & Delmarcelle 1953; de Smet et al. 2005). Dellaporta (1954) believed that, in hypotonic eyes, the protruding nerve head pulled the nerve-fibre layer causing friction between the retina and the pigment epithelium of the retina along the nerve fibres. This friction would cause irritation and subsequent gradual increased pigmentation. He also believed that the tendency for the choroidal folds to have a linear branching course radiating in a temporal

589


Fig. 7. Optical coherence tomography with macular scan using Stratus OCT (Zeiss Meditec, Dublin, California, USA) showing folding of the retinal and choriocapillaris layers because of hypotony maculopathy. (Reprinted from Archives of Ophthalmology 2005, 123: 113–114. Copyright ª 2005, American Medical Association. All rights reserved.)

direction away from the optic disc, and to have a cobblestone, flagstone, hexagonal or quilt-like pattern nasally, was probably caused by several factors including structural differences between the choroid and sclera and unequal forces exerted in the collapse of the ocular coats during eye movement by virtue of the oblique and nasal insertion of the optic nerve head. Gass (1972) proposed the theory that is now accepted to explain the mechanism of hypotony maculopathy. He suggested that hypotony could cause the scleral wall to collapse inward, resulting in redundancy of the choroid and retina, which would lead to chorioretinal wrinkling. The unusual configuration of retinal folding is a result of the peculiar anatomy of

the retina in the macula. As the antero-posterior diameter of the vitreous cavity decreases in hypotony, the very thick perivofeal retina surrounding the very thin foveal retina is thrown into radial folds around the fovea (Gass 1972) (Fig. 8). Several authors have subsequently confirmed that any condition causing a reduction in the area of the inner surface of the sclera (scleral thickening or scleral shrinkage) may cause the inner portion of the choroids, the overlying retinal pigment epithelium and the outer retinal layers to be thrown into a series of folds or wrinkles (Dellaporta 1950; Norton 1969; Hyvarinen & Walsh 1970; Kroll & Norton 1970; François & DeLaey 1971; Von Winning 1972; Newell 1973; Cangemi et al. 1978; Kalina &

Mills 1980; Morris & Sanders 1980; Lebuisson et al. 1981; Gass 1987). The origin of papilloedema was explained in a series of experimental studies. According to Minckler & Bunt (1977), hypotony could lead to anterior bowing of the lamina cribrosa, constricting axonal bundles in the lamina scleralis and reducing orthograde and retrograde axoplasmic transport. In a subsequent study, Floyd & Minckler (1983) demonstrated that leakage from the choriocapillaris could be an additional source of the fluid that accumulates in the disc. They speculated that swollen axons, caused by blockage of the axoplasmic transport, could compromise the blood flow to the optic nerve, resulting in hypoxia, endothelial cell damage and leakage. Histopathologic findings in eyes with hypotony have been described by Collins (1917), who demonstrated thickening and folding of the sclera and folding of Bruch’s membrane, associated with accumulation of retinal pigment epithelium in the depths of the choroidal folds. Histopathology of hypotonic eyes may also demonstrate generalized oedema of the uvea, retina and optic nerve, as well as a proteinaceous fluid in the suprachoroidal space (Volcker & Naumann 1979).

Incidence and risk factors The initial literature on hypotony maculopathy included several reports of cases; these did not allow the evaluation of its incidence. More recently, hypotony maculopathy has been reported to occur in up to 20% of cases of glaucoma filtering surgery (Whiteside-Michel et al. 1992; Costa et al. 1993c; Kitazawa et al. 1993;

Table 1. Causes of hypotony. Postoperative hypotony

Hypotony after trauma

Wound leak Iridocyclitis Overfiltration Retinal detachment Iridocyclitis Cyclodialysis Ciliochoroidal detachment Scleral rupture Retinal detachment Ciliochoroidal detachment Cyclodialysis Scleral perforation MMC-induced toxicity of the ciliary body MMC, mitomycin C.

590

Bilateral hypotony

Miscellaneous forms of hypotony

Osmotic Dehydration Diabetic coma Uremia Myotonic dystrophy

Vascular occlusive disease (ciliary body hypoperfusion) Carotid occlusion Temporal arteritis Central retinal artery or vein occlusion PVR or cyclitic membrane pulling the ciliary body Prephthisis bulbi


Fig. 8. Normal eye (A, B). Mild hypotony with thickening of the choroid, initial scleral shrinking and disc oedema (C, D). Severe hypotony maculopathy with choroidal and retinal folds, macular striae, disc oedema, dilated retinal veins and scleral shrinking (E, F).

Shields et al. 1993; Me´gevand et al. 1995; Bell et al. 1997; Cheung et al. 1997; Zacharia & Schuman 1997; Perkins et al. 1998; Rasheed 1999; Lanzl et al. 2000; Martinez Garcia & Perez Garcia 2000; Mietz & Krieglstein 2001; Bindlish et al. 2002; Mietz et al. 2002; Tsai et al. 2003) (Table 2). Although the description of hypotony maculopathy dates from 1955 (Dellaporta 1954), reports of this complication became frequent only after the introduction of antimetabolites in glaucoma surgery. In a review of 40 eyes with hypotony (IOP < 10 mmHg) post-trabeculectomy without antimetabolites followed for 3.4 years, Cristiansson (1967) reported persistent degenerative macular changes in four eyes, but there was

no mention of the presence of chorioretinal folds or the effect of this finding on VA. Costa et al. (1993b) reviewed the charts of 440 patients (508 eyes) who underwent trabeculectomy to detect cases of postoperative VA loss (two or more Snellen lines or a category change). In this series, six eyes (1.2%) showed loss of VA because of hypotony maculopathy. Among the six eyes, three (50%) had received postoperative applications of 5-fluouracil (5-FU) injections. Hypotony maculopathy was associated with coronary artery disease (P ¼ 0.0397) and systemic hypertension (P ¼ 0.0118). Whiteside-Michel et al. (1992) evaluated the effectiveness of initial trabeculectomy with adjunctive 5-FU for

uncomplicated glaucoma in 20 eyes of 20 patients younger than 40 years old. Subconjunctival injections of 5-FU (5 mg) were given 180 from the operative site within 14 days of surgery. Hypotony maculopathy was observed in one patient (5%). Mitomycin C appears to be even more likely to produce hypotony, with the occurrence ranging from 3% to 20% in various series (Costa et al. 1993c; Kitazawa et al. 1993; Shields et al. 1993; Me´gevand et al. 1995; Cheung et al. 1997; Zacharia & Schuman 1997; Perkins et al. 1998; Rasheed 1999; Lanzl et al. 2000; Martinez Garcia & Perez Garcia 2000; Mietz & Krieglstein 2001; Bindlish et al. 2002; Mietz et al. 2002; Tsai et al. 2003). In a prospective, randomized study, Rasheed (1999) compared the overall efficacy of intraoperative application of MMC in eyes with no previous ocular surgery to standard trabeculectomy without MMC. Twenty-five patients with primary glaucoma were treated with trabeculectomy without antimetabolites in one eye and trabeculectomy with MMC in the contralateral eye. After a mean follow-up of 18 months, hypotony maculopathy developed in three eyes (12%) of the MMC group, and was not observed in the group that did not receive antimetabolites. Other studies have suggested that high concentrations of MMC or increased exposure time to MMC may be associated with the development of hypotony maculopathy (WhitesideMichel et al. 1992; Kitazawa et al. 1993; Oppenheim & Ortiz 1993; Shields et al. 1993; Zacharia et al. 1993; Neelakantan et al. 1994; Me´gevand et al. 1995). Zacharia et al. (1993) reported an incidence of 32.7% of hypotony (IOP < 5 mmHg) in 52 eyes of 48 patients undergoing trabeculectomy with MMC (0.4 mg ⁄ mL for 3.7–7 min). Twenty-two eyes requiring bilateral primary trabeculectomy were randomized by Kitazawa et al. (1993) to intraoperative MMC (0.2 mg ⁄ mL for 5 min) in one eye and to low-dose intraoperative MMC (0.02 mg ⁄ mL for 5 min) in the contralateral eye. Two cases (18.2%) of transient hypotony maculopathy were noted in the 0.2 mg ⁄ mL group exclusively. Me´gevand et al. (1995) compared the results of 25 eyes that were considered to be at high risk for surgical failure

591


Table 2. Incidence of hypotony maculopathy following trabeculectomy or combined (phacoemulsification + trabeculectomy) procedures in different studies. Author Whiteside-Michel et al. (1992) Costa et al. (1993a) Shields et al. (1993)

Kitazawa et al. (1993) Me´gevand et al. (1995) Cheung et al. (1997) Zacharia & Schuman (1997) Bell et al. (1997) Perkins et al. (1998) Rasheed (1999) Lanzl et al. (2000) Martinez Garcia & Perez Garcia (2000) Mietz & Krieglstein (2001)

Mietz et al. (2002) Bindlish et al. (2002) Tsai et al. (2003)

Type of surgery

Antimetabolites (dose)

Follow-up (months)

Incidence (%)

20 39 15 59

TREC TREC PHACOTREC TREC

31.1 ± 17.3 (11.5–70) 6.7 ± 0.7 6.8 ± 0.9 2 to 12 (mean 5.0–6.3)

11 11 25 48 157 20 45 68 25 25 10 34

TREC TREC TREC TREC TREC PHACOTREC TREC TREC TREC TREC TREC TREC

5-FU (15–45 mg; mean 27.8 ± 8.8 mg) MMC (0.4 mg ⁄ mL; 1.5–2.5 min) MMC (0.4 mg ⁄ mL; 3.5 min) MMC (0.4 mg ⁄ mL) 2 min (n ¼ 17) ⁄ 3 min (n ¼ 17) ⁄ 4 min (n ¼ 8) ⁄ 5 min (n ¼ 10) MMC (0.02 mg ⁄ mL; 5 min) MMC (0.2 mg ⁄ mL; 5 min) MMC (0.2 mg ⁄ mL; 2 min) MMC (0.2 mg ⁄ mL; 5 min) MMC (0.2–0.5 mg ⁄ mL; 0.5–5 min) MMC (0.4 mg ⁄ mL; 1.0–3.5 min) 5-FU (25 mg ⁄ mL; 5 min) MMC (0.5 mg ⁄ mL; 0.5–5.0 min) No antimetabolite MMC (0.3–0.4 mg ⁄ mL; 4 min) MMC (0.4 mg ⁄ mL; 1.0–4.0 min) MMC (dose not available)

5% 7.7% 0 11.7% (2 min) 11.7% (3 min) 20% (5 min) 0 18.2% 0 2.1% 3.2% 5% 4.4% 5.9% 0 12% 10% 8.8%

10 10 20 24 24 123

TREC TREC TREC TREC TREC TREC

15 29

TREC TREC

n

Suramin (200 mg ⁄ mL; 5 min) MMC (0.2 mg ⁄ mL; 3 min) No antimetabolite Postoperative MMC (0.05 mg ⁄ mL)* MMC (0.2 mg ⁄ mL; 3 min) MMC (0.25 ⁄ 0.33 ⁄ 0.5 mg ⁄ mL; 0.5–5.0 min) MMC (0.2 mg ⁄ mL; 2 min) No antimetabolite

11.0 10.7 12.0 20.2 19.7 14.4 24.0 36.0 17.8 17.8 14.9 28.1

± 3.4 ± 3.2 (4–19) (4–35) ± 9.0 ± 3.1 (9.2–19.3) ± 6.9 (12–42) (93%) ± 1.2 ± 1.1 (9–19)

18.0 18.0 18.0 18.2 ± 6.5 19.0 ± 5.0 At least 60

0 10% 0 0 4.2% 8.9%

25.7 ± 21.4 27.7 ± 12.2

20% 0

TREC, trabeculectomy; PHACOTREC, phacotrabeculectomy; MMC, mitomycin C; 5-FU, 5-fluouracil. * Mitomycin-C (0.05 mg ⁄ mL) was applied topically to the filtering bleb on days 1, 2 and 3 after surgery (postoperative application).

and that received a single intraoperative application of MMC (0.2 mg ⁄ mL for 2 min) to a group of 48 patients – matched for age, race, type of refractory glaucoma and preoperative IOP – who received a single intraoperative application of MMC (0.2 mg ⁄ mL for 5 min). Hypotonyrelated maculopathy developed in one eye (2.1%) in the 5 min group. Costa et al. (1993a) reviewed the charts of patients who underwent primary trabeculectomies (group 1, n ¼ 39) or combined procedures (phacoemulsification + trabeculectomy ) group 2, n ¼ 15) and received intraoperative MMC (0.4 mg ⁄ mL ) 1.5– 3.5 min), and observed that hypotony maculopathy developed in three cases of group 1 (7.7%). Bindlish et al. (2002) investigated the 5 year incidence of hypotony maculopathy after trabeculectomy with MMC at various concentrations. Hypotony (IOP < 6 mmHg) occurred in 42.2% of eyes after a mean followup of 26.1 months, whereas hypotony maculopathy occurred in 8.9% of eyes at mean follow-up of 33.7 months.

592

The association between hypotony maculopathy and the use of antimetabolites is not exclusively because of the antifibrotic effect, leading to reduced scar formation and a tendency for overfiltration. It has been suggested that MMC may have a direct toxic effect on the ciliary body, resulting in reduced aqueous humour production (Nuyts et al. 1994a). Additionally, the application of antifibrotic agents in filtering surgery, such as MMC or 5-FU, may induce changes in the conjunctiva. The tissue frequently becomes avascular, which prevents migration of cells via the vascular route to induce fibrosis (Shields et al. 1993; Hutchinson et al. 1994; Sihota et al. 2000). Furthermore, Sihota et al. (2000) suggested that a dysfunctional conjunctival barrier, as evidenced by the ‘sweating’ of the bleb and histopathologic alterations in the epithelial barrier, could be coresponsible for the hypotonic maculopathy in eyes undergoing trabeculectomy with MMC. Certainly, the level of IOP alone does not determine who will develop

wrinkling of the choroid and retina. Factors such as scleral thickness, scleral rigidity, structural variations in the choroid and its vessels, extraocular muscle tone and duration of hypotony are probably important in the pathogenesis of hypotony maculopathy (Gass 1972). It is also important to notice the influence of central corneal thickness (CCT) on the diagnosis of hypotony maculopathy. Eyes with thin corneas may not develop hypotony maculopathy despite low IOPs, artificially reduced by the CCT value. On the other hand, eyes with thick corneas and IOPs of 8–9 mmHg may exhibit hypotony maculopathy despite apparently normal IOPs. Early on, Dellaporta (1954) noticed that ocular hypotony preceded by ocular hypertension and the relatively young age of the patients involved were important prerequisites to the development of hypotony maculopathy. The medical records of 186 patients with ocular hypotony following glaucoma surgery were reviewed by Fannin et al. (2003) in a


retrospective case series to determine risk factors for hypotony maculopathy. The mean age for eyes with maculopathy was 50.5 years versus 70.7 years for those eyes without maculopathy. Maculopathy was more frequent in myopic eyes and in eyes undergoing primary surgery. Furthermore, eyes with hypotony maculopathy had a lower frequency of choroidal effusion than non-maculopathy controls. Several authors confirmed that younger age, myopia, male gender and primary filtering surgery are risk factors for the development of hypotony maculopathy (Jampel et al. 1992; Stamper et al. 1992; Sun˜er et al. 1997; Palmberg 1998). The first two factors support the theory of low scleral rigidity as an important element in the pathogenesis of hypotony maculopathy (Gass 1972; Stamper et al. 1992). It is possible that low scleral rigidity facilitates the inward collapse of the scleral wall during hypotony, causing the chorioretinal wrinkling. The sclera of young patients is thought to be more elastic and flexible than that of older patients, and may shrink more in hypotonic conditions. Similarly, the sclera in patients with myopia tends to be thinner, less rigid and, thus, more likely to contract in hypotony (Gass 1972).

Differential diagnosis Chorioretinal folds may also develop in the absence of hypotony. The following situations may be associated with chorioretinal folds: (1) Idiopathic chorioretinal folds. Incidental finding in patients who are seen because of presbyopia and those who have normal or near-to-normal VA. These patients typically have hyperopia (1–6 dioptres or more). When the folds occur in the macular region, they are often roughly horizontal in their course or may radiate outward from the optic disc (Gass 1987). (2) Retrobulbar mass lesions. Orbital tumours as well as orbital implants, in some cases, may cause scleral oedema, choroidal congestion and chorioretinal folds (Kroll & Norton 1970; Wolter 1974; Friberg & Grove 1983). If the retrobulbar mass is removed or otherwise treated successfully, the

chorioretinal folds usually disappear (Kroll & Norton 1970). (3) Scleral inflammation. Thickening and inflammation of the sclera in thyroid eye disease, inflammatory pseudotumour of the orbit and rheumatoid scleritis may cause chorioretinal folds (Coleman 1995). (4) Scleral buckle. Thickening of the sclera in the vicinity of a scleral buckle for a rhegmatogenous retinal detachment may occasionally produce chorioretinal folds (Coleman 1995). (5) Choroidal tumours. Choroidal tumours, particularly malignant melanomas and metastatic carcinomas, may produce folds in the choroid and retina. These folds are produced by mechanical displacement of the surrounding choroid by the expanding tumour (Norton 1969). (6) Choroidal neovascularization. Contraction of a choroidal neovascular membrane (CNVM) and the underlying Bruch’s membrane occurring either spontaneously or after photocoagulation may cause a radiating pattern of chorioretinal folds around the membrane (Gass 1981).

Prevention and treatment The advent of antimetabolite therapy in glaucoma filtration surgery has resulted in an increased incidence of postoperative hypotony secondary to overfiltration. Modifications of the surgical technique, such as tighter scleral flap suturing and postoperative gradual increase in outflow with laser suture lysis or releasable sutures, should be used in order to avoid overfiltration and the occurrence of hypotony maculopathy (Savage et al. 1988; Melamed et al. 1990). Hypotony maculopathy is usually treated with procedures designed to elevate the IOP. Normalization of IOP may then reverse the inward scleral bowing. However, despite successful IOP elevation, VA may not return to normal, and permanent macular chorioretinal changes may ensue (Duker & Schuman 1994). The successful treatment of hypotony maculopathy depends on the correct identification of its cause. Once the cause is detected, treatment should be employed as soon as possible: delayed normalization of the IOP

may result in permanent macular chorioretinal changes and poor vision (Costa et al. 1993c; Nuyts et al. 1994b). Leakage of aqueous humour from a filtration bleb after glaucoma surgery may cause hypotony maculopathy. Conservative management, including the use of aqueous suppressants, pressure patching, collagen shield application or contact lens ⁄ shell ⁄ ring tamponade, may help to seal the leak (Ruderman & Allen 1985; Melamed et al. 1986; Fourman & Wiley 1989; Blok et al. 1990; Hill et al. 1990). One possible approach consists of aqueous suppressants, use of a contact lens and topical gentamicin therapy. Aqueous suppressants decrease production of aqueous humour and reduce bulk flow through the leak, thereby allowing epithelial proliferation; bandage contact lens facilitates epithelial migration; and topical aminoglycoside (e.g. gentamicin) incites mild conjunctival inflammation and stimulates wound healing (Tomlinson et al. 1987). There have also been successful reports of bleb leaks treated with lowpower argon laser application (Baum & Weiss 1993) or fibrin glue topical application (Kajiwara 1990). More recently, intrableb or subconjunctival peribleb injection of autologous blood has been described as a simple inoffice technique for treating chronic postfiltration hypotony (Wise 1993; Smith et al. 1995) (Fig. 9). Conjunctival compression sutures have also been used to induce adherence of conjunctiva to underlying tissues (Palmberg & Zacchei 1996; Palmberg 1996). Palmberg (1996) suggested that 9–0 nylon sutures could be employed to isolate the area of leakage, reducing the access of aqueous to the leakage site, or to limit the size of an overhanging bleb in cases of overfiltration (Fig. 10). The sutures applied to sectors of the conjunctiva in which the fibroblasts are viable may help induce sufficient healing response. However, this technique only affects the area of conjunctiva that is compressed, and, in our hands, this has been insufficient in cases where hypotony is caused by overfiltration and no leakage. When these sutures are used in association with subconjunctival injections of autologous blood, they may provide more effective management of hypotony

593


Fig. 9. Intrableb injection of autologous blood.

Fig. 10. Conjunctival compression sutures (under circle) employed to isolate the area of leakage of aqueous humour from a filtration bleb.

maculopathy following filtration surgery with mitomycin C (Haynes & Alward 1999). Finally, bleb excision with surgical revision, donor scleral graft patching and reconstruction of the filtering bleb with a free conjunctival autograft represent more invasive treatment modalities (Melamed et al. 1991; O’Connor et al. 1992; Buxton et al. 1994; Wilson & Kotas-Neumann 1994). These techniques are highly successful in increasing IOP by closing conjunctival leakage or decreasing filtration in overfunctioning blebs, with success rates varying from 80% to

594

94% (Budenz et al. 1999; Catoira et al. 2000; Burnstein et al. 2002; Bashford et al. 2004; Tannenbaum et al. 2004). However, a large proportion (up to 50%) of eyes undergoing surgery require antiglaucoma medications to control IOP, and some (up to 8%) may need new filtering procedures to reduce IOP (Budenz et al. 1999; Catoira et al. 2000; Burnstein et al. 2002; Bashford et al. 2004; Tannenbaum et al. 2004). Burnstein et al. (2002) compared the outcomes of conjunctival advancement and non-incisional management of late-onset glaucoma filtering bleb

leak in a retrospective, non-randomized trial. Fifty-one eyes of 48 patients who underwent management of late-onset glaucoma filtering bleb leaks were included. Thirty-seven eyes were included in the non-incisional treatment group and 34 eyes were included in the surgical revision group (conjunctival advancement with preservation of the preexisting bleb). The Kaplan-Meier cumulative probability of success at 24 months were 42% and 80%, respectively, for the nonincisional and surgical revision groups (P ¼ 0.0001, log-rank test). In eyes with hypotony maculopathy secondary to an overfiltering bleb, measures to incite inflammation at the bleb site are recommended to promote scarring and consequent reduction of aqueous flow. Multiple methods have been used in attempting to induce sufficient healing or fibrosis of the bleb to reverse the hypotony. It is recognized that cataract extraction performed in previously filtered eyes can cause inflammatory compromise of the filter, leading to postoperative increases in IOP (Oyakawa & Maumenee 1982; Shields 1982; Dickens & Cashwell 1996; Sibayan et al. 1997). Inflammation and scarring at the filtering site may also be stimulated by yttrium aluminium garnet (YAG) laser (Bettin et al. 1999), cryotherapy (Jampel et al. 1992; Stamper et al. 1992; Costa et al. 1993c; Nuyts et al. 1994b), diathermy (Stamper et al. 1992) and trichloroacetic acid application (Stamper et al. 1992; Nuyts et al. 1994b). Injection of autologous blood into the bleb has been described but is not without risk. It was first employed by Wise (1993), who successfully treated four eyes with chronic hypotony following MMC trabeculectomy. Nuyts et al. (1994b) reported that 17 (77.3%) of the 22 eyes that underwent intrableb autologous blood injection showed IOPs of 6 mmHg or greater after a mean follow-up of 20.7 weeks. Leen et al. (1995) investigated the efficacy of intrableb autologous blood injection in 12 eyes with overfiltering or leaking blebs, and observed a 58.3% success rate after an average follow-up of 6.8 months. Smith et al. (1995) demonstrated a 66.6% success rate following peribleb autologous blood injection into surrounding subconjunctival tissue after a minimum follow-up of 4 months. Ellong et al.


(2001) evaluated the effectiveness of intrableb autologous blood injections in 12 eyes with hypotony associated with overfiltration. After a mean follow-up of 12.3 months, the average IOP increased from 2.7 ± 1.2 mmHg to 8.2 ± 4.2 mmHg (P < 0.05). Yieh et al. (2001) described the use of autologous fibrinogen concentrate (AFC) to treat seven eyes with persistent post-trabeculectomy hypotony. Under a microscope, 0.2 mL AFC and bovine thrombin was injected into the blebs. On the second day, the mean IOP of seven eyes elevated from 3.4 ± 2.1 mmHg to 12.6 ± 4.2 mmHg; within 2 weeks, VA was noted to improve in six eyes (85.7%). Sometimes, the above-mentioned measures used to treat hypotony secondary to overfiltration do not reverse the problem because failure of scleral healing is the underlying cause. In these cases, resuturing the scleral flap or placing a scleral patch over the original flap is effective in reversing hypotony and restoring VA, while still maintaining some degree of filtration (Cohen et al. 1995; Schwartz et al. 1996; Halkiadakis et al. 2005; Harizman et al. 2005). Schwartz et al. (1996) reported four eyes that underwent trabeculectomy using topical mitomycin C and developed hypotony maculopathy unresponsive to non-surgical therapies. After a minimum follow-up of 18 months, the surgical revision with scleral flap closure increased the IOP, reversing the hypotony, and resulted in improved VA to 20 ⁄ 25 or better in all cases. Harizman et al. (2005) reported a modified technique of bleb revision with the use of a donor scleral patch in 15 eyes in which scleral melting did not allow effective suturing and closure of the aqueous leak. After a mean follow-up of 22.0 months, mean IOP increased from 2.9 ± 2.3 mmHg to 14.1 ± 3.3 mmHg, and mean VA improved from 20 ⁄ 50 to 20 ⁄ 30. Halkiadakis et al. (2005) employed the same technique in 14 patients. The preoperative IOP was 3.3 ± 2.6 mmHg, and the final IOP was 11.6 ± 3.4 mmHg after 10.1 ± 6.8 months. VA improved in 10 of 14 eyes. A second scleral patch graft revision was necessary in three eyes, but bleb leaks and hypotony resolved in all 14 eyes at last follow-up.

Resolution As IOP is normalized, the choroidal folds become flattened and may completely disappear. Residual changes in the retinal pigment epithelium may remain as a result of hyperplasia and hyperpigmentation. Fluorescein angiography may depict abnormal areas of hypo- and hyperfluorescence. The choroid and the sclera recover their original thickness, and the tortuosity and engorgement of the retinal vessels disappear. The prognosis for visual recovery apparently depends primarily on the duration of the hypotony. If retinal folds are induced by scleral shrinkage in response to low IOP, the restoration of the normal smooth architecture to the retina and Bruch’s membranes allows realignment of photoreceptors. If not treated promptly, prolonged hypotony may cause irreversible fibrosis within the retina, choroid or sclera, maintaining the choroid in a folded position (Jampel et al. 1992).

Conclusion Hypotony maculopathy is an uncommon complication of glaucoma filtering surgery, trauma and other anterior segment surgeries. Young age (Dellaporta 1948, 1950, 1954; Jampel et al. 1992; Stamper et al. 1992; Sun˜er et al. 1997; Palmberg 1998), myopia (Jampel et al. 1992; Stamper et al. 1992; Sun˜er et al. 1997; Palmberg 1998), primary filtering surgery (Sun˜er et al. 1997), systemic illnesses (Costa et al. 1993b) and elevated preoperative IOP (Stamper et al. 1992; Palmberg 1998) have been found to be associated with hypotony maculopathy. Early detection of the characteristic fundoscopic findings of hypotony and the search for its cause are fundamental because the visual deficit can be corrected through appropriate measures to restore normal IOP. The prognosis for VA recovery depends on several factors, including the duration of the hypotony. Delayed normalization of IOP may result in permanent macular chorioretinal changes and poor vision. This justifies an immediate recognition of the condition, identification of the cause and initiation of treatment.

Financial⁄proprietary interest The authors do not have any financial or proprietary interest in the drugs and instruments mentioned in this article.

References Bashford KP, Shafranov G & Shields MB (2004): Bleb revision for hypotony maculopathy after trabeculectomy. J Glaucoma 13: 256–260. Baum M & Weiss HS (1993): Argon laser closure of conjunctival bleb leak. Arch Ophthalmol 111: 438. Bell RW, Habib NE & O’Brien C (1997): Long-term results and complications after trabeculectomy with a single per-operative application of 5-fluorouracil. Eye 11: 663– 671. Bettin P, Carassa RG, Fiori M & Brancato R (1999): Treatment of hyperfiltering blebs with Nd:YAG laser-induced subconjunctival bleeding. J Glaucoma 8: 380–383. Bhende M, Lekha T, Vijaya L, Gopal L, Sharma T & Parrish S (1999): Ultrasound biomicroscopy in the diagnosis and management of cyclodialysis clefts. Indian J Ophthalmol 47: 19–23. Bindlish R, Condon GP, Schlosser JD, D’Antonio J, Lauer KB & Lehrer R (2002): Efficacy and safety of mitomycin-C in primary trabeculectomy: five-year follow-up. Ophthalmology 109: 1336–1341. Blok MD, Kok JH, van Mil C, Greve EL & Kijlstra A (1990): Use of the Megasoft Bandage Lens for treatment of complications after trabeculectomy. Am J Ophthalmol 110: 264–268. Budenz DL, Chen PP & Weaver YK (1999): Conjunctival advancement for late-onset filtering bleb leaks: indications and outcomes. Arch Ophthalmol 117: 1014–1019. Budenz DL, Schwartz K & Gedde SJ (2005): Occult hypotony maculopathy diagnosed with optical coherence tomography. Arch Ophthalmol 123: 113–114. Burnstein AL, WuDunn D, Knotts SL, Catoira Y & Cantor LB (2002): Conjunctival advancement versus nonincisional treatment for late-onset glaucoma filtering bleb leaks. Ophthalmology 109: 71–75. Buxton JN, Lavery KT, Liebmann JM, Buxton DF & Ritch R (1994): Reconstruction of filtering blebs with free conjunctival autografts. Ophthalmology 101: 635–639. Cangemi FE, Trempe CL & Walsh JB (1978): Choroidal folds. Am J Ophthalmol 86: 380–387. Cappaert WE, Purnell EW & Frank KE (1977): Use of B-sector scan ultrasound in the diagnosis of benign choroidal folds. Am J Ophthalmol 84: 375–379. Catoira Y, WuDunn D & Cantor LB (2000): Revision of dysfunctional filtering blebs by conjunctival advancement with bleb preservation. Am J Ophthalmol 130: 574–579.

595


Chan TK, Talbot JF, Rennie IG, Lonstaff S & Desai SP (2000): The application of ultrasonic biomicroscopy in the management of traumatic hypotony. Eye 14: 805–807. Cheung JC, Wright MM, Murali S & Pederson JE (1997): Intermediate-term outcome of variable dose mitomycin C filtering surgery. Ophthalmology 104: 143–149. Cohen SM, Flynn HW, Palmberg PF, Gass JD, Grajewski AL & Parrish RK II (1995): Treatment of hypotony maculopathy after trabeculectomy. Ophthalmic Surg Lasers 26: 435–441. Coleman J (1995): Evaluation of ciliary body detachment in hypotony. Retina 15: 312– 318. Collins ET (1917): Intra-ocular tension. I. The sequelae of hypotony. Trans Ophthal Soc UK 37: 281. Costa VP, Moster MR, Wilson RP, Schmidt CM, Gandham S & Smith M (1993a): Effects of topical mitomycin C on primary trabeculectomies and combined procedures. Br J Ophthalmol 77: 693–697. Costa VP, Smith M, Spaeth GL, Gandham S & Markovitz B (1993b): Loss of visual acuity after trabeculectomy. Ophthalmology 100: 599–612. Costa VP, Wilson RP, Moster MR, Schmidt CM & Grandham S (1993c): Hypotony maculopathy following the use of topical mitomycin C in glaucoma filtration surgery. Ophthalmic Surg 24: 389–394. Cristiansson J (1967): Ocular hypotony after fistulizing glaucoma surgery. Acta Ophthalmol (Copenh) 45: 837–845. Dellaporta A (1948): Uëber falten in der retina nach druckherabsetzenden operationen bei glaukom. Ophthalmologica 116: 51–60. Dellaporta A (1950): Fundus changes in postoperative hypotony. Am J Ophthalmol 40: 781–785. Dellaporta A (1954): Ueber fa¨ltelung der netzhaut bei hypotonie [creasing of retina in hypotonia]. Klin Monatsbl Augenh 125: 672–678. Deramo VA, Haupert CL, Fekrat S & Postel EA (2001): Hypotony caused by scleral buckle erosion in Marfan syndrome. Am J Ophthalmol 132: 429–431. Dickens MA & Cashwell LF (1996): Longterm effect of cataract extraction on the function of an established filtering bleb. Ophthalmic Surg Lasers 27: 9–14. Duker JS & Schuman JS (1994): Successful surgical treatment of hypotony maculopathy following trabeculectomy with topical mitomycin C. Ophthalmic Surg 25: 463–465. Ellong A, Mvogo CE, Bella-Hiag AL & Ngosso A (2001): Autologous blood injections for treating hypotonies after trabeculectomy. Sante 11: 273–276. Fannin LA, Schiffman JC & Budenz DL (2003): Risk factors for hypotony maculopathy. Ophthalmology 110: 1185–1191. Floyd BB & Minckler DS (1983): Increased vascular permeability in disc swelling produced by ocular hypotony. Exp Eye Res 36: 3–13. Foster CS, Stavrou P, Zafirakis P, Rojas B, Tesavibul N & Baltatzis S (1999): Intraocu-

596

lar lens removal from [corrected] patients with uveitis. Am J Ophthalmol 128: 31–37. Fourman S & Wiley L (1989): Use of a collagen shield to treat a glaucoma filter bleb leak. Am J Ophthalmol 107: 673–674. François J & DeLaey JJ (1971): Fluoro-angiographic aspects of acquired chorio-retinal folds. Mod Probl Ophthalmol 9: 129. Friberg TR & Grove AS Jr (1983): Choroidal folds and refractive errors associated with orbital tumors. An analysis. Arch Ophthalmol 101: 598–603. Gass JD (1972): Hypotony maculopathy. In: Bellows JG (ed.) Contemporary ophthalmology. Honoring Sir Stewart Duke-Elder. Baltimore: Williams & Wilkins 343–366. Gass JD (1981): Radial chorioretinal folds. A sign of choroidal neovascularization. Arch Ophthalmol 99: 1016–1018. Gass JD (1987): Folds of the choroid and retina. In: Gass JD (ed.) Stereoscopic atlas of macular diseases, 3rd edn. St. Louis: Mosby Company 221–234. Gnanaraj L, Lam WC, Rootman DR & Levin AV (2005): Endoscopic closure of a cyclodialysis cleft. J AAPOS 9: 592–594. Halkiadakis I, Lim P & Moroi SE (2005): Surgical results of bleb revision with scleral patch graft for late-onset bleb complications. Ophthalmic Surg Lasers Imaging 36: 14–23. Hammer ME & Grizzard WS (2003): Endoscopy for evaluation and treatment of the ciliary body in hypotony. Retina 23: 30–36. Harizman N, Ben-Cnaan R, Goldenfeld M, Levkovitch-Verbin H & Melamed S (2005): Donor scleral patch for treating hypotony due to leaking and ⁄ or overfiltering blebs. J Glaucoma 14: 492–496. Hatton MP, Duker JS, Reichel E, Morley MG & Puliafito CA (1998): Treatment of relapsed cytomegalovirus retinitis with the sustained-release ganciclovir implant. Retina 18: 50–55. Haynes WL & Alward WL (1999): Combination of autologous blood injection and bleb compression sutures to treat hypotony maculopathy. J Glaucoma 8: 384–387. Hill RA, Aminlari A, Sassani JW & Michalski M (1990): Use of a symblepharon ring for treatment of over-filtration and leaking blebs after glaucoma filtration surgery. Ophthalmic Surg 21: 707–710. Hutchinson AK, Grossniklaus HE, Brown RH, McManus PE & Bradley CK (1994): Clinicopathologic features of excised mitomycin filtering blebs. Arch Ophthalmol 112: 74–79. Hyvarinen L & Walsh FB (1970): Benign chorioretinal folds. Am J Ophthalmol 70: 14–17. Ichibe M, Yoshizawa T, Funaki S, Funaki H, Ozawa Y, Tanaka Y & Abe H (2002): Severe hypotony after macular translocation surgery with 360-degree retinotomy. Am J Ophthalmol 134: 139–141. Jampel HD, Pasquale LR & Dibernardo C (1992): Hypotony maculopathy following trabeculectomy with mitomycin C. Arch Ophthalmol 110: 1049–1050.

Kajiwara K (1990): Repair of a leaking bleb with fibrin glue. Am J Ophthalmol 109: 599–601. Kalina RE & Mills RP (1980): Acquired hyperopia with chorodial folds. Ophthalmology 87: 44–50. Kato T, Hayasaka S, Nagaki Y & Matsumoto M (1999): Management of traumatic cyclodialysis cleft associated with ocular hypotony. Ophthalmic Surg Lasers 30: 469–472. Kitazawa Y, Suemori-Matsushita H, Yamamoto T & Kawase K (1993): Lowdose and high-dose mitomycin trabeculectomy as an initial surgery in primary open-angle glaucoma. Ophthalmology 100: 1624–1628. Kokame GT, de Leon MD & Tanji T (2001): Serous retinal detachment and cystoid macular edema in hypotony maculopathy. Am J Ophthalmol 131: 384–386. Kroll AJ & Norton EW (1970): Regression of choroidal folds. Trans Am Acad Ophthalmol Otolaryngol 74: 515–526. Lanzl IM, Wilson RP, Dudley D, Augsburger JJ, Aslanides IM & Spaeth GL (2000): Outcome of trabeculectomy with mitomycin-C in the iridocorneal endothelial syndrome. Ophthalmology 107: 295–297. Lebuisson DA, Herbet-Frileux F, Aron JJ, Odievre M, Alagille D & Cotlier E (1981): Ocular manifestations accompanying congenital biliary duct hypoplasia. Bull Soc Ophtalmol Fr 81: 169–170. Leen MM, Moster MR, Katz LJ, Terebuh AK, Schmidt CM & Spaeth GL (1995): Management of overfiltering and leaking blebs with autologous blood injection. Arch Ophthalmol 113: 1050–1055. Martinez de la Casa JM, Garcia Feijoo J, Castillo Gomez A, Macias Benitez JM, Martin Valdizan C & Garcia Sanchez J (2003): Hypotony maculopathy diagnosed by optical coherence tomography. Arch Soc Esp Oftalmol 78: 567–569. Martinez Garcia A & Perez Garcia R (2000): Mitomycin C in open angle glaucoma surgery with previous failed glaucoma surgery. Arch Soc Esp Oftalmol 75: 449–454. Masaoka N, Sawada K, Komatsu T, Fukushima A & Ueno H (2000): Indocyanine green angiographic findings in 3 patients with traumatic hypotony maculopathy. Jpn J Ophthalmol 44: 283–289. Me´gevand GS, Salmon JF, Scholtz RP & Murray AD (1995): The effect of reducing the exposure time of mitomycin C in glaucoma filtering surgery. Ophthalmology 102: 84–90. Melamed S, Ashkenazi I, Belcher DC III & Blumenthal M (1991): Donor scleral graft patching for persistent filtration bleb leak. Ophthalmic Surg 22: 164–165. Melamed S, Ashkenazi I, Glovinski J & Blumenthal M (1990): Tight scleral flap trabeculectomy with postoperative laser suture lysis. Am J Ophthalmol 109: 303–309. Melamed S, Hersh P, Kersten D, Lee DA & Epstein DL (1986): The use of glaucoma shell tamponade in leaking filtration blebs. Ophthalmology 93: 839–842.


Mietz H, Jacobi PC & Krieglstein GK (2002): Intraoperative episcleral versus postoperative topical application of mitomycin-C for trabeculectomies. Ophthalmology 109: 1343–1349. Mietz H & Krieglstein GK (2001): Suramin to enhance glaucoma filtering procedures: a clinical comparison with mitomycin. Ophthalmic Surg Lasers 32: 358–369. Minckler DS & Bunt AH (1977): Axoplasmic transport in ocular hypotony and papilledema in the monkey. Arch Ophthalmol 95: 1430–1436. Morris AT & Sanders MD (1980): Macular changes resulting from papilloedema. Br J Ophthalmol 64: 211–216. Neelakantan A, Rao BS, Vijaya L, Grandham SB, Krishnan N, Priya VS & Murugeshan R (1994): Effect of the concentration and duration of application of mitomycin C in trabeculectomy. Ophthalmic Surg 25: 612–615. Newell FW (1973): Choroidal folds. The seventh Harry Searls Gradle Memorial Lecture. Am J Ophthalmol 75: 930–942. Newhouse RP & Beyrer C (1982): Hypotony as a late complication of trabeculectomy. Ann Ophthalmol 14: 685–686. Norton EW (1969): A characteristic fluorescein angiographic pattern in choroidal folds. Proc R Soc Med 62: 119–128. Nuyts RM, Felten PC, Pels E, Langerhorst CT, Geijssen HC, Grossniklaus HE & Greve EL (1994a): Histopathologic effects of mitomycin C after trabeculectomy in human glaucomatous eyes with persistent hypotony. Am J Ophthalmol 118: 225–237. Nuyts RM, Greve EL, Geijssen HC & Langerhorst CT (1994b): Treatment of hypotonous maculopathy after trabeculectomy with mitomycin C. Am J Ophthalmol 118: 322–331. O’Connor DJ, Tressler CS & Caprioli J (1992): A surgical method to repair leaking filtering blebs. Ophthalmic Surg 23: 336–338. Oppenheim B & Ortiz JM (1993): Hypotonous maculopathy after trabeculectomy with subconjunctival 5-fluorouracil. Am J Ophthalmol 115: 546–547. Oyakawa RT & Maumenee AE (1982): Clear-cornea cataract extraction in eyes with functioning filtering blebs. Am J Ophthalmol 93: 294–298. Palmberg P (1996): Late complications after glaucoma filtering surgery. In: Leader BJ & Calkwood JC (eds) Peril to the nerve – glaucoma and clinical neuro-ophthalmology. Proceedings of the 45th annual symposium of the New Orleans Academy of Ophthalmology. The Hague: Kugler, 183–193. Palmberg P & Zacchei A (1996): Compression sutures – a new treatment for leaking or painful filtering blebs. Invest Ophthalmol Vis Sci 37 (Suppl.): 444. Pau H (1950): Stauungspapille und netzhautfalten nach operativer hypotonie beim glaukom [Choked disk with plication of the retina as a result of postoperative hypotonia in glaucoma]. Klin Monatsbl Augenh 117: 591.

Pederson JE (1996): Ocular hypotony. In: Ritch R, Shields MB & Krupin T (eds) The glaucomas, 2nd edn. St. Louis: Mosby 385–395. Perkins TW, Gangnon R, Ladd W, Kaufman PL & Heatley GA (1998): Trabeculectomy with mitomycin C: intermediate-term results. J Glaucoma 7: 230–236. Rasheed el-S (1999): Initial trabeculectomy with intraoperative mitomycin-C application in primary glaucomas. Ophthalmic Surg Lasers 30: 360–366. Renard G (1946): Les aspects pathologiques du fond de l’oeil dans les affections de la re´tine. Paris: Masson et Cie E´diteurs. Roters S, Engels BF, Szurman P & Krieglstein GK (2002): Typical ultrasound biomicroscopic findings seen in ocular hypotony. Ophthalmologica 216: 90–95. Ruderman JM & Allen RC (1985): Simmons’ tamponade shell for leaking filtration blebs. Arch Ophthalmol 103: 1708–1710. Savage JA, Condon GP, Lytle RA & Simmons RJ (1988): Laser suture lysis after trabeculectomy. Ophthalmology 95: 1631–1638. Schwartz GF, Robin AL, Wilson RP, Suan EP, Pheasant TR & Prensky JG (1996): Resuturing the scleral flap leads to resolution of hypotony maculopathy. J Glaucoma 5: 246–251. Shields MB (1982): Combined cataract extraction and glaucoma surgery. Ophthalmology 89: 231–237. Shields MB, Scroggs MW, Sloop CM & Simmons RB (1993): Clinical and histopathologic observations concerning hypotony after trabeculectomy with adjunctive mitomycin C. Am J Ophthalmol 116: 673–683. Sibayan SA, Igarashi S, Kasahara N, Montenegro MH, Simmons RJ, Simmons RB & Smith TJ (1997): Cataract extraction as a means of treating postfiltration hypotony maculopathy. Ophthalmic Surg Lasers 28: 241–243. Sihota R, Dada T, Gupta SD, Sharma S, Arora R & Agarwal HC (2000): Conjunctival dysfunction and mitomycin C-induced hypotony. J Glaucoma 9: 392–397. de Smet MD, Gunning F & Feenstra R (2005): The surgical management of chronic hypotony due to uveitis. Eye 19: 60–64. Smith MF, Magauran RG III, Betchkal J & Doyle JW (1995): Treatment of postfiltration bleb leaks with autologous blood. Ophthalmology 102: 868–871. Stamper RL, McMenemy MG & Lieberman MF (1992): Hypotonous maculopathy after trabeculectomy with subconjunctival 5-fluorouracil. Am J Ophthalmol 114: 544–553. Stefansson E (2006): Ocular oxygenation and the treatment of diabetic retinopathy. Surv Ophthalmol 51: 364–380. Sun˜er IJ, Greenfield DS, Miller MP, Nicolela MT & Palmberg PF (1997): Hypotony maculopathy after filtering surgery with mitomycin C. Incidence and treatment. Ophthalmol 104: 207–214. Tannenbaum DP, Hoffman D, Greaney MJ & Caprioli J (2004): Outcomes of bleb excision and conjunctival advancement for leaking

or hypotonous eyes after glaucoma filtering surgery. Br J Ophthalmol 88: 99–103. Tomlinson CP, Belcher CD III, Smith PD & Simmons RJ (1987): Management of leaking filtration blebs. Ann Ophthalmol 19: 405–411. Toris CB & Pederson JE (1987): Aqueous humor dynamics in experimental iridocyclitis. Invest Ophthalmol Vis Sci 28: 477–481. Tsai JC, Chang HW, Kao CN, Lai IC & Teng MC (2003): Trabeculectomy with mitomycin C versus trabeculectomy alone for juvenile primary open-angle glaucoma. Ophthalmologica 217: 24–30. Volcker HE & Naumann GO (1979): Morphology of uveal and retinal edemas in acute and persisting hypotony. Mod Probl Ophthalmol 20: 34–41. Von Winning CHOM (1972): Fluography of choroidal folds. Documenta Ophthalmologica 31: 209. Weekers R & Delmarcelle Y (1953): Ocular hypotonia caused by reduction of aqueous flow. Ophthalmologica 125: 425–437. Westfall AC, Ng JD, Samples JR & Weissman JL (2004): Hypotonous maculopathy: magnetic resonance appearance. Am J Ophthalmol 137: 563–566. Whiteside-Michel J, Liebmann JM & Ritch R (1992): Initial 5-fluorouracil trabeculectomy in young patients. Ophthalmology 99: 7–13. Wilson MR & Kotas-Neumann R (1994): Free conjunctival patch for repair of persistent late bleb leak. Am J Ophthalmol 117: 569–574. Wise JB (1993): Treatment of chronic postfiltration hypotony by intrableb injection of autologous blood. Arch Ophthalmol 111: 827–830. Wolter JR (1974): Parallel horizontal choroidal folds secondary to an orbital tumor. Am J Ophthalmol 77: 669. Yieh FS, Lu DW, Wang HL & Chou PI (2001): The use of autologous fibrinogen concentrate in treating ocular hypotony after glaucoma filtration surgery. J Ocul Pharmacol Ther 15: 443–448. Zacharia PT, Deppermann SR & Schuman JS (1993): Ocular hypotony after trabeculectomy with mitomycin C. Am J Ophthalmol 116: 314–326. Zacharia PT & Schuman JS (1997): Combined phacoemulsification and trabeculectomy with mitomycin-C. Ophthalmic Surg Lasers 28: 739–744.

Received on September 26th, 2006. Accepted on January 23rd, 2007. Correspondence: Vital P. Costa Rua Bauru, 40 Saõ Paulo, SP 01248–010 Brazil Tel: +55 11 3865 9630 Fax: +55 11 3865 9630 Email: [email protected]

597