CASE REPORT

A 12 year old girl was referred to Moorfields Eye Hospital for a second opinion regarding her deteriorating vision following bilateral trabeculectomies with adjuvant mitomycin C for raised intraocular pressure.

At the age of 5 years, she was diagnosed as having megalocornea with ocular hypertension. Two years later, because of the persistent degree of IOP elevation (between 30–40 mm Hg), she was commenced on bilateral medical treatment. However, at the age of 11, she developed such severe problems with her topical treatment that surgery was considered necessary. In May 1996 right and subsequently left trabeculectomies were performed and during the procedures subconjunctival mitomycin C (0.3 mg/ml) was applied for 5 minutes. Her postoperative recovery was complicated by the development of ocular hypotony.

She was seen at Moorfields for the first time with progressive bilateral vision loss and recent onset of transient obscurations, 5 months after her filtration surgery and the onset of hypotony. Her visual acuities had fallen from right eye 20/20 (−0.5/−0.25 × 180°) to hand movements (HM), and left eye 20/30 (−1.5 DS) to counting fingers (CF). Her visual fields on confrontation with a red target showed an enlarged blind spot. Both eyes had large, draining, diffuse and avascular filtration blebs with signs of hypotony as evidenced by bilateral IOPs of 0 mm Hg, superficial corneal epithelial staining striae, and macular and choroidal folds. Both optic discs were swollen although no haemorrhages or cotton wool spots were observed. The patient was sensitive to light and good quality photographs could not be obtained. An ultrasound showed bilateral anterotemporal choroidal detachments involving the ciliary body (right larger than left) and axial lengths recorded as 23.0 mm in both eyes.

She underwent several surgical procedures. The day after she first presented, she underwent a right subconjunctival autologous blood injection to the right bleb under general anaesthesia. The following day, however, her vision was worse with visual acuities being recorded as patchy areas of perception of light on the right and hand movements temporally on the left. Her IOPs were 4 and 0 mm Hg in the right and left respectively, and a greater degree of disc swelling (as judged by further elevation of the disc) was noted bilaterally. It was considered by a neurologist (GTP) that the disc swelling may itself be contributing to the visual loss, particularly in view of the transient visual obscurations which suggested critically impaired perfusion of the disc. To prevent even further vision loss, a lumbar puncture to reduce the CSF pressure was suggested, to provide short term improvement in disc perfusion, which it was hoped in the longer term would be helped by raising her intraocular pressure. She underwent further surgery to both her eyes for hypotony, later that evening, which comprised revision of both blebs with scleral patch grafts. This was preceded by a lumbar puncture under general anaesthesia at which there was an opening pressure of 22.5 cm H₂O. A volume of 30 ml of CSF was removed and the closing pressure was recorded as 5.5 cm H₂O with microbiological and biochemical analysis of CSF revealing no abnormality

The day after surgery, the fourth day after initial presentation, examination revealed improved visual acuities of HM in both eyes with IOPs of 19 and 23 mm Hg in the right and left eye respectively. The disc swelling was felt to be reduced, and over the next few days improved gradually. Seven days after presentation, her IOPs had fallen to 0 and 8 mm Hg, right and left, respectively, and she was taken back to theatre for anterior chamber refilling with Healon-GV. Her IOPs normalised to around 20 mm Hg again 10 days later, with decreasing disc swelling, and a repeat ultrasound showed reduced choroidal detachments and axial lengths of 24.8 mm in the right and 24.6 mm in the left.

She underwent one other further surgical procedure, 7 weeks after presentation, when her IOPs became elevated again at 35 and 28 mm Hg right and left respectively, to a degree where it was felt her optic discs would be compromised. Treatment consisted of needling procedures to both blebs with subconjunctival injections of 5-fluorouracil to reduce scar formation. Her IOPs responded very quickly to this final procedure and she remains on no antiglaucoma medication with normal intraocular pressures (less than 20 mm Hg) now 7 months after presentation. Both drainage blebs are Seidel negative with good evidence of aqueous drainage into the filtration blebs (Fig 1, top right). Her visual acuities and visual function have now recovered quite substantially. However she does has a relative afferent pupillary defect in the left eye, and her current refraction and visual acuities are right eye −1.0/−4.0 × 05° (RVA 20/30) and left eye −1.75/−6.5 × 180° (LVA 20/120). Her optic discs show no evidence of swelling, and she has neither choroidal detachments nor macular folds (Fig 1, bottom left and right) as confirmed on ultrasound.

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Figure 1

Although neonatal examination had been normal, our patient had been noted to have “large eyes” as a young child, as shown in this photograph taken at age 2 years (top left). Reversal of ocular hypotony occurred following filtration bleb revision with scleral patch grafts, with drainage into blebs apparent at 2 months (top right) postoperatively. Hypotony induced papilloedema resolved after surgery with no disc swelling apparent in right (bottom left) or left (bottom right) fundi, shown 7 months postoperatively.

COMMENT

This young girl presented to us with severe ocular hypotony following bilateral primary glaucoma filtration surgery with mitomycin C. She developed vision loss, with episodes of transient obscurations attributable to hypotony and disc swelling. Her response to the initial surgery and subsequently to the corrective surgical procedures made us suspect that she had an inherent problem in wound healing and scleral rigidity, especially as she displayed such dramatic changes in axial lengths (1.6–1.8 mm difference in pre- and postoperative lengths). We therefore wondered if she had an underlying connective tissue disorder.

She was found to have Ehlers-Danlos syndrome type II (EDS II). Examination revealed her to have joint hypermobility (Fig 2), with a high joint hypermobility score (Table 1)1 of 7/9. In addition, she showed evidence of skin striae in the lumbar region, thighs and breasts with a papyraceous scar on her right knee, and gave a history of bruising easily with prolonged bleeding when cut. Echocardiography however was normal, with a normal palate, no spinal defects, no arachnodactyly, and a normal arm span to height ratio. However, there was a strong family history of joint hypermobility.

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Figure 2

Our patient demonstrates joint hypermobility, a feature of Ehlers-Danlos syndrome. She can appose both thumbs to the flexor aspect of her wrist (top left), fold her fingers one over the other (top right), bend over to place her palms flat on the floor keeping her knees extended (bottom left), and put her ankles around her head (bottom right).

EDS is a heterogeneous group of genetically determined disorders of connective tissue affecting skin, ligaments, joints, blood vessels, and internal organs, of which at least nine subtypes exist, with the following diagnostic triad: extensible skin (extreme examples being described in fairground artistes, such as the “elastic skin man” of the 19th century), connective tissue fragility, and hypermobile joints.2 Although ocular complications in EDS are mostly associated with EDS type VI, a few ocular problems in EDS II have been documented such as prominent epicanthal folds, redundant skin on the upper eyelid, blue sclera, and the absence of periorbital fat.

The wound healing process in EDS II is known to be abnormal in the skin because of the anomalous development of scar formation due to aberrant collagen fibrils.3 An abnormal healing response to the initial filtration surgery in this young girl might have been exaggerated with the use of mitomycin C. Cutaneous wounds in EDS II initially appear with gaping edges—so called “fish mouths” and heal slowly, and when scar formation eventually occurs, are characteristically shiny and stretched—papyraceous. Our findings on initial exploration of the surgical site in the eye, in this case, revealed a friable, disintegrating scleral flap which would have permitted unguarded passage of aqueous into the subconjunctival space—hence the occurrence of hypotony when combined with a non-healing conjunctiva.

Ocular hypotony is associated with various complications4 including hypotonous maculopathy, resulting in a permanent reduction in vision and acuity. This occurrence has previously been attributed to reduced scleral rigidity, as seen in young and myopic eyes5 where a reduction in axial length has been documented following filtration surgery.6 Another mechanism put forward for the vision loss in these eyes, has been compression of the submacular sclera due to the resting tone of the inferior oblique muscle and decreased scleral rigidity.7

The incidence of post filtration ocular hypotony following full thickness procedures is 17–41%.4 This incidence was reduced significantly with the advent of guarded, partial thickness techniques, but the recent introduction of antiscarring agents such as mitomycin C and 5-fluorouracil5 6 has led to its increase once again. We believe that our patient had a complex and extreme response to filtration surgery with adjuvant mitomycin C complicated by her reduced scleral rigidity secondary to EDS II, as evidenced by her large eyes and marked changes in axial length in association with reduction in intraocular pressure.

The development of severe vision loss in our patient was associated with the occurrence of transient obscurations and hypotonous disc swelling. Resolution of the disc swelling was 4–6 weeks after correction of the hypotony, and improvement in visual acuity was noted thereafter. Its natural history—that is, the pattern of resolution and visual recovery, is compatible with disc swelling. Visual loss associated with hypotonous maculopathy, however, may never recover despite reversal of hypotony.6 Prolonged disc swelling in ocular hypotony is a recognised complication that is fortunately very rare. Experimental models have suggested that axoplasmic transport is delayed in cases of hypotony induced optic disc swelling giving rise to the same features histologically as seen with raised intracranial pressure papilloedema —for example, axonal swelling, accumulation of mitochondria, and cytoid body (cotton wool spots) formation.8 The pathogenesis of disc swelling in ocular hypotony may be related to that occurring in raised intracranial pressure if it is postulated that in both situations the CSF pressure in the subarachnoid space around the optic nerve exceeds the perfusion pressure of the optic disc. Therefore in our patient, it was considered that lowering the CSF pressure to well below normal levels (<20 mm H₂O) might provide temporary improvement in optic disc perfusion—hence our target for a very low closing pressure of 5.5 mm H₂O in the lumbar puncture. Two previous reports of unilateral disc swelling following trabeculectomy also suggest that optic disc oedema could result from a disturbed equilibrium between ICP and IOP—though none of the patients described in these papers had hypotony or profound vision loss.9 10

The development of profound vision loss in association with hypotony induced optic disc swelling in our patient, was as a complication of mitomycin C assisted glaucoma filtration surgery. However, the degree of hypotony was most probably related to reduced scleral rigidity. We believe that her abnormal wound healing response and defective connective tissue contributed to the severity of the hypotony that followed initial surgery with mitomycin C. We suggest that antiproliferatives be used with extreme caution in patients who you suspect may have a connective tissue disorder. A quick screening procedure might include a joint hypermobility score as shown in Table1. Patients with Ehlers-Danlos syndrome, such as our patient, may be at high risk of post filtration hypotony and developing “soft eyes” with sight threatening sequelae, as our case suggests that not only might they have elastic skin but also “elastic globes”.