Clinical Case Notes. Recurrent posterior capsular opacification and capsulorhexis contracture after cataract surgery in myotonic dystrophy

Clinical and Experimental Ophthalmology 2004; 32: 651–655

Letters to the Editor

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Letters to the Editor

Clinical Case Notes

Orbital lymphoid tumour located within an extraocular muscle ABSTRACT A rare case of an orbital lymphoid tumour within an extraocular muscle is presented. The tumour displayed features of a progressive indolent systemic lymphoma. There was no response to a trial of chemotherapy and so local radiotherapy was instituted. At follow up 2 months later there was no evidence of disease. Key words: extraocular muscles, lymphoid tumour, neoplasia, orbit.

INTRODUCTION Lymphoid tumours are well-recognized to arise within the orbit, most commonly involving the lacrimal gland, orbital fat or conjunctiva. The case is presented here of an orbital lymphoproliferative mass that was unusually confined to an extraocular muscle (EOM).

CASE REPORT A 44-year-old woman was referred with a history of right lower lid swelling for 1 month. There were no other symptoms including no diplopia. The patient gave a history of atypical focal T-cell lymphomatous lesions involving the head and neck. Five years earlier, the patient presented with a mass lesion in her right temporalis muscle, which was shown to be a malignant non-Hodgkin’s T-cell lymphoma. The lesion was treated with local radiotherapy and the lesion resolved. Two years later a mass lesion was identified on computed tomography (CT) scan in the right supraglottic area following presentation with hoarseness. The lesion was biopsied and shown to histologically and immunologically match the temporalis muscle lesion. This lesion again resolved following a course of focal radiotherapy. At the time of the initial presentation, investigations for systemic lymphoma were negative. These included peripheral blood examinations, flow cytometry, bone marrow aspirate and trephine. At the time the supraglottic lesion was diagnosed, whole body gallium scan and SPECT were negative for systemic disease. Examination for the present complaint revealed a palpable firm smooth mass at the inferomedial aspect of the right orbit. Exophthalmometry measured 14 mm on the right and 13.5 mm on the left. There was no obvious displacement of the globe. Ocular rotations were full and there was no ptosis.

A CT scan showed enlargement of the right inferior oblique muscle. There was also diffuse thickening throughout the maxillary antra on the same side, extending into the nasal sinuses (Fig. 1). An inferior orbitotomy was performed to expose a grossly enlarged right inferior oblique muscle. The muscle and some adjacent fatty tissue were biopsied (Fig. 2). Histological examination of the specimen revealed muscle fibres separated by a dense infiltrate of lymphocytes of small size. The nuclei were generally rounded but some showed atypical nuclear membranes with larger nuclei. Mitotic activity was minimal. Immunohistochemical stains showed the majority of the cells to be CD3 positive (T-cells). Stains for immunoglobulins and light chains revealed no identifiable monoclonal population. It was concluded that the density of the infiltrate and its distribution in the skeletal muscle fibres implicated lymphoma. The specimen of fibro-adipose tissue was uninvolved. The appearances in the biopsy were similar to that seen in the two previous lesions. The tumour was classified as a peripheral T-cell lymphoma – unspecified, according to the WHO classification system. Because the tumour displayed features of a progressive indolent systemic lymphoma, the patient underwent a trial of chemotherapy consisting of two weekly cycles of cyclophosphamide 150 mg per day in conjunction with prednisolone 50 mg per day. However, after 2 months’ treatment there had been no response so local radiotherapy was instituted. The patient received a total of 30 cGy in 15 fractions using a wedge pair field to include inferior orbit, maxillary sinus and nasal cavity. At follow up 2 months later there was no evidence of disease.

Figure 1. Coronal computed tomography scan through orbits. Enlarged inferior oblique muscle (arrow) can be seen in the floor of the right orbit.

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Letters to the Editor In addition to being uniquely placed within an EOM, the lymphoma in our patient was also unusual because of its T-cell lineage and systemic involvement. The overwhelming majority (97%) of ocular adnexal lymphomas are of B-cell lineage9 and most (91%) present as localized stage IE disease (primary localised orbital lymphoma).10 Despite this, some will develop systemic disease with time. Several cases of orbital lymphoma within an EOM required long-term follow up before systemic disease was identified. One out of the 11 patients with an EOM lymphoma reported had succumbed to their systemic disease by the time of publication.2 This compares with a mortality rate of 24% for all ocular adnexal lymphopropliferative disease.9 Local radiotherapy has been recommended as the preferred method of treatment for orbital lymphoid tumours.2 In cases where restriction of upward gaze is a feature, orbital radiotherapy results in a complete return of upward gaze in most cases.2 This is probably due to the absence of fibrosis in lymphoid tumours of the EOM as compared with Graves’ orbitopathy and orbital myositis.

Figure 2. This photomicrograph of a H&E stain of the inferior oblique biopsy specimen from the patient demonstrates a diffuse small cell infiltrate that has completely replaced striated skeletal muscle. Most cells stained positive for CD3.

DISCUSSION This is a rare case of an orbital lymphoid tumour that was situated within an EOM as opposed to the more common sites of involvement such as the lacrimal gland, orbital fat or conjunctiva. We have been able to identify only 11 other cases in the literature where lymphoid tumour presented in this way.1–5 The most common presenting complaints reported were diplopia, lid fullness and ptosis,1–3 whereas pain, conjunctival vasocongestion or lid erythema were not typical features. Involvement of the superior rectus/levator muscle complex was seen in seven cases,2,3 with the medial rectus involved on two occasions2,4 and the lateral rectus in one case.1 This is the second description of orbital lymphoid tumour situated within the inferior oblique muscle. Two series with a combined total of 173 patients with enlarged EOM found the most common aetiology was Graves’ disease (66%).6,7 In these patients the inferior rectus was the most commonly involved and there is generally severe limitation of upgaze due to fibrosis. This contrasts with EOM lymphoma, where eye excursions are relatively preserved. Furthermore, a palpable orbital mass is typically absent in thyroid orbitopathy and there is lid retraction rather than ptosis following superior rectus-levator involvement. Orbital myositis, as part of the spectrum of idiopathic orbital inflammation, is the commonest cause of enlarged EOM after thyroid disease.6,7 The muscle swelling in orbital myositis is more acute in onset, with pain, proptosis, motility disturbance, lid erythema and conjunctival injection most prominent over the muscle insertions. Typically the muscle swelling from lymphoid infiltration is more massive than in myositis. The tissue involvement in both conditions may ‘spill over’ to involve adjacent orbital tissues, and the histopathological distinction may at times be difficult. Primary tumours of the EOM are rare and include rhabdomyosarcoma, granular cell tumour and liposarcoma. Solitary EOM metastases are rare, but have been reported from breast, lung, small cell carcinomas and malignant melanoma of the skin. EOM involvement may also occur in amyloidosis, and Trichinella spiralis.8

Gilda Kert FRANZCO,1 Colin I Clement MB BS PhD2 and Brett A O’Donnell FRANZCO2,3 1 Wickham Terrace, Brisbane, Queensland, and 2Royal North Shore Hospital and 3St Vincents Hospital, Sydney, New South Wales, Australia

REFERENCES 1. Yokoji H, Nakamura S, Ikeda T. A case of malignant lymphoma with metastasis to the lateral rectus muscle. Jap J Clin Neurol 1997; 37: 526–7. 2. Hornblass A, Jakobiek FA, Reifler DM, Mines J. Orbital lymphoid tumours located predominately within extraocular muscles. Ophthalmology 1987; 94: 688–97. 3. George JL, Quercia P, Hachet E, Humbert P, Plenat F. NonHodgkin’s malignant lymphoma of the rectus superior oculi muscle causing a deficit of the elevation. Bull Soc Ophth Fr 1986; 5: 721–4. 4. Arai N, Hara A, Umeda M, Shirai T. Non-Hodgkin’s lymphoma localised at the right ocular medial rectal muscle. Jap J Clin Haematol 1991; 32: 52–5. 5. Curutchet L, Gicquel JJ, Adenis JP, Dighiero P. [Lymphoma revealed by isolated obliquus inferior muscle involvement in exophthalmia.] J Fr Ophtalmol 2003; 26: 626–30 (in French). 6. Trokel SL, Hilal SK. Recognition and differential diagnosis of enlarged extraocular muscles in computed tomography. Am J Ophthalmol 1979; 87: 503–12. 7. Lacey B, Chang W, Rootman J. Non-thyroid causes of extraocular muscle disease. Surv Ophthalmol 1999; 44: 187–213. 8. Jakobiec FA, Font RL. Orbit. In: Spencer W, ed. Ophthalmic Pathology: an Atlas and Textbook, Vol. 3, 3rd edn. Philadelphia: WB Saunders Co, 1986; 2458–60. 9. Carbone PP, Kaplan HS, Musshof K, Smithers DW, Tubiana M. Report of the committe on Hodgkin’s disease staging classification. Cancer Res 1971; 31: 1860–61. 10. McKelvie PA, McNab A, Francis IC, Fox R, O’Day J. Ocular adnexal lymphoproliferative disease: a series of 73 cases. Clin Experiment Ophthalmol 2001; 29: 387–93.

Letters to the Editor

Recurrent posterior capsular opacification and capsulorhexis contracture after cataract surgery in myotonic dystrophy ABSTRACT Cataracts are well known to be associated with myotonic dystrophy. Less well known are the phenomena of recurrent posterior capsule opacification and capsulorhexis contracture post cataract surgery. Two cases are described herein of postoperative capsular complications requiring multiple capsulotomies in patients with myotonic dystrophy. It is proposed that a common aetiology may underlie both posterior capsule opacification and capsulorhexis contracture in myotonic dystrophy cases.

Key words: capsulorhexis, cataract, lens epithelium, myotonic dystrophy, posterior capsule.

INTRODUCTION Myotonic dystrophy is an autosomal dominant condition caused by an expansion of an unstable CTG repeat in the protein kinase gene (DMPK) on chromosome 19q13.3, resulting clinically in generalized muscle weakness, myotonia and frontal baldness. There are several well known ocular manifestations, including oculomotor weakness and cataracts, but only recently have recurrent posterior capsule opacification (PCO)1 and anterior capsulorhexis contracture (ACC)2,3 after cataract surgery been reported. We present two cases of these recurrent capsular complications following cataract surgery in myotonic patients.

CASE REPORTS Case 1 A 28-year-old man with known myotonic dystrophy presented in 1991 with progressive visual blurring. Visual acuities were 6/9 in the right and 6/60 in the left. There were bilateral anterior and posterior polychromatic dots and a posterior subcapsular lens opacity. He underwent uncomplicated consecutive cataract extraction and posterior chamber polymethylmethacrylate (PMMA) intraocular lens insertion (PC-IOL; Intraoptics, Australia, SK18UB, 19.5 D lens in each eye) in 1992. Ten months after left and 5 months after right cataract surgery, PCO was noted, requiring YAG laser capsulotomy in each eye. By 1995, PCO had effectively reformed bilaterally, causing a reduction in vision sufficient to necessitate further capsulotomies. This recurred on two further occasions in the right eye, and one further occasion in the left eye, necessitating multiple capsulotomies (Table 1).

Case 2 A 49-year-old Caucasian man with myotonic dystrophy and cataract reducing his visual acuity to 6/24 underwent uncomplicated left phacoemulsification and posterior chamber silicone IOL insertion (Allergan, USA, SI-40NB, 27.0 D) in April 2000. Two weeks postoperatively, left visual acuity had improved to 6/7.5. By

653 August 2000, left vision had deteriorated to 6/24, and left YAG capsulotomy was performed for PCO. Visual acuity then improved to 6/6. By July 2001, functional right visual acuity had deteriorated due to dense posterior subcapsular cataract despite Snellen acuity of 6/ 6. Right phacoemulsification and PC-IOL insertion (Allergan, USA, SI-40NB, 26.0 D) was performed, and despite initial improvement, by 4 weeks postoperatively vision deteriorated over a period of 2 weeks to 6/12. In addition, left vision had deteriorated markedly from 6/6 to count fingers at 0.5 m. In the left eye, there was prominent epithelial pearl formation in the posterior capsule, and marked contracture of both the posterior capsule and capsulorhexis. Left YAG posterior capsulotomy was performed, with a good result, but within 2 months, in October 2001, an anterior capsulotomy was required for ACC. At this time, marked right anterior capsular phimosis was noted for the first time, which required right YAG anterior capsulotomy (Fig. 1). Within a month, dramatic recurrence of anterior capsular opacification and contracture were noted in the left eye, and four anterior radial capsulotomies and a cruciate posterior capsulotomy were performed (Fig. 2). Following this, the visual axis was clear and visual acuity returned to normal. Over the following 18 months, recurrent anterior and posterior contractures necessitated further capsulotomies: three for the right eye and one for the left eye (Table 2).

DISCUSSION Posterior capsule opacification is a well-recognized complication of cataract surgery. It appears to be caused by the proliferation, migration and metaplasia of residual lens epithelial cells, and can manifest as capsular ‘fibrosis’, thought to be derived from anterior lens epithelium, or epithelial (Elschnig) ‘pearls’, thought to be derived from equatorial epithelium.4 Disruption of the blood–aqueous barrier or anterior segment inflammation after surgery may be the stimuli promoting this process,5,6 perhaps acting via cytokines.7 PCO is more common in young patients and those with uveitis or traumatic cataracts.4 PCO may directly decrease visual acuity, or indirectly cause folds in the posterior capsule or mechanical malposition of the IOL.4 Close contact of the lens capsule to the IOL may inhibit PCO, and this in turn is influenced by lens design and the type of optic material used.8 The influence of IOL material and capsule adhesion on rates of PCO is an area of enduring controversy, given the confounding influences of lens contour and edge design.9,10 Anterior capsulorhexis contracture is a complication of cataract surgery specific to the continuous curvilinear capsulorhexis method of anterior capsulotomy. Slight ACC occurs in most patients during the first 3 months after cataract surgery, but rarely is this severe enough to have visual significance.2 Severe ACC may significantly impair visual acuity after cataract surgery either through IOL decentration, or directly by obstruction of the visual axis. A capsulorhexis diameter of less than 2.3 mm may produce diffraction effects.2 Other rare complications of severe contracture include ciliary body detachment and retinal detachment.11,12 Lens epithelial cells at the anterior capsule margin may undergo fibrous metaplasia when in contact with the synthetic IOL, possibly mediated by cytokines.13 The most important risk factor for clinically significant ACC is a small capsulorhexis size at the time of cataract surgery.13–15 Contraction may be severe if opposed by

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Letters to the Editor

Table 1. Interventions in Case 1 Date January 1992 June 1992 November 1992 February 1995 April 1999 October 2000 May 2001 May 2003

Table 2. Interventions in Case 2

Right eye

Left eye

– Cataract surgery pc YAG pc YAG pc YAG pc YAG pc YAG –

Cataract surgery – pc YAG pc YAG – – – pc YAG

Date April 2000 August 2000 July 2001 August 2001 October 2001 November 2001 August 2002 December 2002 January 2003

Right eye

Left eye

– – Cataract surgery – ac YAG – ac YAG, pc YAG ac YAG, pc YAG ac YAG, pc YAG

Cataract surgery pc YAG – pc YAG ac YAG ac YAG, pc YAG – ac YAG, pc YAG –

pc, posterior capsulotomy; YAG, Nd:YAG laser. ac, anterior capsulotomy; pc, posterior capsulotomy; YAG, Nd:YAG laser.

Figure 1. Case 2 right eye. Anterior and posterior capsulotomy has been performed; note scarred anterior capsule and thickened posterior capsule leaves.

weak zonules.13 Other factors may include haptic materials and design, which vary in their ability to resist ACC.16 The reported associations of severe progressive constriction of the anterior capsulorhexis include pseudoexfoliation, uveitis, pars planitis, high myopia and retinitis pigmentosa. Myotonic dystrophy has recently been added to this list.3,11 It has been suggested that ciliary body atrophy in myotonic dystrophy may result in a relatively unopposed centripetal force at the capsulorhexis margin.17,18 Both PCO and ACC can be effectively treated using Nd:YAG laser capsulotomy, and recurrence is usually rare. The simultaneous finding of both recurrent PCO and ACC in a single patient with myotonic dystrophy may suggest a common aetiological factor, perhaps the propensity for lens epithelial cells in myotonic dystrophy to undergo an excessive fibroblastic, proliferative reaction following cataract surgery, associated with a greater than average contractility after metaplasia to myofibroblasts.2 Lens epithelial cells have recently been examined genetically in myotonic dystrophy patients, and the DMPK gene mutation was expressed in those cells.19 In addition, on histological examination of lens epithelium removed at the time of cataract surgery, lens epithelial density appeared to be decreased. It is currently unclear why a defect in the protein kinase gene should result in this pathological outcome.

Figure 2. Case 2 left eye. Radial anterior and cruciate posterior capsulotomy; despite currently clear visual axis, copious epithelial pearls on posterior capsular leaves are again beginning to occlude the axis from superiorly. We have provided two cases to support the association between myotonic dystrophy and recurrent PCO or ACC. Patients should be warned of the possibility that multiple capsulotomies may be required postoperatively. Elective use of a capsule tension ring may not prevent ACC.14 Recommendations as to IOL choice in myotonic dystrophy cataract patients remain speculative, due to ongoing controversy.10,20,21

Helen M Garrott MB BS,1,2 Mark J Walland FRANZCO1,2 and Justin O’Day FRANZCO2 1 Royal Melbourne Hospital and 2Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia

REFERENCES 1. Gjertsen IK, Sandvig KU, Eide N, Olsen BA. Recurrence of secondary opacification and development of a dense posterior vitreous membrane in patients with myotonic dystrophy. J Cataract Refract Surg 2003; 29: 213–16.

Letters to the Editor 2. Newman DK. Severe capsulorhexis contracture after cataract surgery in myotonic dystrophy. J Cataract Refract Surg 1998; 24: 1410–12. 3. Hansen SO, Crandall AS, Olson RJ. Progressive constriction of the anterior capsular opening following intact capsulorhexis. J Cataract Refract Surg 1993; 19: 77–82. 4. Apple DJ, Solomon KD, Tetz MR et al. Posterior capsule opacification. Surv Ophthalmol 1992; 37: 73–116. 5. Fagerholm P. The response of the lens to trauma. Trans Ophthalmol Soc UK 1982; 102: 369–74. 6. Miyake K. Blood–retinal barrier in long-standing aphakic eyes after extra- and intracapsular lens extractions. Graefes Arch Clin Exp Ophthalmol 1985; 222: 232–3. 7. Nishi O, Nishi K, Wada K, Ohmoto Y. Expression of transforming growth factor (TGF)-α, TGF-β2 and interleukin 8 messenger RNA in postsurgical and cultured lens epithelial cells obtained from patients with senile cataracts. Graefes Arch Clin Exp Ophthalmol 1999; 237: 806–11. 8. Clark D. Posterior capsule opacification. Curr Opin Ophthalmol 2000; 11: 56–64. 9. Oshika T, Nagata T, Ishii Y. Adhesion of lens capsule to intraocular lenses of polymethylmethacrylate, silicone and acrylic foldable materials: an experimental study. Br J Ophthalmol 1998; 82: 549–53. 10. Hollick EJ, Spalton DJ, Ursell PG et al. The effect of polymethylmethacrylate, silicone, and polyacrylic intraocular lenses on posterior capsular opacification 3 years after cataract surgery. Ophthalmology 1999; 106: 49–54. 11. Davison JA. Capsule contraction syndrome. J Cataract Refract Surg 1993; 19: 582–9. 12. Lanzl IM, Kopp C. Ciliary body detachment caused by capsule contraction. J Cataract Refract Surg 1999; 25: 1412–14.

655 13. Joo C-K, Shin J-A, Kim J-H. Capsular opening contraction after continuous curvilinear capsulorhexis and intraocular lens implantation. J Cataract Refract Surg 1996; 22: 585–90. 14. Moreno-Montanes J, Sanchez-Tocino H, Rodriguez-Conde R. Complete anterior capsule contraction after phacoemulsification with acrylic intraocular lens and endocapsular ring implantation. J Cataract Refract Surg 2002; 28: 717–19. 15. Kato S, Suzuki T, Hayashi Y et al. Risk factors for contraction of the anterior capsule opening after cataract surgery. J Cataract Refract Surg 2002; 28: 109–12. 16. Gonvers M, Sickenberg M, van Melle G. Change in capsulorhexis size after implantation of three types of intraocular lenses. J Cataract Refract Surg 1997; 23: 231–8. 17. Burns CA. Ocular histopathology of myotonic dystrophy; a clinicopathologic case report. Am J Ophthalmol 1969; 68: 416–22. 18. Hayasaka S, Kiyosawa M, Katsumata S et al. Ciliary and retinal changes in myotonic dystrophy. Arch Ophthalmol 1984; 102: 88–93. 19. Abe T, Sato M, Kuboki J et al. Lens epithelial changes and mutated gene expression in patients with myotonic dystrophy. Br J Ophthalmol 1999; 83: 452–7. 20. Cochener B, Jacq P-L, Colin J. Capsule contraction after continuous curvilinear capsulorhexis: poly (methyl methacrylate) versus silicone intraocular lenses. J Cataract Refract Surg 1999; 25: 1362–9. 21. Ursell PG, Spalton DJ, Pande MV. Anterior capsule stability in eyes with intraocular lenses made of poly (methylmethacrylate), silicone, and AcrySof. J Cataract Refract Surg 1997; 23: 1532–8.