Management of Symptomatic Meesmann Dystrophy.12

1040-5488/09/8610-1202/0 VOL. 86, NO. 10, PP.E1202–E1206 OPTOMETRY AND VISION SCIENCE Copyright © 2009 American Academy of Optometry CASE REPORT Management of Symptomatic Meesmann Dystrophy Isabelle Jalbert* and Fiona Stapleton† Abstract Meesmann dystrophy is a non-progressive autosomal dominant corneal epithelial dystrophy characterized by intraepithelial cysts, which is likely to be caused by an intraepithelial metabolic abnormality. Cases may be asymptomatic or be associated with symptoms of irritation, lacrimation, and photophobia. Palliative treatment includes ocular lubricants, cycloplegia, and therapeutic contact lenses. In severe cases, management with epithelial debridement, phototherapeutic keratectomy, and lamellar keratoplasty has been advocated. Most recently, the genetic and molecular basis of Meesmann dystrophy have been explored, and mutations in the genes encoding corneal epithelial keratins have been reported. This report describes a case of Meesmann dystrophy with unusually severe symptoms and punctate epithelial keratopathy managed with a therapeutic contact lens. (Optom Vis Sci 2009;86:E1202–E1206) Key Words: Meesmann dystrophy, confocal microscopy, corneal epithelium, microcysts, bandage contact lens orneal dystrophies are a group of inherited corneal diseases that are typically bilateral, symmetric, slowly progressive, and without relationship to environmental or systemic factors.1 The classic classification is on the basis of the corneal layer involved. In this report, a case of Meesmann epithelial dystrophy with late onset of symptoms and first diagnosis in a mature adult is described. The diagnosis and management of Meesmann dystrophy are discussed. C CASE REPORT A 43-year-old white women presented for the first time to our clinic with complaints of slight redness, foreign body sensation, light sensitivity, and slightly reduced vision in the right eye for the past year. The symptoms were worse on awakening and had gradually increased in intensity over the past 12 months. By the time she was seen in our clinic, she was acutely light sensitive, having to wear sunglasses indoors. She had consulted several practitioners during that time and was prescribed at various times topical dexamethasone 0.1%, prednisolone 0.5%, and acyclovir 3%, none of which successfully relieved her symptoms. She was currently using topical lubricants as required (Refresh Tears, Allergan, Irvine, CA), *OD, PhD, FAAO † MCOptom, PhD, FAAO School of Optometry and Vision Science, The University of New South Wales (IJ, FS), The Vision Cooperative Research Centre (IJ, FS), and The Institute for Eye Research, Sydney, Australia (IJ, FS). Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.optvissci.com). which provided limited relief. She had recently been diagnosed with depression and prescribed citalopram 20 mg qd. She had never worn spectacles. Her previous ocular history was unremarkable, however, she had never had her eyes examined until the onset of symptoms in the last year. Her mother in the United Kingdom had suffered from an unusual eye condition requiring regular visits to an ocular specialist but as she was now deceased, no further information was available. Visual acuity was measured at 6/6 “slow” right eye and 6/6 2 left eye. Pupils were equal, round, reactive to light, and accommodation in both eyes. Slit lamp examination of the right eye revealed moderate nasal and temporal limbal redness grade 2. Numerous ( 100) small intraepithelial cysts were noted to be scattered throughout the entire cornea but denser centrally. No stromal involvement and no infiltrates were observed (see Video, Supplemental Digital Content 1, which provides a composite view of the cysts and underlying normal stroma, http://links.lww.com/OPX/A10). The epithelial surface appeared roughened and negative staining was observed overlying some of the epithelial cysts. The anterior chamber was quiet. Fig. 1 illustrates the ocular signs of the right eye on slit lamp examination. The left conjunctiva was normal and white. A smaller number of intraepithelial cysts were detected in the midperiphery and periphery of the inferior left cornea. The epithelium was clear centrally and no corneal staining was visible. As in the right eye, no stromal involvement or infiltrates were noted, and the anterior chamber was quiet. Confocal microscopy (Confoscan 2, Fortune Technologies, Virgona, Italy) was performed on both corneas and revealed dense brightly reflective structures of about 15 m in size in the basal epi- Optometry and Vision Science, Vol. 86, No. 10, October 2009 photophobia. photophobia. EBMD. recurrent corneal erosion (RCE). subepithelial infiltrates were noted in both corneas and lid roughness was substantially increased in the right palpebral conjunctiva. bullous kerapathy in Fuchs disease. At the 2-month follow-up visit. A history of RCEs and/or previous episodes of acute pain are also more highly suggestive of EBMD. was not present here.3 Adenoviral keratoconjunctivitis subsequently causes multiple subepithelial infiltrates that are not characteristic of Meesmann disease. Contact lens wear was temporarily discontinued for Optometry and Vision Science. was not present.5 Such vesicles will. The differential diagnosis for Meesmann dystrophy includes epithelial basement membrane dystrophy (EBMD). however. and granular and do not have the vesicular cystic appearance associated with Meesmann. are coarse. which did not occur in this case. An extended wear schedule was prescribed to provide ongoing symptomatic relief. HSV keratitis is often classified into several subtypes based on clinical presentation. 2). which may have given rise to the recurrent erosions. coalesce and form the typical dendritic and geographic ulcers within hours or days of first examination. an idiopathic chronic superficial punctate keratitis. A history of recent upper respiratory tract infection. however. The epithelial microcysts tend to be localized in EBMD. lid swelling. a silicone hydrogel contact lens was fitted in the right eye: Purevision (Bausch & Lomb. thelium (Fig. 10. Multiple intraepithelial cysts extending from limbus to limbus best visualized using slit lamp biomicroscopy reverse illumination. adenoviral keratoconjunctivitis. No. This provided immediate and sustained relief of symptoms.Management of Symptomatic Meesmann Dystrophy—Jalbert and Stapleton E1203 FIGURE 1. Although the severe photophobia and the increased symptoms on awakening reported in this case can be suggestive of RCE. Other causes of microcystic edema such as contact lens-induced hypoxia6 or toxic edema must also be excluded. foreign body sensation. FIGURE 2.50 DS. En-face confocal microscopy image (350 450 m) showing dense brightly reflective structures ( 15 m) in basal epithelium. Right eye. and reduced vision associated with punctate epithelial keratitis.2. redness.2 A history of exacerbations followed by complete remission of symptoms is also more characteristic of Thygeson’s. infectious epithelial keratitis typically presents with symptoms of mild discomfort. 86.3 The early stage keratitis associated with adenoviral keratoconjunctivitis could also be mistaken for Meesmann dystrophy as it initially presents with bilateral tearing. The epithelial lesions in Thygeson’s.optvissci. however.2 RCE forms part of the differential diagnosis in this case as mild RCE may present without a frank epithelial defect and with epithelial microcysts only. A color version of this figure is available online at www. A viral corneal infection was suspected.2 None of these patterns were present in this case. which usually precedes adenoviral disease. small raised corneal vesicles may be similar in appearance to Meesmann dystrophy. and microcystic edema. Rochester. The patient reported also having recently suffered from a miscarriage. On the basis of corneal appearance and symptoms. there were no signs of stromal swelling or endothelial gutatta.70 mm. Right eye. watering. On the basis of the rationale that the highest possible oxygen transmissibility should be provided. 8. The first of these subtypes. NY) 0. Meesmann dystrophy was diagnosed. There was no history of previous contact lens wear or toxic exposure in this case. Thygeson’s keratitis. and tearing. Vol. Thygeson’s keratitis. or whorled fingerprint-like lines in one or both eyes. RCE occurs not only as a result of EBMD but also when an ab- normally weak attachment between the basal cells and the basement membrane of the epithelium is present. A smoother epithelial surface was noted at the 1-week follow-up visit as evidenced by a reduction in the levels of negative staining observed.com. a prior history of trauma. October 2009 . Although our patient reported worsening of symptoms on waking.4. distinct. herpes simplex (HSV) keratitis. will often show more than one type of corneal lesions including dot-like opacities. The subject’s 7-year-old daughter was examined and no corneal abnormalities could be detected. subepithelial map-like patterns. and blurred vision and in its early stages. The bulk of the intraepithelial cysts in Meesmann dystrophy are not raised and will typically cover a larger area of cornea than HSV vesicles. EBMD (Cogan microcystic or map-dot-fingerprint dystrophy) may be confused with Meesmann dystrophy as epithelial microcysts are one of the possible corneal signs of EBMD and typical age of onset is early adulthood. Bullous keratopathy in late stage Fuchs endothelial dystrophy may present similar symptoms to Meesmann dystrophy of pain and discomfort worse on awakening and the presence of persistent microcysts in the epithelium. 3). A therapeutic contact lens was prescribed for the relief of symptoms (Fig. commonly affects young adults and is characterized by recurrent attacks of irritation. transmission is autosomal dominant with either incomplete penetrance and/or delayed onset of phenotypic expression. GA) 0. CIBAVision) was recommended for the disinfection of the contact lenses on nightly removal. Denmark.16 –18 have been shown to occur in the two responsible genes suggesting that Meesmann is possibly more widespread than originally described.16 the Netherlands.8.E1204 Management of Symptomatic Meesmann Dystrophy—Jalbert and Stapleton FIGURE 3.optvissci.8 –10 conjunctival injection. Right eye.com.8 and blepharospasm.6 mm with an aqua #2 tint (tinted pupil) in the right eye.12 This case provides a good example of such disconnect between the corneal appearance and the reported symptoms.2. Irvine.8.8. Austria. although slight subepithelial opacities. A peroxide-based care system (AOSept. Corneal changes include microcystic epithelial opacities.10 the United States. After 1 month.11 however.10 It may therefore seem surprising that an earlier diagnosis was not suggested in this case. she had not had regular ocular examinations. However.10. mutations in these genes translate in a highly disorganized epithelium with thickening of the epithelium Optometry and Vision Science. DISCUSSION Meesmann dystrophy was first described by Meesmann in 1938. Over the next 6 month.15 and this may be the case here.8 the peripheral cornea. 86. management included a combination of lubrication therapy: Cellufresh as required during the day and Viscotears nocte as required and intermittent contact lens wear during periods of exacerbation of the symptoms. Atlanta. A color version of this figure is available online at www. Transgenic mice studies have confirmed the role of K12 in corneal epithelial fragility. and vortex-like opacities have occasionally been observed. The only family member available for examination was her 7-year-old daughter.8 Less often. We speculate that rupture of cysts and exposure of corneal nerve endings was the underlying mechanism for the severe pain and photophobia reported by our patient. France. 10. and sorbitol preserved carbomer 980 lubricating gel was prescribed at bedtime (Viscotears liquid gel.15 Taiwan. As high-oxygen permeability silicone hydrogel contact lenses with lower modulus become available. October 2009 . the levels of negative or positive staining observed during the visits remained very low.10 glare and/or photophobia.10. The corneal appearance remained identical during that time with no progression of the epithelial dystrophy.10.8 –10 reduced vision. CA).8. specific regions of the epithelium are affected such as the upper third.7 Symptoms commonly include ocular irritation or foreign body sensation. Meesmann dystrophy is geographically widespread with reports of cases in Germany. however.9. Vol. Switzerland. these may present a useful option for this patient.9 or a central diseased zone surrounded by a ring of clear epithelium and peripheral microcystic epithelium.18 In this case. It is possible that these cysts ruptured on waking and had recovered by the time the patient was seen in our office. respectively (OMIM 12210019).7. Meesmann dystrophy is generally described as non-progressive8 but significant worsening of symptoms with age as in this have been reported.8. the familial history was difficult to ascertain. severe pain is infrequently reported. Atlanta. No.14 Age of onset of the intraepithelial cysts seems to be early childhood with cases described in infants as young as a few months old. this product has much lower oxygen transmissibility than the PureVision (Dk/t of 110).18 Recent advances in genetic techniques have allowed the molecular basis of Meesmann corneal dystrophy to be elucidated. The K12 and K3 cornea specific keratins form the intermediate filament cytoskeleton of corneal epithelial cells.15. the corneal sensitivity to the rupturing of the cysts may change over time. although a single case of unilateral Meesmann dystrophy has been reported.8 Irregularly shaped areas of clear epithelium have also been described. Delayed or late onset cases have also been described.11 The intensity of symptoms reported in the same families varies from asymptomatic to extreme photophobia and symptoms may be disproportionate to the corneal signs.8.10 The demarcation between diseased and normal epithelium is sharp. typically (up to 85% of cases) involving the entire epithelium as far as the limbus. With a nominal Dk/t of 10. Preservative free unit dose carmellose sodium containing lubricating eyedrops were prescribed for use as required (Cellufresh. The disease seems to be bilateral. as the patient was emmetropic and had been asymptomatic up until a year ago. Lubrication therapy was commenced.11 It is possible that more cysts rupture with time leading to increased symptoms or alternatively.50 DS. 1 month until resolution of the infiltrates was noted.11.13 The corneal stroma is typically clear. Meesmann dystrophy has been ascribed to mutations in the cytokeratin 12 (K12) and/or the cytokeratin 3 (K3) genes on chromosomes 17q and 12q. Once mutation has occurred. Allergan. A therapeutic contact lens provided significant symptomatic relief.8 –10 tearing. CIBAVision. the UK (Northern Ireland). who was unaffected. The patient was instructed to continue self-managing the condition on the basis of her symptoms. corneal scarring.12 and Japan. 8.19 One study suggested that mutations in the K12 gene may be associated with a more severe phenotype of Meesmann dystrophy than K3 mutations. A tinted contact lens was prescribed to provide further relief from the ongoing photophobia.20 Ultrastructurally.17 Saudi Arabia.2 The epithelial microcysts are best observed on retroillumination. and a regular 6-month follow-up was scheduled.8 The intraepithelial cysts are typically rounded but can be more irregular8 and are roughly uniform in size. A daily wear schedule was prescribed with Viscotears liquid gel (CIBA Vision) nocte as required.9 Rupture of the cysts may cause the onset of symptoms. GA). a softer modulus contact lens was fitted: CibaSoft (CIBAVision.17 Several different mutations10 –12. Intrafamilial variation between individuals is common both in clinical appearance and symptoms reported. 15. Rapuano CJ. and acyclovir) prescribed in the 12 month before presentation. Patel DV. New York: Elsevier Butterworth-Heinemann.21:117–20. 2009.2. Swensson O. Management of Meesmann dystrophy typically requires minimal intervention with treatment other than lubrication not being normally required. Sutphin J. Ophthalmomyiasis.86:40–4. suggesting some environmental influences or interference from other disease-modifying genes. therapeutic contact lenses can be an excellent treatment option in more symptomatic cases as demonstrated here. A novel keratin 12 mutation in a German kindred with Meesmann’s corneal dystrophy. Busin M. This case presented with unusually intense symptoms.11. Weiss JS. Hypertonic agents (e. Her 2-year-old daughter also suffered from extreme photophobia and constant tearing and was reportedly unable to leave home without wearing a hat and sunglasses.22 Autologous stem cell trans- 2. 86. Bredrup C. Belin MW. Kivela T. Schlotzer-Schrehardt U. Ehlers N. 11. Kim EK. McLean WH.22 plantation appeared successful in the short term for the single unilateral Meesmann dystrophy case. Br J Ophthalmol 2004.24:669–73. Classification of herpes simplex virus keratitis and anterior uveitis. Cornea 2005.Management of Symptomatic Meesmann Dystrophy—Jalbert and Stapleton E1205 and its basement membrane and the presence of surface intraepithelial cysts. Warren JF.18:127–43.77:582–5. 52:154–6. Received February 21. October 2009 . Basaffar S. 2009. Con Petsoglou for referring the case.24:928–32. 5. McLean WH. 10. 2 in this report with surprisingly large hyporeflective lesions described as ranging in size from 5 to 145 m. Orntoft T. Gritz DC.11. hypertonic saline) could also be considered in cases such as this one where exacerbation of symptoms on waking is reported.13. Kinoshita S. Br J Ophthalmol 2000. 1996:1505–52. the diagnosis of Meesmann dystrophy in this case series was subsequently questioned. Surgical interventions typically used for recalcitrant RCE such as manual epithelial debridement. Cornea 2005.11 High magnification in vivo descriptions of Meesmann dystrophy such as can be obtained with the confocal microscope are rare.. Wagoner MD. Cornea 1999. Swensson O. 10. Acta Ophthalmol 2008. Badr IA. prednisolone. 8.18:144–54. Thiel HJ.e. Skotnitsky C.8. Microcyst response to high Dk/t silicone hydrogel contact lenses. Optom Vis Sci 2000. 6. In: Pepose JS.14 The confocal microscopy appearance of Meesmann dystrophy described in the single case series published to date differs significantly from that shown in Fig. Cornea 1999. Smith FJ. Meesmann corneal Optometry and Vision Science.19 Although these abnormal corneas may be more vulnerable to traumatic injuries and infections. Grupcheva CN. 2007.13 Anterior stromal puncture is not recommended in Meesmann dystrophy cases because the extent of the area of the epithelium affected by the disease is large and the process could result in widespread scarring. Schwartz GS. Swensson B. Glasgow BJ.11. and lamellar and penetrating keratoplasty should be considered in severely debilitating cases in the hope of stabilizing the corneal epithelial and associated symptoms. Classification of herpes simplex virus keratitis. Goldberg A. accepted May 26. 2. Vol. A novel arginine substitution mutation in 1A domain and a novel 27 bp insertion mutation in 2B domain of keratin 12 gene associated with Meesmann’s corneal dystrophy.11.21.8 This case was managed with therapeutic contact lenses that allowed her to return to work.14 Interestingly. Seitz B. Jabak M. Munier FL. Liesegang TJ. eds.24 These findings are consistent with the appearance described in ultrastructural studies. 6th ed. The difficulty in correctly diagnosing this dystrophy is evidenced by the range of treatments (i. Hjortdal J. Moore JE. Rochels R. A 40-year-old Danish women reported photophobia so severe that the windows of her family home were permanently masked with black plastic sheets. 13. 4. Chao SC. Cornea 2008. Holden BA. Keay L. Van Rij G. Kanski JJ. Nielsen K.17. Wilhelmus KR. Meesmann A. Moller HU. Tseng SH. Holsclaw DS. Seiler T. Imaging the microstructural abnormalities of meesmann corneal dystrophy by in vivo confocal microscopy. Lisch W. Br J Ophthalmol 2002. Corden LD. Clinical Ophthalmology: A Systematic Approach. Int Ophthalmol 1997.86:729–32. A novel mutation in KRT12 associated with Meesmann’s epithelial corneal dystrophy. McGhee CN. The risk of recurrence with all surgical procedures is high as the corneal stem cells retain the mutated genes and the chances of remaining disease free for longer than 1 month are low. Aldave AJ. 14. Holland EJ.g.2 Although rare. This work was supported by the Australian Government through the Cooperative Research Centre scheme. Uber eine bisher nicht beschribene. Morgan SJ. Mannis MJ. describing hyperreflective cystic lesions of 10 to 50 m. dominant vererbte Dystrophia epithelialis corneae. which complicated the diagnosis and management of the condition. Yoon MK. Coleman CM. ACKNOWLEDGMENTS We thank Dr. The IC3D classification of the corneal dystrophies.23 A previous report seems more consistent with our confocal microscopy investigation. Novel mutations in the helix termination motif of keratin 3 and keratin 12 in 2 Taiwanese families with Meesmann corneal dystrophy. Sweeney DF. Ocular Infection and Immunity.88:752–6.27 (suppl 2): S1–83. 3. Holland GN. Irvine AD. McCarthy JH.8 It is interesting to note that there are reports in the literature of Meesmann dystrophy cases being intolerant to contact lens wear because of epithelial fragility. Jalbert I.16 Individual anatomical variations in the sub-basal nerve plexus and/or limbal stem cells may underpin some of these differences and ongoing examination of such cases with in vivo confocal microscopy may provide further clues. Ber Deutsch Ophthalmol Ges 1938. 12. Klintworth GK. Phenotypic variability in Meesmann’s dystrophy: clinical review of the literature and presentation of a family genetically identical to the original family. Hypertonic agents may help stabilize the diseased epithelium potentially affected by the physiological overnight corneal edema. 9. topical dexamethasone. Wannke B. Margolis TP. St Louis: Mosby.. Thiel HJ.22 Marked vacuolization and dense periodic acid Schiff positive intracytoplasmic inclusions21 were observed in the deeper epithelial layers. by the Institute for Eye Research and by the Contact Lens Society of Australia. Unilateral Meesmann’s dystrophy. No. Chen YT. REFERENCES 1. The use of a topical cycloplegic such as 1% cyclopentolate or 2% homatropine for the relief of symptoms in severely photophobic cases remains a treatment option. excimer laser phototherapeutic keratectomy.84: 527–30. ¨ 7. there are reports of cases being severally handicapped by Meesmann dystrophy. Black GC. Adachi W. 22. Frazer DG. Florakis GJ. McLean WH. Swensson O.au Optometry and Vision Science. Cornea 1998. Corden LD. epithelial dystrophy in a Saudi Arabian family. Imaging the microstructural abnormalities of Meesmann corneal dystrophy by in vivo confocal microscopy.ncbi. Kawasaki S. 17.jalbert@unsw. No. On-line Mendelian Inheritance in Man (OMIM): #122100: Corneal Dystrophy. Coleman CM.128:687–91. Pitts E. Williams VA.gov/entrez/dispomim. Invest Ophthalmol Vis Sci 1996. NSW 2052 Australia e-mail: i. Isolation and chromosomal localization of a cornea-specific human keratin 12 gene and detection of four mutations in Meesmann corneal epithelial dystrophy.16:184–7. MECD. Christophers E. Mutations in cornea-specific keratin K3 or K12 genes cause Meesmann’s corneal dystrophy. Renard G. Am J Ophthalmol 1998.nlm. Knowlton RG. Meesmann’s epithelial dystrophy of the cornea. Baltimore: John Hopkins University. Mayer F. Yamamoto S.83:633–42.125:182–6.edu. McKusick VA. Converse RL. 86.25:868. 1986. Yanoff M. 10. 20. Savoldelli M. Chiesa R. McLean WH. Kao WW. Quantock AJ. Ishizaki M. Shimomura Y. 2009. Moore JE. Kao CW. nih. Irvine AD. Covello SP. Hosotani H. Duffy J. Nat Genet 1997. Swensson B. Hannush S. Legeais JM. Uitto J. Ophthalmology 1998. Available at: http://www.cgi?id 122100. Dighiero P. Vol. Nakamura T. Fine BS. Am J Ophthalmol 1977.E1206 Management of Symptomatic Meesmann Dystrophy—Jalbert and Stapleton Doetschman T. Chiou AG. Cornea 2006. Nishida K. Confocal microscopy of cystic disorders of the corneal epithelium. Slaughter FD. 19. Kinoshita S. Rochels R. Isabelle Jalbert School of Optometry and Vision Science The University of New South Wales Sydney. Dota A. Smith FJ. Accessed July 14. Bron AJ.61:1268–75. Tuft S. Meesmann. 24. McCormick SA. 21. Copeland RL. Am J Ophthalmol 1999. October 2009 . A novel mutation in the helix termination motif of keratin K12 in a US family with Meesmann corneal dystrophy.17:566–70. Recurrent Meesmann’s corneal epithelial dystrophy after penetrating keratoplasty. Am J Hum Genet 1997. Briat B. Smith FJ. Uitto J. Hernandez-Quintela E. 16. Keratin 12-deficient mice have fragile corneal epithelia.105:631–6.37:2572–84. Okada M. Liu CY. 18. Honma Y. 23. Shiraishi A.