CASE REPORT

Corneal melt in lattice corneal dystrophy type IIafter cataract surgery

Miltiadis Papathanassiou, MD, PhD, Vasilios S. Liarakos, MD, Emmanuel Vaikousis, MD,Thrasivoulos Paschalidis, MD, George Agrogiannis, MD, Ioannis Vergados, MD, PhD

We report a patient with lattice corneal dystrophy type II, also known as Meretoja syndrome orfamilial amyloidosis Finnish type, who developed a corneal melt 15 days after uneventful phaco-emulsification. Despite conservative treatment, the corneal melt resulted in perforation. Unevent-ful penetrating keratoplasty was performed, but delayed graft epithelial healing was noticedpostoperatively. Corneal button histopathological evaluation confirmed the initial clinical diagno-sis. To our knowledge, this is the first reported case of corneal melt and perforation in a patientwith lattice corneal dystrophy type II.

J Cataract Refract Surg 2009; 35:185–189 Q 2009 ASCRS and ESCRS

Lattice corneal dystrophy is a congenital hereditarydisease, usually bilateral. Lattice dystrophy type II aswell as type I and type IIIa are inherited as an autoso-mal dominant trait, whereas type III is autosomal re-cessive. Jones and Zimmerman1 first attributed thisdisorder to amyloid degeneration of the stromal colla-gen fibers, with no effect on the corneal endotheliumand Descemet membrane. Randomly scatteredbranching lattice figures evolving within the stromaare pathognomonic for this disease. They are bestseen on retroillumination. In type II, the figures aremore sparse, more delicate, andmore radially orientedthan in type I, where they usually avoid the peripheryand lead to stromal haze that progressively impairsvision.

Symptoms are mild and usually begin in the firstdecades of life in the form of decreased vision or

Submitted: May 20, 2008.Final revision submitted: July 15, 2008.Accepted: July 18, 2008.

From the 2nd Department of Ophthalmology (Papathanassiou,Liarakos, Vergados), Attikon Hospital, and the 1st Department ofPathology (Agrogiannis), School of Medicine, University of Athens,and the Department of Ophthalmology (Vaikousis, Paschalidis), AgPanteleimon General Hospital, Athens, Greece.

No author has a financial or proprietary interest in any material ormethod mentioned.

Corresponding author: Miltiadis Papathanassiou, MD, PhD, 2ndDepartment of Ophthalmology, Attikon University Hospital, 1Rimini Street, 12667, Athens, Greece. E-mail: mpapathanassiou@yahoo.com.

Q 2009 ASCRS and ESCRS

Published by Elsevier Inc.

recurrent epithelial erosions and delayed epithelialhealing, which are attributed to subepithelial stromalaccumulation of amyloid material.2 In type II, the on-set of symptoms is later than in type II and recurrentepithelial erosions are less frequent. Amyloid depositsin the anterior stroma stain with Congo red, as first de-scribed by Klintworth,3 and show characteristic greenbirefringence when viewed with a polarized filter.Staining with thioflavin-T is helpful in further charac-terizing the amyloid material.

Meretoja4 was the first to associate lattice cornealdystrophy with cranial neuropathy, skin changes,and other systemic symptoms forming one hereditaryclinical entity. Lattice corneal dystrophy type II(Meretoja syndrome5) is associated with systemicamyloidosis6 or type IV amyloidotic polyneuropathy.7

Systemicmanifestations include primary systemic amy-loidosis, usually affecting the kidneys,8 heart, liver, orskin; progressive cranial or peripheral amyloidoticpolyneuropathy; and cutis laxa. The other recognizedtypes of lattice dystrophy (types I, III, IIIA, and IV) arenot associated with systemic disease. Mutations ofa different gene cause at least 3 of these entities.9

Other than delayed epithelial healing, reduced cor-neal sensitivity, or recurrent epithelial erosions, noother major complications of this condition havebeen described. We report a case of sterile cornealmelt and perforation after uneventful cataract surgeryin a patient with a diagnosis of Meretoja syndrome.

CASE REPORT

An 81-year-old man presented with reduced visual acuity of20/100 in the right eye and 20/60 in the left eye due to cata-ract formation. Slitlamp examination revealed bilateral

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186 CASE REPORT: MERETOJA SYNDROME

lattice lines in the corneal stroma, which were radially ori-ented and involved primarily the periphery, with relativelyfew in the central region (Figure 1). The observed lattice fig-ures did not seem to obstruct vision in either eye. The condi-tion resembled classic lattice dystrophy (type I) but withfewer amorphic deposits, which were more confined in dis-tribution. Tear-film evaluation showed no significant abnor-mality (break-up time was 8 seconds in the right eye and 10seconds in the left eye and the Schirmer test was 10.0mmand12.0 mm, respectively); however, corneal sensitivity, as-sessed with the Cochet-Bonnet asthesiometer, was lessthan that in patients of the same age.

The patient did not mention a history of ophthalmicdisease, but family history revealedundiagnosed corneal dis-ease in the patient’s father that resulted in decreased visualacuity in both eyes. The patient was under treatment forchronic renal failure due to primary systemic amyloidosis.No cutaneous or mucocutaneous lesions were recorded.Heart and liver functionswere satisfactory, and theneurolog-ical examination was normal. Blood examination revealedincreased serum glucose levels (169 mg/dL), increased se-rum creatinine levels (2.1 mg/dL), increased serum urealevels (115 mg/dL), increased lactose dehydrogenase(292IU/l), and creatine phosphokinase (284IU/l). Clinicaldiagnosis of bilateral lattice corneal dystrophy associatedwith primary systemic amyloidosis, presenting as renal amy-loidosis, led to a diagnosis of Meretoja syndrome.

Uneventful phacoemulsification with intraocular lens(IOL) implantation was performed in the right eye. Surgerywas accomplished through a temporal 2.75 mm clear cornealincision using a modern phacoemulsification machine witha peristaltic pump and a routine stop-and-chop technique.During surgery, the corneal epithelium was protected bya hydroxypropylmethylcellulose coating. Dispersive andcohesive ophthalmic viscosurgical devices were used forcapsulorhexis and IOL implantation, respectively. Postoper-atively, topical ofloxacin 0.3% 4 times a day and dexametha-sone 0.1% 4 times a day, both with preservatives, wereprescribed. Hydromellose preservative-free drops wereadministered every 2 hours.

Figure 1. Slitlamp photograph of lattice lines in the corneal stroma ofthe fellow eye.

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On the first postoperative visit (day 2), mild diffuse epi-thelial staining, together with mild anterior chamber flare,was noticed. Fourteen days later, the patient presentedwith significantly reduced visual acuity in the right eye(best corrected visual acuity, hand motion at 2 ft). He re-ported a history of gradual deterioration of vision in the pre-vious 2 weeks accompanied by mild pain and redness of theeye. There was moderate lid edema and conjunctival hyper-emia. Slitlamp examination revealed an extensive centralcorneal melt (4.0 mm� 5.0 mm) with an overlying epithelialdefect and a small paracentral perforation (1.0 mm �1.5 mm), giving a positive Seidel test (Figure 2). There wasdiffuse corneal edema and total athalamia. Corneal and con-junctival cultures taken for common bacteria and fungi werenegative. In the presence of corneal melt, the patient wasevaluated for collagen vascular disease or vasculitis. Apartfrom the known chronic renal failure due to amyloidosis,the clinical examination did not reveal anything abnormal.

Figure 2. Slitlamp photography of corneal melt and perforation atpresentation.

Figure 3. Slitlamp photograph of delayed epithelial healing afterpenetrating keratoplasty.

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Figure 4. A: Corneal thinning (black arrowheads) near the site of perforation (H&E staining, original magnification �100). Accumulations of sub-epithelial fibrillarmaterial are seen in the nearby anterior stroma (black arrows; H&E staining; originalmagnification�200). B: Congo red stainingof abnormal subepithelialmaterial reveals amyloid deposits (black arrows; H&ECCongo red staining; originalmagnification�200) near themelt(black arrowheads; H&E C Congo red staining; original magnification �100).

Laboratory results (antinuclear antibodies, rheumatoid fac-tor, and antineutrophilic cytoplasmic antibodies p-ANCAand c-ANCA) were also negative.

Cyanoacrylate glue was applied, and the anterior cham-ber was temporarily reformed. Topical ofloxacin anddexamethasone were administered every 2 hours, cyclopen-tolate 1% 3 times a day, and oral systemic steroids, prednis-olone, 60 mg/day. Uneventful therapeutic penetratingkeratoplasty was performed 5 days later. During follow-up, delayed epithelial healing of the graft was noticed (Fig-ure 3) and managed successfully with intense lubricationand application of a bandage therapeutic contact lens.

Histopathological examination of the corneal button re-vealed an irregular cornea with thinning in the center. Thesquamous epithelial layer demonstrated loss of normal ar-chitecture, while there was loss of corneal stroma in the cen-tral region. The surrounding cornea showed scarring withirregular fibroblasts. Sparse cellular infiltrates were alsopresent. There were fusiform deposits beneath Bowmanlayer and at the anterior stroma; these stained pink–redwith hematoxylin and eosin, displacing collagen lamellae(Figures 4 and 5). The fibrillar deposits were congophilicand emitted apple-green birefringence and dichroism

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when viewed under polarized filters. Descemet membranewas unremarkable, and the endothelial cells were intact.These findings were indicative of subepithelial amyloid de-posits, confirming the diagnosis of lattice corneal dystrophy.

DISCUSSION

In this patient, the diagnosis of lattice corneal dystro-phy in both eyes associated with primary systemic amy-loidosis, presenting as renal amyloidosis, led to thediagnosis of Meretoja syndrome. Amyloid depositsin the cornea and the kidneys are sufficient to diagnoseMeretoja syndrome.8 Histopathological examinationof the corneal button confirmed the clinical diagno-sis.10 The ‘‘undiagnosed’’ corneal disease, whichcaused gradual deterioration in the visual acuity (butnot blindness) in the patient’s father, could havebeen lattice dystrophy, which is inherited in the auto-somal dominant way.11 Meretoja syndrome is also re-ferred to as familial amyloidosis, Finnish type (FAF),

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or as gelsolin-related amyloidosis.12 Amyloid depositsare found in the anterior stroma, beneath a normal-ap-pearing Bowman layer, and they often form scar tissueinvading the subepithelial space,13 as in our case.Some investigators suggest that Meretoja syndromecan be diagnosed even retrospectively from cornealbuttons subjected to histopathological study,13

whereas others say the accumulation of gelsolin isnot confined to Meretoja syndrome and therefore isnot pathognomonic; ie, it may be seen in various formsof amyloidosis.14

In a patient with corneal melt, the diagnostic ap-proach should first exclude the possibility of an infec-tion. Patients should also be evaluated for systemicconditions such as rheumatoid arthritis or vasculitissecondary to polyarteritis nodosa or Wegener granu-lomatosis.15,16 These systemic disorders sometimes be-come evident only after the presentation of corneal orscleral melt. Local factors are also important in the dif-ferential diagnosis of corneal melt cases. Severemeibo-mianitis and dry eyes may cause melting. Epithelialbreakdown after direct trauma, as surgical trauma,or even microerosions secondary to dry eyes permitthe influx of inflammatory cytokines in the cornealstroma and the initiation of an inflammatory cascadeleading to corneal melting. Cell-mediatedmechanismsappear to be important in the etiopathogenesis of cor-neal melting. Additionally, stromal gelatinolytic activ-ity and stromal collagenase (matrix metalloprotease-1)production have been proposed to play some role.Subsequently, immunosuppressive and immunomo-difying drugs as well as anticollagenase treatmentsuch as medroxyprogesterone may have a protective

Figure 5. Formalin-fixed paraffin-embedded corneal section fromthe site of the corneal melt. Excessive stromal thinning and loss ofnormal architecture are evident in the central area. Congo red stainssubepithelial and stromal fibrillarmaterial (black asterisks), indicatingamyloid deposits (H&E C Congo red staining, original magnifica-tion �20).

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effect on melt onset and severity.15–19 Subsequent cat-aract surgery in the fellow eye should include the closepostoperative follow-up needed in these patients, aswell as the aggressive management of any postopera-tive inflammation or epithelial defect that may occur.

Our patient was probably predisposed to poor epi-thelialization and corneal wound healing because ofthe lattice corneal dystrophy. Delayed epithelial heal-ing in lattice corneal dystrophy type II has been de-scribed.20,21 Rosenberg et al.22 have shown that thesubbasal nerve density appears reduced in cornealdystrophy type II, which results mainly in mechanicaland, to a lesser extent, thermal sensitivity. Subepithe-lial accumulations of fibrillar amyloid deposits caus-ing distortion of the epithelial contour, together withbasement membrane irregularity and discontinuity re-sulting from underlying amyloid fibrils, lead to an ab-normal corneal surface and obstruction ofreepithelialization. Mutation of the gelsolin gene anddisturbed function of the produced protein mightalso interfere with the attachment of epithelial cellsto the underlying stroma and thereby lead to sponta-neous erosions.

Lattice corneal dystrophy type II also causes a pro-gressive loss of corneal sensory nerves, resulting in im-pairment of corneal sensory modalities.22 Tearsecretion is impaired after corneal sensory denerva-tion.23 Because corneal nerves are known to play animportant role in maintaining corneal epithelial integ-rity24 and tear secretion,23 the reduction in the numberof subbasal nerves22 most probably accounts for thedevelopment of epithelial erosions. Subsequently,nonhealing epithelial defects are anticipated in thesepatient. Some mild epithelial defect induced duringcataract surgery could have been enough to producea nonhealing epithelial erosion. Reduced corneal sen-sitivity and subsequent dry eyes could damage epithe-lial integrity and produce a persistent epithelial defect,which could progress to corneal melt, assisted by theusual postoperative inflammation.

In the literature, postoperative corneal melting hasbeen associated with the topical use of nonsteroid anti-inflammatory drugs (NSAIDs). Diclofenac sodium0.1% is thought to induce aberrant (excessive or inap-propriate) matrix metalloproteinase expression in thecornea, which is associated with corneal keratolysis.25

Central corneal melting has recently been associatedwith the use of modern NSAIDs, especially nepafe-nac26,27 andbromfenac,28 after routine cataract surgery.However, no NSAID was prescribed for our patient.

To summarize, we think a combination of local fac-tors with the background of systemic amyloidosis andlattice corneal dystrophy resulted in the unusual post-operative corneal melt in our patient. The coexistenceof postoperative epithelial breakdown, mild dry

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eyes, and slightly more than usual postoperative in-flammation with overexpression of cytokines, alongwith the background of reduced corneal sensitivityand difficult epithelial healing characterizing the lat-tice dystrophy, resulted in an aggravating responseand subsequent corneal melt. The gap in the postoper-ative follow-up between day 2 and day 14 was enoughto permit the full clinical picture to develop. Close fol-low-up is indicated in such cases. Intense lubrication,postoperative use of preservative-free drops, bandagetherapeutic contact lenses, and even temporary tarsor-raphy or botulinum toxin-induced upper lid ptosisshould be in the armamentarium for the postoperativecare of lattice corneal dystrophy patients. Intensivecontrol of any postoperative inflammation is equallyimportant in their management.

To our knowledge, this is the first report of cornealmelt and subsequent perforation in a patient with lat-tice corneal dystrophy type II after uneventful phaco-emulsification. Cataract surgery in these patientsshould alarm clinicians and prompt close postopera-tive follow-up and intensive treatment of any cornealepithelial defect as a potential neurotrophic ulcer.

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