589

Corneal stromal infiltrates inpatients with recurrent erosionsHelena M. Tabery

Lund University, Department of Ophthalmology, Malmo University Hospital,Malmo, Sweden

ABSTRACT.Purpose: To report six patients with recurrent erosions and apparently sterileanterior stromal infiltrates.Method: The patients were examined in the slit lamp.Results: The infiltrates resolved slowly in one patient treated only with anti-biotics, and more rapidly with the addition of topical steroid treatment in five.In one patient, shortly after the resolution, a new infiltrate appeared in a differ-ent site. Another patient suffered a year later a new, but uncomplicated episodeof recurrent erosion. Three patients developed during the course of the diseasea late phenomenon of nummular superficial opacities which disappeared spon-taneously. 5/6 patients had anterior basement membrane dystrophy.Conclusions: The clinical features are suggestive of a non-infectious process.The striking similarities in the patients’ history and clinical picture imply acausative relationship with recurrent erosions. The inflammatory reaction, poss-ibly occurring only in predisposed individuals, seems to be provoked by epithelialbreakdowns. The nature of the stimulus is uncertain, but it might be of epithelialorigin.

Key words: cornea – recurrent erosion – basement membrane dystrophy – immunity.

Acta Ophthalmol. Scand. 1998: 76: 589–592Copyright c Acta Ophthalmol Scand 1998. ISSN 1395-3907

Recurrent corneal epithelial erosion,with or without antecedent

trauma, is a common disease occurringin patients with epithelial basementmembrane dystrophy (BMD), and, morerarely, in apparently normal corneae.The regular features of BMD consist ofsuperficial corneal changes, partlylocated in the epithelium (cysts, ero-sions) and partly at the level of the base-ment membrane (greyish membranesand fingerprint lines). The developmentof anterior stromal infiltrates seems tobe a very rare complication, so far re-ported in 5 (Shoch et al. 1985), 1(Jaros & DeLuise 1986), 1 (Hykin et al.1994), 5 (Luchs et al. 1995) and 11 (Ion-ides et al. 1997) patients. The present re-port concerns six patients with similarinfiltrates. A detailed description of thecourse of their disease is presented.

Case ReportsCase 1

A 45-year-old man with basement mem-brane dystrophy in both eyes and recur-rent erosions in the right eye (followingan accident in August, 1986) presentedon March 25, 1989, with a new, large,spontaneous central epithelial erosion.He was initially treated with chloram-phenicol ointment. Four days later theeye showed a centrally located, whitish,anterior stromal infiltrate with ulceratedsurface, Descemet’s membrane folds, andanterior uveitis. Neither addition ofcycloplegics nor soft contact lens im-proved the condition which remained un-changed during the following four days.Corneal scrapings were negative for bac-teria. On April 2, treatment with dexa-methasone 0.1% eye drops twice daily

was added, and the inflammatory reac-tion started to subside. During the fol-lowing days the contact lens was discon-tinued and dexamethasone treatment wasincreased to 3 times daily. On April 13the eye was quiet. Dexamethasone wasdiscontinued on April 18 because of un-certainty as to the nature of several satel-lite lesions, appearing as small superficialstromal nummular opacities with intactor slightly defective overlying epithelium.Within two days the surface became in-tact and the small opacities assumed anappearance reminiscent of subepithelialinfiltrates in adenovirus infections; thesite of the initial infiltrate remained quiet.On June 6 the small opacities were gone.The infiltrate left a central stromal scar,and the final corrected vision was 10/20.One year later the patient suffered a newerosion located below the centre (inferiorto the scar) which healed rapidly andwithout complications. In January, 1996,when last seen, he reported no furtherepisodes.

The patient was in good general healthexcept for an episode of asthmatic symp-toms which resolved after change ofwork, and a transient oblique superiorpalsy in the right eye in 1992.

Case 2

A 48-year-old woman with recurrent ero-sion in her left eye since 1991, and a base-ment membrane dystrophy in both eyes,presented on July 26, 1993, with a cen-trally located, whitish, anterior stromalinfiltrate, corneal edema and a severe an-terior uveitis. There was no antecedenttrauma and the duration of symptomswas four days. Treatment with antibioticointment (neomycine-bacitracine) andcycloplegics had no effect; during the fol-lowing four days the condition remainedunchanged. Conjunctival smears revealedno bacteria. Addition to the regimen of

590

dexamethasone 0.1% eye drops twicedaily had an immediate effect on the in-flammatory reaction, and the infiltrate re-solved, leaving a superficial stromal scar.When last seen in September, 1994, shehad no symptoms and her unaided visionwas 20/20.

The patient had a history of recurrentepiscleritis and carpal tunnel syndrome.

Case 3

A 47-year-old woman with spontaneousrecurrent erosion in her right eye pre-sented on April 4, 1994, with a new ero-sion, localised below the centre. The lefteye showed fingerprint lines. She wastreated with chloramphenicol ointment.24 hours later the erosion was unchangedand at its lower edge a whitish anteriorstromal infiltrate was present. Within afurther 24 hours a generalised epithelialand stromal edema developed; the infil-trate was unchanged. The condition nei-ther worsened nor improved during thefollowing six days. Dexamethasone 0.1%eye drops twice daily were added to theregimen, and within five days the eye be-came quiet. The resulting stromal scardid not influence the visual acuity. Con-junctiva smears revealed staphylococcusaureus.

The patient’s history revealed episcler-itis in the right eye in 1976, nontraumaticconjunctival ulceration in the left eye in1983, macular edema due to vascularanomaly of unknown origin in 1992,back pain treated elsewhere, and penicil-lin allergy.

Case 4

A 46-year-old woman with basementmembrane dystrophy in both eyes diag-nosed in 1989 presented on May 12, 1995,with a spontaneous central erosion and amild uveitis in her left (amblyopic) eye.She was treated with chloramphenicolointment and cycloplegics. Four dayslater the erosion was healed, but the epi-thelium was edematous in an area sur-rounding a round, whitish, nonulceratedanterior stromal infiltrate located at thelower edge of the original erosion. Shewas treated with neomycine-bacitracineointment. Resolution of the infiltrate oc-curred within three weeks. Four weeksafter the onset the eye showed a super-ficial stromal scar and superficial num-mular opacities resembling sequelae of vi-rus keratitis. These opacities disappearedspontaneously.

The patient was in good generalhealth.

Case 5

A 51-year-old man with spontaneous re-current erosions in the right eye sinceJuly, 1994, presented on August 29, 1995,with an irritated and painful right eye,showing below the centre an elevated, butintact epithelium; basement membranedystrophy was present in the fellow eye.He was initially treated with chloram-phenicol ointment and cycloplegics. Twodays later the cornea showed generalisedepithelial edema and a large epithelialerosion below the centre, and sodiumchloride ointment 5% was added to theregimen. Four days later the epithelialedema had resolved and the erosion washealed except at its lower edge, whichshowed a whitish anterior stromal infil-trate; stromal edema and anterior uveitiswere also present, and in the central partof the cornea very discrete greyish flecks,located approximately at the level ofBowman’s layer, were visible. Antibiotictreatment (chloramphenicol, neomycine-bacitracine ointment) didn’t improve thecondition during the following two days.Microbiologic work-up including scrap-ings of the infiltrate and direct inocu-lation onto culture media revealed nopathogen. Following treatment withdexamethasone 0.1% eye drops twicedaily the inflammatory reaction startedto subside and the infiltrate to resolve.The drops were slowly tapered to everyother day, and discontinued on October11. On that occasion the eye was quiet;the central cornea showed small, super-ficial greyish opacities, an anteriorstromal scar below the center, and nasallyfrom it two small areas with disturbedand elevated epithelium. Approximatelyin the same location, when again seen 9days later because of augmenting irri-tation, a new whitish infiltrate had de-veloped (Fig. 1a). A second microbiologi-cal work-up also failed to reveal patho-gens. The eye was treated withdexamethasone 3 times daily and the in-flammatory reaction subsided. The cen-tral cornea developed superficial stromalnummular opacities (reminding of thosefollowing adenovirus infections, Fig. 1c).Steroids were slowly tapered, and whenlast seen, in June, 1996, no steroids hadbeen used for 2 months. The eye wasquiet, showed two superficial stromalscars (Fig. 1b), and in the central corneavery discrete nummular opacities werestill discernible; the best corrected visionwas 20/20.

The patient was subjectively healthy;

Fig. 1. Corneal infiltrates in recurrent erosion/basal membrane dystrophy (case 5).A. The whitish anterior stromal infiltrate has alobulated appearance suggestive of confluenceof at least two lesions. Two areas located ap-proximately in the center of each are morestrongly light reflecting (arrows). Bar 500 mm.B. The infiltrate resulted in a superficial stromascar (arrow; arrowhead indicates the right edgeof the illuminated strip of fluorescein stainedtear film).C. Late phenomenon of superficial nummularopacities resembling infiltrates due to aden-ovirus infections. Bar 250 mm.

low Schirmer 1 test values were suggestiveof a possible keratoconjunctivitis sicca.

Case 6

A 40-year-old man presented in August,1996, with a corneal erosion after beingstruck in his left eye by a leaf. Threemonths later he suffered a spontaneouserosion in the same eye. At presentation,the eye showed a subcentrally located ero-sion; the duration of symptoms was twodays. The fellow eye appeared normal.He was treated with chloramphenicolointment and patching. Within two daystwo rounded, whitish, and partly conflu-ent superficial stromal infiltrates de-veloped in the same location. He wastreated with neomycine-bacitracine oint-ment, but the infiltrates remained un-changed over the following two days.With prednisolonacetate eye drops 0.5%twice daily added to the regimen, the in-filtrates started to resolve. The resultingsuperficial stromal scar didn’t influencethe visual acuity. Conjunctival smears re-

591

vealed staphylococcus aureus, sensitive tothe used antibiotics.

The patient had a chronic blepharitis;he gave a history of recurrent bouts of se-vere urticaria and a family history of al-lergy.

DiscussionFive of the present patients had in com-mon a history of uncomplicated recur-rent erosions and all six, in connectionwith a spontaneous erosion, a sudden de-velopment of an anterior stromal infil-trate located in the area of the defectiveepithelium. The dimensions of this rela-tively small infiltrate (about 1–1,5 mm indiameter, rounded or lobulated and sug-gestive of confluence of several lesions)seemed to be rapidly established. Duringthe following days, the infiltrate neithershowed progress nor improved with anti-biotics. Secondary to the accumulated ex-perience, resolution of such infiltrates oc-curred within a couple of days (Shoch etal. 1985) or about 2–3 weeks (case 4). Inmore severe cases, addition of topicalsteroids rapidly alleviated the symptomsand seemed to have shortened the diseaseperiod (cases 1–3 and 5–6).

Experience with possible recurrencesof the infiltrates is so far limited to threepatients: one patient with rosacea (Ionid-es et al. 1997) and two of the present ones(cases 1 and 5). In case 5, it is notablethat the relapse occurred shortly after (avery cautious) steroid withdrawal, but ina different site. This seems to indicatethat the inciting stimulus had been locallyeliminated during the healing process,and that the relapse was due to a newattack In case 1, a new erosion occurringa year later remained uncomplicated.

The superficial location of the infil-trates suggests that the stimulus precipit-ating the inflammatory response reachesthe stroma via the anterior corneal layers.In connection with a defective epithelialbarrier, such infiltrates are primarily sus-pected to be of microbial origin. In onestudy (Luchs et al. 1995), bacteria wereisolated in 4/5 cases. In another study(Ionides et al. 1997), cultures performedin all 11 patients in samples obtainedfrom the lid margins, conjunctiva and theinfiltrates revealed bacteria in 2 of thecorneal, and in 3 of the lid samples. Inthat study, it was noted that the severityof the clinical signs didn’t correlate withthe culture results, and the same was ob-served in the present one in which staphy-

lococcus aureus was isolated from con-junctival swabs in 2 patients (cases 3 and6). The absence of both prophylactic andtherapeutic effects of broad-spectrumantibiotics, the stationary nature of theinfiltrates, and the favourable effect oftopical steroids make live replicatingmicroorganisms an improbable cause.

Hence, these infiltrates seem to be ster-ile. Presumed sterile infiltrates are knownto develop in a variety of conditions, forexample in connection with staphylococ-cal blepharitis, as sequelae of virus infec-tions, in contact lens wear, or forming apart of the disease spectrum in systemicimmunologically mediated diseases suchas rheumatoid diseases and systemic vas-culitis, in Mooren’s ulcer, Cogan’s syn-drome. In many of these diseases, auto-immune origin has been suspected, andcirculating antibodies to the corneal epi-thelium have been found (Kruit et al.1986; John et al. 1992; Majoor et al.1992; Albers et al. 1992).

Of particular interest to the presentmatter is a report (Mondino et al. 1977) ona patient with a severe disease. The devel-opment of sterile stromal infiltrates waspreceded by spontaneous recurrent cor-neal and conjunctival (cf. case 3) erosions,the infiltrates were recurrent (cf. case 5 andIonides et al. 1997), occasionally multiple(cf. case 6 and Jaros & DeLuise 1986), andeventually involving both eyes. Extensiveimmunological evaluation revealed tissue-fixed antibodies and complement in thepatient’s own conjunctival epithelium, andof circulating antibodies to normal cor-neal and conjunctival epithelium. The pa-tient had a history of allergy, but no mani-fest systemic disease. Immunological sus-ceptibility was suspected because ofseveral immunological test abnormalitiesfound both in the patient and her immedi-ate family.

The clinical similarities between thatpatient and the hitherto reported patientswith recurrent erosions/BMD are sugges-tive of various degrees of severity of thesame disorder in which epithelial break-downs seem to play an important role intriggering the inflammatory reaction (cf.Shoch et al. 1985). The late phenomenonof small superficial opacities, observed inthree of the present patients in additionto the infiltrates, possibly representabortive reactions to the same stimulus.The nature of this stimulus remains un-certain. It is, however, possible that itoriginates in the epithelium itself, andthat the corneal response represents amanifestation of a systemic immunologic

disease. Of the six present patients, one(case 4) was subjectively healthy, in one(case 1) the history was inconclusive, one(case 5) had indications of keratocon-junctivitis sicca often connected withautoimmune diseases, and three (cases 2,3 , 6) a variety of previous disease mani-festations indicating an abnormal im-mune response. Yet, even if perhaps con-cerning only individuals with propensityto systemic immunologic diseases, therarity of the development of apparentlysterile corneal infiltrates in recurrent ero-sions/BMD remains an enigma sinceboth conditions are common.

The suspicion of presumably sterile in-filtrates in recurrent erosions/basementmembrane dystrophy is facilitated by thefairly typical clinical picture. But, how-ever typical, there are no reliable clinicalsigns excluding the presence of potentialpathogens and there is a need for pre-caution. Topical treatment with broad-spectrum antibiotics is a prerequisite forthe safe use of topical steroids.

AcknowledgementThis study was supported by a grant from Her-man Jarnhardts Stiftelse.

ReferencesAlbers FWJ, Majoor MHJM & Van der Gaag

R (1992): Corneal autoimmunity in a pa-tient with relapsing polychondritis. EurArch Otorhinolaryngol 249: 296–299.

Hykin PG, Foss AE, Pavesio C & Dart KG(1994): The natural history and manage-ment of recurrent corneal erosion: a pros-pective randomised trial. Eye 8: 35–40.

Ionides ACV, Tuft SJ,Ferguson VMG, Mathe-son MM & Hykin PG (1997): Corneal infil-tration after recurrent corneal epithelial ero-sion. Br J Ophthalmol 81: 537–540.

Jaros PA & DeLuise VP (1986): Stromal kera-titis with anterior membrane dystrophy. AnnOphthalmol 18: 283–284.

John SL, Morgan K, Tullo AB & Holt PJL(1992): Corneal autoimmunity in patientswith peripheral ulcerative keratitis (PUK) inassociation with rheumatoid arthritis andWegener’s granulomatosis. Eye 6: 630–636.

Kruit PJ, Van der Gaag R, Broersma L &Kijlstra A (1986): Autoimmunity againstcorneal antigens. I. isolation of a soluble 54Kd corneal epithelium antigen. Curr EyeRes 5/4: 313–320.

Luchs JI, D’Aversa G & Udell IJ (1995): Ul-cerative keratitis associated with spon-taneous corneal erosions. Invest OphthalmolVis Sci (Suppl) 36: S40.

Majoor MHJM, Albers FWJ, Van der GaagR,Gmelig-Meyling F & Huizing EH (1992):

592

Corneal autoimmunity in Cogan’s syn-drome? Ann Otol Rhinol Laryngol 101:679–684.

Mondino BJ, Brown SI, Rabin BS & LempMA (1977): Autoimmune phenomena of theconjunctiva and cornea. Arch Ophthalmol95: 468–473.

Shoch DE, Stock EL & Schwartz AE (1985):Stromal keratitis complicating anteriormembrane dystrophy. Am J Ophthalmol100: 199–201.

Received on October 17th, 1997.Accepted on January 21st, 1998.

Corresponding author:

Helena M. TaberyLund UniversityDepartment of OphthalmologyMalmo University Hospital,S-20502 Malmo, Sweden