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Multiple parallel-line endotheliitis: case report and literature review of an emerging entity

      Although rare in the nontransplant setting, several forms of corneal endotheliitis have been described.
      • Suzuki T.
      • Ohashi Y.
      Corneal endotheliitis.
      Viral replication (HSV, VZV, CMZ, and mumps) within the endothelium is a proposed etiology although response to antivirals and topical corticosteroids has been variable.
      • Holland E.J.
      • Schwartz G.S.
      Classification of herpes simplex virus keratitis.
      • Liesegang T.J.
      Classification of herpes simplex virus keratitis and anterior uveitis.
      • Koizumi N.
      • Suzuki T.
      • Uno T.
      • et al.
      Cytomegalovirus as an etiologic factor in corneal endotheliitis.
      • Chee S.-P.
      • Bacsal K.
      • Jap A.
      • et al.
      Corneal endotheliitis associated with evidence of cytomegalovirus infection.
      • Shen Y.-C.
      • Wang C.-Y.
      • Chen Y.-C.
      • Lee Y.-F.
      Progressive herpetic linear endotheliitis.
      • Maudgal P.C.
      • Missotten L.
      • De Clercq E.
      • Descamps J.
      Varicella-zoster virus in the human corneal endothelium: a case report.
      • Singh K.
      • Sodhi P.K.
      Mumps-induced corneal endotheliitis.
      Multiple parallel-line endotheliitis (MPLE) is a rare form of endothelial inflammation characterized by horizontal lines of endothelial dots, stromal edema, and minimal anterior chamber reaction.
      • Oxley L.A.
      • Carrim Z.I.
      Multiple parallel-line endotheliitis—a form of herpes simplex keratitis?.
      • Hori Y.
      • Maeda N.
      • Kosaki R.
      • Inoue T.
      • Tano Y.
      Three cases of idiopathic “multiple-parallel-line” endotheliitis.
      • Le Piane S.
      • Hillenaar T.
      • Remeijer L.
      Self-limiting corneal edema with multiple parallel lines on the endothelium (SCEMPLE).
      We present a case of MPLE and discuss the current literature on this emerging clinical entity.
      A 56-year-old female presented with acute painless vision loss of the right eye noted when waking from sleep. She had no history of trauma, flashes, floaters, curtain defects, redness, epiphora, or discharge. The left eye was unaffected. She had a 3-day history of oral vesicular lesions and a recent upper respiratory tract infection. There was no ocular history and no ocular medication use. Medical history was significant for recurrent herpes simplex of the mouth, diabetes mellitus, hypercholesterolemia, gastroesophageal reflux, obstructive sleep apnea, overactive bladder, and post-traumatic stress disorder. Systemic medication had not changed within the past 12 months and included metformin, rosuvastatin, esomeprazole, tramadol, quetiapine, duloxetine, pregabalin, mirabegron, and lorazepam. The patient used a CPAP machine intermittently but not on the night preceding presentation. She did not recall sleeping with her hand against her face.
      Best corrected visual acuity was 20/60 in the right eye and 20/30-1 in the left eye. Intraocular pressures were 18 and 19 mm Hg, respectively. Pupils, visual fields, and ocular motility were unremarkable. Ishihara colour testing was symmetric (10/14). Floppy eyelids were noted.
      Slit-lamp examination demonstrated mild inferior superficial punctate keratopathy. Evenly spaced horizontal dotted lines along the corneal endothelium were seen on the right in addition to mild stromal edema (Fig. 1). These lines were unchanged on indentation. The anterior chamber was deep and quiet bilaterally on presentation. The left cornea was clear and the remainder of the dilated ocular examination was unremarkable.
      Fig. 1
      Fig. 1Corneal changes seen on the right eye of a 54-year-old female presenting with acute painless decrease in vision demonstrating multiple dots arranged in horizontal parallel lines (A). The extent of these lines, from limbus to limbus, is highlighted on retroillumination (B), while a slit-beam localizes the changes to the endothelium (C).
      Central corneal thickness of 622 μm on the right and 572 μm on the left was measured. There was a decreased endothelial cell count on the right (2545 cell/mm2) compared to the left eye (2941 cells/mm2). Endothelial pleomorphism, spot-like holes, and polygonal deposits arranged in linear configurations were seen on confocal microscopy (Fig. 2). Corneal topography was negative for evidence of astigmatism and keratoconus, OCT of the anterior segment and macula were noncontributory (central macular thickness of 247 μm right and 248 μm left).
      Fig. 2
      Fig. 2Confocal microscopy images of corneal endothelium from the right eye (A) and the left eye (B) of the described patient. The parallel lines seen by slit-lamp biomicroscopy correspond to areas of pleomorphism, spot-like holes, and polygonal deposits arranged in linear configurations, shown in (A). The total endothelial cell count in the right eye was 2545/mm2, and 2941/mm2 in the left eye. A regular pattern of polygonal cells was seen on the left side (B).
      An aqueous sample from an anterior chamber paracentesis 4 days after presentation was submitted for polymerase chain reaction (PCR) testing before therapy. Findings of the PCR analysis for HSV 1 and 2, VZV, and CMV were negative.
      Over the initial 4-day period without treatment, improvement in stromal edema and a decrease in endothelial dots were noted. Treatment with prednisolone acetate 1% and gatifloxacin 0.3% drops QID was initiated after the paracentesis. Within 4 days the endothelial lines had disappeared. Treatment with prednisolone was tapered, and 15 days after presentation, the findings had resolved.
      Endotheliitis has been classified into 4 forms on the basis of keratic precipitate and stromal edema distribution: linear, sectoral, disciform, and diffuse.
      • Holland E.J.
      • Schwartz G.S.
      Classification of herpes simplex virus keratitis.
      Linear endotheliitis, which has been linked to HSV type 1 and CMV, is located peripherally with a single line of keratic precipitates demarcating the boundary of the process. Unlike linear endotheliitis, MPLE demonstrates multiple parallel lines arranged horizontally across the endothelium. To our knowledge, this case represents the 10th in the published English literature. There is no association with the direction of aqueous flow, corneal innervation, or other intraocular structures, and this patient had no identified history of mechanical trauma or pressure to the eye. As with linear endotheliitis, viral replication (particularly HSV) within endothelial cells has been implicated on the basis of positive blood serology in MPLE.
      • Oxley L.A.
      • Carrim Z.I.
      Multiple parallel-line endotheliitis—a form of herpes simplex keratitis?.
      On the contrary, Le Piane et al. observed an absence of HSV-related confocal microscopy findings in a series of MPLE cases.
      • Le Piane S.
      • Hillenaar T.
      • Remeijer L.
      Self-limiting corneal edema with multiple parallel lines on the endothelium (SCEMPLE).
      In another series,
      • Hori Y.
      • Maeda N.
      • Kosaki R.
      • Inoue T.
      • Tano Y.
      Three cases of idiopathic “multiple-parallel-line” endotheliitis.
      a recurrent MPLE affecting both eyes was documented.
      The current patient has a history of assumed recurrent oral HSV with an eruption 3 days before onset of visual symptoms. An aqueous humour PCR assay for HSV was negative. However, this assay is not validated for use on aqueous humour samples. Although high sensitivities are reported using this method in facial and genital specimens, a viral load of 200 copies/mL is required for positivity.
      • Lang A.L.S.
      • Roberts C.
      • Mazzulli T.
      • Hatchette T.F.
      • LeBlanc J.J.
      Detection and differentiation of herpes simplex viruses by use of the viper platform: advantages, limitations, and concerns.
      Lower level HSV activity as might be present within the anterior chamber may be undetected. Serological testing for HSV is of limited value in the setting of active facial vesicles as this would mask evidence of intraocular viral activation. Recurrences of MPLE in this patient will be scrutinized for association with other ocular and nonocular HSV activity. PCR testing for VZV and CMV was also negative.
      Despite the temporal relationship between oral lesions and the ocular findings, HSV was not clearly causative in this patient, and a conservative approach with frequent reassessment was employed. Of note, she had a longstanding history of oral vesicular eruptions with no history of prior ocular symptoms. Spontaneous improvement in the absence of treatment was observed within days. In cases of high clinical suspicion, however, empiric treatment with systemic antiviral therapy may be warranted as treatment is well tolerated and may attenuate the course of this process.
      Partial resolution of findings was observed before initiation of treatment. Initiation of topical steroid therapy caused no striking change in the clinical course. Given that complete resolution of MPLE has been observed in the absence of therapy,
      • Le Piane S.
      • Hillenaar T.
      • Remeijer L.
      Self-limiting corneal edema with multiple parallel lines on the endothelium (SCEMPLE).
      the role played by topical steroids in this case may be limited.
      MPLE is a rare form of endotheliitis resulting in transient, usually unilateral, painless decrease in vision with characteristic findings on examination. The differential diagnosis includes other patterns of endotheliitis, posterior polymorphous corneal dystrophy, mechanical trauma, and rupture of Descemet’s membrane. Several questions remain regarding the cause and pathophysiology of MPLE, particularly with respect to the role of HSV. Complete resolution of manifestations has been well documented, even in the absence of therapy.

      Disclosure

      The authors have no proprietary or commercial interest in any materials discussed in this article.

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