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Superior limbic keratoconjunctivitis following ptosis repair

Published:February 03, 2022DOI:https://doi.org/10.1016/j.jcjo.2022.01.012
      Superior limbic keratoconjunctivitis (SLK) is an inflammatory condition of the superior bulbar conjunctiva, tarsal conjunctiva, and upper cornea of unknown etiology. The pathogenesis of SLK is unclear, although it has been linked to mechanical microtrauma, deficiencies in tear film quality, and immunologic dysregulation.
      • Cher I.
      Superior limbic keratoconjunctivitis: multifactorial mechanical pathogenesis.
      SLK usually presents with irritation, foreign-body sensation, grittiness, burning sensation, and photophobia. Clinically, SLK is characterized by marked inflammation of the tarsal and bulbar conjunctivae of the upper lid, fine punctate fluorescein staining of the superior corneal limbus and adjacent conjunctiva, and a proliferation of superior limbic epithelial cells.
      • Theodore FH
      • Ferry AP.
      Superior limbic keratoconjunctivitis: clinical and pathological correlations.
      Filaments also may be seen at the superior limbus or upper cornea.
      Ptosis repair is one of the most common eyelid procedures performed by ophthalmologists and may be associated with SLK. We present the first five reported cases of SLK that occurred following anterior ptosis repair.
      This retrospective case series involved a chart review of patients who developed SLK following ptosis repair by 3 surgeons (C.S., A.W., and D.S.) from January 2010 to September 2019. Patients with preexisting thyroid disease, dry eyes syndrome, and Sjögren syndrome were excluded. Patient demographic profile, surgical approach used, clinical presentation, and details of the medical and surgical management were studied. The data were maintained using Microsoft Excel (Microsoft Inc, Redmond, Wash.). The study was approved by the Central Adelaide Local Health Network Ethics Committee and adhered to the principles of the Declaration of Helsinki.
      Five patients developed SLK following ptosis repair. The anterior levator advancement approach was used in all patients. A single 6.0 Vicryl suture was placed through partial thickness of the tarsus in the upper third of the tarsus, and the levator was advanced and resected as necessary. None of the patients had postoperative lid retraction, lagophthalmos, or loss of lid–globe apposition following the ptosis repair. All patients were female. The right eye was involved in 2 patients and the left eye in 3 patients. The mean age was 67 ± 7.3 years (range, 55–77 years).
      Preoperatively, none of the patients had evidence of SLK. Following ptosis repair, the patients presented with symptoms of irritation, foreign-body sensation, red eye, grittiness, and heavy upper lids. The mean time interval from the surgery to the diagnosis of SLK was 7.8 ± 4 weeks (range, 3–13 weeks). Examination findings were consistent with SLK (Table 1). These include superior bulbar conjunctival and limbal staining (Fig. 1A, B), superior bulbar conjunctival hyperemia, and superior limbus hypertrophy (Fig. 1C) and staining of the tarsal conjunctiva (Fig. 1D).
      Table 1Clinical profile of patients with SLK following ptosis repair
      No.Age (sex)SidePreoperative diagnosis of SLKPtosis approachOnset of symptoms following surgery (wk)SymptomsSignsMedical managementSurgerySymptoms resolution (treatment modality)
      163 (F)LNAnterior levator advancement4Irritation, lid swelling and rednessSuperior bulbar conjunctival and limbal staining, superior palpebral conjunctival reaction, superior limbal hypertrophy, PEEsLubricants, vitamin A, antibiotic, steroid, BCLNoMedical
      275 (F)LNAnterior levator advancement7Irritation, foreign-body sensation, red eyeSuperior bulbar conjunctival hyperemia and staining, superior limbal staining and hypertrophy, Schirmer I <5 mm, CCLubricants, antibiotic, steroid, rebamipide, punctal plugYes (conjunctivoplasty)Surgical
      355 (F)RNAnterior levator advancement13Grittiness, foreign-body sensation, red eyeSuperior bulbar conjunctival hyperemia and staining, superior limbal staining, CC, lid wiper epitheliopathyAntibiotic, steroid, rebamipideNoMedical
      467 (F)LNAnterior levator advancement3Pain, photophobia, burning sensation, grittinessSuperior bulbar conjunctival hyperemia and staining, superior limbal staining, Schirmer I 4 mm, CC, lid wiper epitheliopathyLubricants, antibiotic, steroid, rebamipide, diquafosol sodium, punctal plug, BCLNoMedical
      577 (F)RNAnterior levator advancement12Discomfort, irritation, heavy upper lidsCorrugated upper conjunctival staining, fine upper conjunctivae papillae, CC, blepharospasm, mild ptosisLubricants, punctal plug, BCLYes (conjunctival excision with amnion patch graft)Surgical
      SLK = superior limbic keratoconjunctivitis; PEEs = punctate epithelial erosions; BCL = bandage contact lens; CC = conjunctivochalasis
      Fig 1
      Fig. 1Clinical photographs showing the superior limbic keratoconjunctivitis signs, including superior bulbar conjunctival and superior limbal staining with fluorescein 2% under blue light (A) and Lissamine green (B); superior bulbar conjunctival hyperemia and superior limbus hypertrophy (C); staining of the tarsal conjunctiva with Lissamine green (D).
      All patients were initially trialled with medical management. Three patients (60%) required the use of a bandage contact lens. A punctal plug also was tried in 3 patients (60%). Two patients (40%) required surgical management to address the SLK, which consisted of conjunctivoplasty in case 2 and conjunctival excision with amnion patch graft in case 5.
      Ptosis repair is one of the more common eyelid procedures performed by ophthalmologists. Our case series suggests an association with SLK. None of the patients in the present series had a previous diagnosis of SLK. All patients had normal anterior-segment examinations prior to surgery. Our surgeons routinely checked for signs of SLK preoperatively. Postoperatively, the diagnosis of SLK is often delayed and may be confounded by inflammation in the early postoperative setting. In our series, the diagnosis of SLK was made a number of weeks after surgery to reduce this risk.
      The pathogenesis of SLK is unclear, although it has been linked to mechanical microtrauma, deficiencies in tear film quality, and immunologic dysregulation. Clinically, the mechanical theory for SLK has been associated with scarring of the superior tarsal conjunctiva
      • Raber IM.
      Superior limbic keratoconjunctivitis in association with scarring of the superior tarsal conjunctiva.
      and upper eyelid blepharoplasty surgery.
      • Sheu MC
      • Schoenfield L
      • Jeng BH.
      Development of superior limbic keratoconjunctivitis after upper eyelid blepharoplasty surgery: support for the mechanical theory of its pathogenesis.
      This theory is also favoured in our case series. The mechanical theory proposes that SLK results from microtrauma between the opposing tarsal and bulbar conjunctivae, conjunctival stroma, and sclera.
      • Cher I.
      Superior limbic keratoconjunctivitis: multifactorial mechanical pathogenesis.
      Microtrauma can be triggered by perturbances in either the interface load between the bulbar and tarsal conjunctivae (e.g., exophthalmos, blepharospasm, contact lens wear), lid dynamics (e.g., blink rate), surface qualities (e.g., keratinization, limbal roll), and tear film deficiency.
      • Cher I.
      Superior limbic keratoconjunctivitis: multifactorial mechanical pathogenesis.
      Ptosis repair may cause conjunctival irritation and alter the lid–globe dynamics, leading to the development of SLK. Surgical treatment of conjunctivochalasis has been very effective in eyes otherwise unresponsive to medical therapies.
      • Yokoi N
      • Komuro A
      • Maruyama K
      • Tsuzuki M
      • Miyajima S
      • Kinoshita S.
      New surgical treatment for superior limbic keratoconjunctivitis and its association with conjunctivochalasis.
      In this series, conjunctivochalasis was seen in 4 patients, requiring surgery in 2 patients. Botulinum toxin A injection into the orbicularis oculi area also may help to alter the muscle dynamics and improve symptoms in patients with SLK and dry eyes who have elevated blink rates.
      • Shen JF
      • Kusne Y.
      Botulinum toxin A use in dry eye patients with superior limbic keratoconjunctivitis (SLK).
      Tear film deficiency can lead to increased friction between the tarsal and bulbar conjunctivae, contributing to SLK. Dry eye states including keratoconjunctivitis sicca and Sjögren syndrome have been associated with SLK.
      • Goto E
      • Shimmura S
      • Shimazaki J
      • Tsubota K.
      Treatment of superior limbic keratoconjunctivitis by application of autologous serum.
      Keratoconjunctivitis sicca has been reported in up to one quarter of patients with SLK.
      • Nelson JD.
      Superior limbic keratoconjunctivitis (SLK).
      Patients in our series did not have dry eyes preoperatively, although they may have experienced postoperative tear film disturbance contributing to the development of SLK. Diquafosol sodium is a topical solution licensed in Japan for the treatment of dry eye disease.
      • Matsumoto Y
      • Ohashi Y
      • Watanabe H
      • Tsubota K.
      Efficacy and safety of diquafosol ophthalmic solution in patients with dry eye syndrome: a Japanese phase 2 clinical trial.
      It is a P2Y2 receptor agonist that may help to increase fluid and mucin secretion from conjunctival cells.
      • Matsumoto Y
      • Ohashi Y
      • Watanabe H
      • Tsubota K.
      Efficacy and safety of diquafosol ophthalmic solution in patients with dry eye syndrome: a Japanese phase 2 clinical trial.
      Diquasofol sodium was associated with clinical improvement in 1 patient with postoperative dry eyes in our series.
      The immunologic dysregulation theory is supported by the improvement of SLK following treatment with mast cell modulators such as cromolyn sodium
      • Confino J
      • Brown SI.
      Treatment of superior limbic keratoconjunctivitis with topical cromolyn sodium.
      and rebamipide.
      • Takahashi Y
      • Ichinose A
      • Kakizaki H.
      Topical rebamipide treatment for superior limbic keratoconjunctivitis in patients with thyroid eye disease.
      Rebamipide is a quinolone derivative that has anti-inflammatory effects including suppression of cytokines, and it attenuates tumour necrosis factor α–induced barrier dysfunction in the corneal epithelium.
      • Takahashi Y
      • Ichinose A
      • Kakizaki H.
      Topical rebamipide treatment for superior limbic keratoconjunctivitis in patients with thyroid eye disease.
      Clinical improvement was associated with the use of rebamipide in 2 patients as part of other medical therapies in our series. Topical cyclosporine also can be an effective steroid-sparing agent to help relieve the ocular symptoms of SLK.
      • Sahin A
      • Bozkurt B
      • Irkec M.
      Topical cyclosporine a in the treatment of superior limbic keratoconjunctivitis: a long-term follow-up.
      Medical and surgical therapies aim to address the proposed mechanisms in SLK. Initial local treatment options consist of avoiding contact lens wear and topical treatments including lubricants, steroids, vitamin A, cromolyn sodium, and rebamipide.
      • Cher I.
      Superior limbic keratoconjunctivitis: multifactorial mechanical pathogenesis.
      ,
      • Confino J
      • Brown SI.
      Treatment of superior limbic keratoconjunctivitis with topical cromolyn sodium.
      ,
      • Takahashi Y
      • Ichinose A
      • Kakizaki H.
      Topical rebamipide treatment for superior limbic keratoconjunctivitis in patients with thyroid eye disease.
      Lacrimal punctal occlusion and autologous serum drops can be considered in patients with tear film deficiencies.
      • Goto E
      • Shimmura S
      • Shimazaki J
      • Tsubota K.
      Treatment of superior limbic keratoconjunctivitis by application of autologous serum.
      Surgically, lax bulbar conjunctiva can be treated to promote adhesion of the conjunctiva to the sclera (amniotic membrane transplant, silver nitrate/thermocautery).
      • Yamada M
      • Hatou S
      • Mochizuki H.
      Conjunctival fixation sutures for refractory superior limbic keratoconjunctivitis.
      Patient 5 underwent a conjunctival excision with amniotic membrane transplant. Conjunctivoplasty involving resection of the redundant conjunctiva can be effective when other treatment options have failed and was performed in 1 patient in our series.
      • Yokoi N
      • Komuro A
      • Maruyama K
      • Tsuzuki M
      • Miyajima S
      • Kinoshita S.
      New surgical treatment for superior limbic keratoconjunctivitis and its association with conjunctivochalasis.
      In conclusion, clinicians should be aware of the possible association between ptosis surgery and SLK. SLK is an uncommon condition that may be missed because the symptoms are nonspecific, and the characteristic ocular lesions may be hidden under the upper eyelid. Early diagnosis and treatment have the potential to alleviate symptoms that otherwise may be incapacitating for patients.

      Footnotes and Disclosure

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

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