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Use of ripasudil for rapid resolution of acute hydrops in keratoconus

Published:December 21, 2021DOI:https://doi.org/10.1016/j.jcjo.2021.11.009
      Acute corneal hydrops (CH) is characterized by marked stromal edema from the influx of aqueous humour through a tear in Descemet membrane.
      • Sharma N
      • Maharana PK
      • Jhanji V
      • Vajpayee RB.
      Management of acute corneal hydrops in ectatic corneal disorders.
      It is predominantly seen in patients with corneal ectasia and reported in up to 3% of patients with keratoconus.
      • Sharma N
      • Maharana PK
      • Jhanji V
      • Vajpayee RB.
      Management of acute corneal hydrops in ectatic corneal disorders.
      ,
      • Miyata K
      • Tsuji H
      • Tanabe T
      • Mimura Y
      • Amano S
      • Oshika T.
      Intracameral air injection for acute hydrops in keratoconus.
      CH presents with an acute decrease in visual acuity, photophobia, and pain.
      • Sharma N
      • Maharana PK
      • Jhanji V
      • Vajpayee RB.
      Management of acute corneal hydrops in ectatic corneal disorders.
      Conservative management of CH includes topical hypertonic saline solution, cycloplegics, topical corticosteroids, topical antibiotics, and a bandage soft contact lens if needed for comfort.
      • Sharma N
      • Maharana PK
      • Jhanji V
      • Vajpayee RB.
      Management of acute corneal hydrops in ectatic corneal disorders.
      ,
      • Miyata K
      • Tsuji H
      • Tanabe T
      • Mimura Y
      • Amano S
      • Oshika T.
      Intracameral air injection for acute hydrops in keratoconus.
      With these conservative measures, CH often resolves in 2–4 months.
      • Miyata K
      • Tsuji H
      • Tanabe T
      • Mimura Y
      • Amano S
      • Oshika T.
      Intracameral air injection for acute hydrops in keratoconus.
      This long duration of corneal edema not only prolongs the patient's discomfort but also can have lasting sequelae such as infectious keratitis, corneal neovascularization, stromal scarring, corneal perforation, and the need for corneal transplantation.
      • Sharma N
      • Maharana PK
      • Jhanji V
      • Vajpayee RB.
      Management of acute corneal hydrops in ectatic corneal disorders.
      ,
      • Miyata K
      • Tsuji H
      • Tanabe T
      • Mimura Y
      • Amano S
      • Oshika T.
      Intracameral air injection for acute hydrops in keratoconus.
      In this article, we describe the successful use of the topical Rho kinase inhibitor ripasudil hydrochloride hydrate (Glanatec Ophthalmic Solution 0.4%, Kowa Co Ltd, Nagoya, Japan) for noninvasive treatment of CH with rapid resolution of corneal edema in 21 days.
      A 32-year-old male presented with a 2-week history of decreased vision in the central and inferior visual field of the left eye with irritation and foreign-body sensation. He had already been prescribed topical fluorometholone, sodium chloride 5% hypertonic ophthalmic ointment, and topical chloramphenicol by another provider, with no improvement. His distance corrected visual acuity with glasses was 6/6 OD and 6/60 OS. Anterior segment examination demonstrated a large central corneal edema of the left eye with central pachymetry above 2000 µm. He was diagnosed with CH and started on topical ripasudil 0.4% twice a day in the left eye in addition to topical chloramphenicol.
      At the 3-week follow-up, his symptoms had improved significantly, but his distance corrected visual acuity of the left eye remained poor at 3/60. His corneal edema had resolved completely at this point but was replaced by visually significant stromal scarring. His corneal tomography and anterior segment optical coherence tomography images at presentation and 3-week follow-up are shown in Figure 1.
      Fig 1
      Fig. 1(A) Corneal tomography of the left eye depicting axial curvature, corneal thickness, and front and back elevation before and 3 weeks after ripasudil treatment. (B) Anterior segment optical coherence tomography of the left eye before and 3 weeks after ripasudil treatment.
      Because of the poor visual acuity, a manual predescemetic deep anterior lamellar keratoplasty was offered at an early stage, 3 weeks after resolution of his CH. At 14 months after his transplant, his graft was clear (Fig. 2), and his visual acuity with glasses was 6/9 in the affected eye.
      Fig 2
      Fig. 2Anterior segment photograph of the left eye following manual predescemetic deep anterior lamellar keratoplasty.
      In this article, we report the successful use of ripasudil in rapid resolution of CH in keratoconus. To accelerate the resolution of CH, various surgical interventions have been used. Intracameral injection of air or gas (sulfur hexafluoride [SF6] or perflouropropane [C3F8]) has been used to tamponade the tear and prevent further leakage of fluid into the stroma.
      • Miyata K
      • Tsuji H
      • Tanabe T
      • Mimura Y
      • Amano S
      • Oshika T.
      Intracameral air injection for acute hydrops in keratoconus.
      • Panda A
      • Aggarwal A
      • Madhavi P
      • et al.
      Management of acute corneal hydrops secondary to keratoconus with intracameral injection of sulfur hexafluoride (SF6).
      • Basu S
      • Vaddavalli PK
      • Ramappa M
      • Shah S
      • Murthy SI
      • Sangwan VS.
      Intracameral perfluoropropane gas in the treatment of acute corneal hydrops.
      • Shah SG
      • Sridhar MS
      • Sangwan VS.
      Acute corneal hydrops treated by intracameral injection of perfluoropropane (C3F8) gas.
      • Mohebbi M
      • Pilafkan H
      • Nabavi A
      • Mirghorbani M
      • Naderan M.
      Treatment of acute corneal hydrops with combined intracameral gas and approximation sutures in patients with corneal ectasia.
      • Siebelmann S
      • Händel A
      • Matthaei M
      • Bachmann B
      • Cursiefen C.
      Microscope-integrated optical coherence tomography-guided drainage of acute corneal hydrops in keratoconus combined with suturing and gas-aided reattachment of Descemet membrane.
      • Zhao Z
      • Wu S
      • Ren W
      • et al.
      Compression sutures combined with intracameral air injection versus thermokeratoplasty for acute corneal hydrops: a prospective-randomised trial.
      In multiple comparative studies, intracameral gas or air injection appears to result in faster resolution of CH in as early as 3 weeks.
      • Panda A
      • Aggarwal A
      • Madhavi P
      • et al.
      Management of acute corneal hydrops secondary to keratoconus with intracameral injection of sulfur hexafluoride (SF6).
      ,
      • Basu S
      • Vaddavalli PK
      • Ramappa M
      • Shah S
      • Murthy SI
      • Sangwan VS.
      Intracameral perfluoropropane gas in the treatment of acute corneal hydrops.
      However, multiple injections often were needed, and potential complications of intraocular pressure spikes, cataract formation, pupillary block, and intrastromal gas migration have been reported.
      • Panda A
      • Aggarwal A
      • Madhavi P
      • et al.
      Management of acute corneal hydrops secondary to keratoconus with intracameral injection of sulfur hexafluoride (SF6).
      ,
      • Basu S
      • Vaddavalli PK
      • Ramappa M
      • Shah S
      • Murthy SI
      • Sangwan VS.
      Intracameral perfluoropropane gas in the treatment of acute corneal hydrops.
      The patient is also required to keep a supine position for optimal gas placement in the anterior chamber.
      • Miyata K
      • Tsuji H
      • Tanabe T
      • Mimura Y
      • Amano S
      • Oshika T.
      Intracameral air injection for acute hydrops in keratoconus.
      Additionally, corneal compression sutures have been employed to approximate the edges of Descemet membrane, especially for large defects with cleft formation.
      • Mohebbi M
      • Pilafkan H
      • Nabavi A
      • Mirghorbani M
      • Naderan M.
      Treatment of acute corneal hydrops with combined intracameral gas and approximation sutures in patients with corneal ectasia.
      • Siebelmann S
      • Händel A
      • Matthaei M
      • Bachmann B
      • Cursiefen C.
      Microscope-integrated optical coherence tomography-guided drainage of acute corneal hydrops in keratoconus combined with suturing and gas-aided reattachment of Descemet membrane.
      • Zhao Z
      • Wu S
      • Ren W
      • et al.
      Compression sutures combined with intracameral air injection versus thermokeratoplasty for acute corneal hydrops: a prospective-randomised trial.
      • Soleimani M
      • Mirshahi R
      • Tabatabaei SA
      • Momenaei B
      • Salabati M
      • Ghomi MR.
      Using intracameral vital dye as a guide for venting incision in acute corneal hydrops.
      • Subudhi P
      • Khan Z
      • Subudhi BNR
      • Sitaram S.
      To show the efficacy of compressive sutures alone in the management of acute hydrops in a keratoconus patient.
      Other interventions include venting incisions,
      • Siebelmann S
      • Händel A
      • Matthaei M
      • Bachmann B
      • Cursiefen C.
      Microscope-integrated optical coherence tomography-guided drainage of acute corneal hydrops in keratoconus combined with suturing and gas-aided reattachment of Descemet membrane.
      ,
      • Soleimani M
      • Mirshahi R
      • Tabatabaei SA
      • Momenaei B
      • Salabati M
      • Ghomi MR.
      Using intracameral vital dye as a guide for venting incision in acute corneal hydrops.
      multifocal cauterization,
      • Wylegala E
      • Tarnawska D.
      Amniotic membrane transplantation with cauterization for keratoconus complicated by persistent hydrops in mentally retarded patients.
      and the use of platelet-rich plasma intracameral injection.
      • Alio JL
      • Toprak I
      • Rodriguez AE.
      Treatment of severe keratoconus hydrops with intracameral platelet-rich plasma injection.
      None of these procedures has been consistently successful at resolving CH in less than 3 weeks.
      Predescemetic deep anterior lamellar keratoplasty (DALK) has been described as an intervention for acute CH.
      • Jacob S
      • Narasimhan S
      • Agarwal A
      • Sambath J
      • Umamaheshwari G
      • Saijimol AI.
      Primary modified predescemetic deep anterior lamellar keratoplasty in acute corneal hydrops.
      The rapid resolution of edema in this case was unexpected. Although it provided rapidly improved comfort and re-formation of the epithelial barrier, it was not accompanied by improved visual acuity. A scleral lens may have been an option in this case, but a manual predescemetic deep anterior lamellar keratoplasty was chosen as a more definitive method of resolution. The clear view created allowed good visualization of planes and provided confidence that deeper layers were intact during surgery.
      Rho kinase inhibitors have been reported previously to promote endothelial cell delamination and migration, accelerating endothelial wound healing.
      • Syed ZA
      • Rapuano CJ.
      Rho kinase (ROCK) inhibitors in the management of corneal endothelial disease.
      There is growing evidence supporting their utility in multiple corneal pathologies. Our centre has reported positive experience with the use of Rho kinase inhibitors as an adjuvant to Descemet stripping only or descemetorhexis without endothelial keratoplasty.
      • Moloney G
      • Petsoglou C
      • Ball M
      • et al.
      Descemetorhexis without grafting for Fuchs endothelial dystrophy: supplementation with topical ripasudil.
      • Garcerant D
      • Hirnschall N
      • Toalster N
      • Zhu M
      • Wen L
      • Moloney G.
      Descemet's stripping without endothelial keratoplasty.
      • Artieda JA
      • Wells M
      • Devasahayam RN
      • Moloney G.
      5-year outcomes of Descemet stripping only in Fuchs dystrophy.
      • Moloney G
      • Congote D
      • Hirnschall N
      • et al.
      Descemet stripping only supplemented with topical ripasudil for Fuchs endothelial dystrophy: 12-month outcomes of the Sydney Eye Hospital Study.
      • Kassumeh S
      • von Studnitz A
      • Priglinger SG
      • et al.
      Ex vivo excimer laser ablation of cornea guttata and ROCK inhibitor–aided endothelial recolonization of ablated central cornea.
      Similarly, netarsudil has been reported to assist with the treatment of corneal endothelial disease in iridocorneal endothelial syndrome and penetrating keratoplasty graft failure.
      • Davies E.
      Case series: Novel utilization of Rho-kinase inhibitor for the treatment of corneal edema.
      This is the first published report of the use of a Rho kinase inhibitor for the management of CH and offers a well-tolerated, noninvasive alternative to the surgical techniques used. The mechanism of healing is consistent with our understanding of Rho kinase inhibitors as promoters of cell migration across endothelial defects, such as those occurring in CH.
      We acknowledge the lack of a control to confirm this finding as significant. In CH, it may be impossible to design such a study. Nevertheless, we present the fastest published resolution of CH with medical therapy and feel this to be of significance even in isolation.

      Footnotes and Disclosure

      Greg Moloney was a previous consultant of Kowa India Private Limited, manufacturers of Ripasudil; the other authors have no conflicts of interest to disclose. Use of ripasudil for corneal hydrops is an off-label use of the medication.

      References

        • Sharma N
        • Maharana PK
        • Jhanji V
        • Vajpayee RB.
        Management of acute corneal hydrops in ectatic corneal disorders.
        Curr Opin Ophthalmol. 2012; 23: 317-323
        • Miyata K
        • Tsuji H
        • Tanabe T
        • Mimura Y
        • Amano S
        • Oshika T.
        Intracameral air injection for acute hydrops in keratoconus.
        Am J Ophthalmol. 2002; 133: 750-752
        • Panda A
        • Aggarwal A
        • Madhavi P
        • et al.
        Management of acute corneal hydrops secondary to keratoconus with intracameral injection of sulfur hexafluoride (SF6).
        Cornea. 2007; 26: 1067-1069
        • Basu S
        • Vaddavalli PK
        • Ramappa M
        • Shah S
        • Murthy SI
        • Sangwan VS.
        Intracameral perfluoropropane gas in the treatment of acute corneal hydrops.
        Ophthalmology. 2011; 118: 934-939
        • Shah SG
        • Sridhar MS
        • Sangwan VS.
        Acute corneal hydrops treated by intracameral injection of perfluoropropane (C3F8) gas.
        Am J Ophthalmol. 2005; 139: 368-370
        • Mohebbi M
        • Pilafkan H
        • Nabavi A
        • Mirghorbani M
        • Naderan M.
        Treatment of acute corneal hydrops with combined intracameral gas and approximation sutures in patients with corneal ectasia.
        Cornea. 2020; 39: 258-262
        • Siebelmann S
        • Händel A
        • Matthaei M
        • Bachmann B
        • Cursiefen C.
        Microscope-integrated optical coherence tomography-guided drainage of acute corneal hydrops in keratoconus combined with suturing and gas-aided reattachment of Descemet membrane.
        Cornea. 2019; 38: 1058-1061
        • Zhao Z
        • Wu S
        • Ren W
        • et al.
        Compression sutures combined with intracameral air injection versus thermokeratoplasty for acute corneal hydrops: a prospective-randomised trial.
        Br J Ophthalmol. 2021; 105: 1645-1650
        • Soleimani M
        • Mirshahi R
        • Tabatabaei SA
        • Momenaei B
        • Salabati M
        • Ghomi MR.
        Using intracameral vital dye as a guide for venting incision in acute corneal hydrops.
        Eur J Ophthalmol. 2019; 29: 694-697
        • Subudhi P
        • Khan Z
        • Subudhi BNR
        • Sitaram S.
        To show the efficacy of compressive sutures alone in the management of acute hydrops in a keratoconus patient.
        BMJ Case Rep. 2017; 2017bcr2016218843
        • Wylegala E
        • Tarnawska D.
        Amniotic membrane transplantation with cauterization for keratoconus complicated by persistent hydrops in mentally retarded patients.
        Ophthalmology. 2006; 113: 561-564
        • Alio JL
        • Toprak I
        • Rodriguez AE.
        Treatment of severe keratoconus hydrops with intracameral platelet-rich plasma injection.
        Cornea. 2019; 38: 1595-1598
        • Jacob S
        • Narasimhan S
        • Agarwal A
        • Sambath J
        • Umamaheshwari G
        • Saijimol AI.
        Primary modified predescemetic deep anterior lamellar keratoplasty in acute corneal hydrops.
        Cornea. 2018; 37: 1328-1333
        • Syed ZA
        • Rapuano CJ.
        Rho kinase (ROCK) inhibitors in the management of corneal endothelial disease.
        Curr Opin Ophthalmol. 2021; 32: 268-274
        • Moloney G
        • Petsoglou C
        • Ball M
        • et al.
        Descemetorhexis without grafting for Fuchs endothelial dystrophy: supplementation with topical ripasudil.
        Cornea. 2017; 36: 642-648
        • Garcerant D
        • Hirnschall N
        • Toalster N
        • Zhu M
        • Wen L
        • Moloney G.
        Descemet's stripping without endothelial keratoplasty.
        Curr Opin Ophthalmol. 2019; 30: 275-285
        • Artieda JA
        • Wells M
        • Devasahayam RN
        • Moloney G.
        5-year outcomes of Descemet stripping only in Fuchs dystrophy.
        Cornea. 2020; 39: 1048-1051
        • Moloney G
        • Congote D
        • Hirnschall N
        • et al.
        Descemet stripping only supplemented with topical ripasudil for Fuchs endothelial dystrophy: 12-month outcomes of the Sydney Eye Hospital Study.
        Cornea. 2021; 40: 320-326
        • Kassumeh S
        • von Studnitz A
        • Priglinger SG
        • et al.
        Ex vivo excimer laser ablation of cornea guttata and ROCK inhibitor–aided endothelial recolonization of ablated central cornea.
        Acta Ophthalmol. 2020; 98: e773-e780
        • Davies E.
        Case series: Novel utilization of Rho-kinase inhibitor for the treatment of corneal edema.
        Cornea. 2021; 40: 116-120