Topical Losartan for Treating Corneal Fibrosis (Haze): First Clinical Experience

Pereira-Souza, Amanda Luiza; Ambrósio, Renato; Bandeira, Francisco; Salomão, Marcella Q.; Lima, A. S.; Wilson, Steven E.

doi:10.3928/1081597x-20221018-02

Cited by 27 publications

(17 citation statements)

References 16 publications

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“…Even when this treatment is effective in closing a PED, however, the affected cornea frequently has moderate to severe scarring stromal fibrosis that limits the vision in the eye. Several recent rabbit studies, 38 – 40 as well as a clinical report in humans, 41 , 42 have demonstrated the efficacy of topical losartan in decreasing stromal myofibroblasts and fibrosis after a variety of corneal injuries. It may be that combined topical Oxervate and topical losartan could provide the best treatment for neurotropic corneas with a PED and stromal scarring fibrosis.…”

Section: Discussionmentioning

confidence: 98%

Cell Biology of Spontaneous Persistent Epithelial Defects After Photorefractive Keratectomy in Rabbits

Sampaio

Martínez

Shiju

et al. 2023

Trans. Vis. Sci. Tech.

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Purpose To evaluate wound healing in rabbit corneas that developed a spontaneous persistent epithelial defect (PED) after photorefractive keratectomy (PRK). Methods Forty-eight 10- to 15-week-old female New Zealand White rabbits weighing 2.5 to 3.0 kg underwent either –3 diopter (D) or –9 D PRK to generate a series of corneas to study wound healing after injury. During that series, seven corneas developed a PED detected with 1% fluorescein staining at a slit lamp that either did not have epithelial closure by 1 week after surgery or subsequently had the closed epithelium break down to form a PED 2 to 3 weeks after surgery. The corneas had slit-lamp photography, with and without 1% fluorescein, and were removed from the normal PRK series. Each PED cornea was evaluated using immunohistochemistry for the myofibroblast marker α–smooth muscle actin (α-SMA), keratocyte marker keratocan, and mesenchymal cell marker vimentin, as well as basement membrane components perlecan and collagen type IV. Results All seven corneas that had PRK with a PED, even the two evaluated at only 1 week after PRK, had α-SMA–positive myofibroblasts populating the anterior stroma within the PED, along with comingled α-SMA–negative cells that were likely corneal fibroblasts and possibly bone marrow–derived fibrocytes. Both perlecan and collagen type IV accumulated in the anterior stroma of the epithelial defects without an epithelial basement membrane, likely produced by corneal fibroblasts to modulate transforming growth factor–β entering the stroma from the tears and peripheral epithelium. Conclusions Corneas with a PED that occurred following PRK (a procedure that produces a transient neurotropic state in the cornea) had myofibroblasts populating the superficial stroma within the epithelial defect as early as 1 week after the surgery. Translational Relevance Pharmacologic treatments that trigger myofibroblast apoptosis, including topical losartan, could facilitate decreased scarring fibrosis in corneas with a PED.

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Section: Discussionmentioning

confidence: 98%

Cell Biology of Spontaneous Persistent Epithelial Defects After Photorefractive Keratectomy in Rabbits

Sampaio

Martínez

Shiju

et al. 2023

Trans. Vis. Sci. Tech.

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“…I would recommend initiating treatment with 0.8 mg/mL losartan drops 6 times a day in the eye with the herpes zoster scar. 1–3 I would continue that treatment for at least 6 months, along with oral valacyclovir to prevent recurrence of the infection because antiherpetics have been shown to be effective in both herpes zoster and herpes simplex keratitis reactivation. Importantly, several case reports in humans not yet published have responded to topical losartan even years after the original injury.…”

Section: Steven E Wilson MDmentioning

confidence: 99%

“…Although in our environment we do not currently have this therapeutic option and, therefore, we do not yet have experience with it, there are already described in the literature cases of haze improved or resolved with the application of topical losartan 4 to 6 times a day, for at least 6 months, without appearing to pose any additional risk to the patient. 4 Based on this, this topical pharmacological treatment could be considered before deciding on a surgical option, although it is true that in this very young patient, with the other eye with hardly any visual acuity, we could enter into the moral conflict of what is more beneficial for the patient, whether to delay a possible recovery of visual acuity by trying a more conservative and time-consuming pharmacological treatment or directly opting for surgery, with the most appropriate technique based on the characteristics that we have previously described. In our opinion, it is important to weigh the physical and psychological risks/benefits of this patient and his family and involve them in the decision.…”

Section: Fernando Llovet MD Phdmentioning

confidence: 99%

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Addressing corneal opacity after herpes zoster infection

Santhiago,

Sampaio,

Arroyo

et al. 2024

J Cataract Refract Surg

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A 15-year-old boy was referred for corneal opacity evaluation. The patient had a previous herpes zoster virus (HZV) infection—varicella-zoster virus (VZV)—with ocular manifestation 1 year ago. After the infection, he developed a central corneal scar and decreased corrected distance visual acuity (CDVA) in the right eye. The slitlamp examination showed the right eye with central corneal opacity (involving anterior stroma), lacuna area between the haze, fluorescein negative, and no vascularization near the scar (Figure 1 JOURNAL/jcrs/04.03/02158034-202406000-00019/figure1/v/2024-05-21T162725Z/r/image-tiff ). The patient had been treated with oral valacyclovir and topical corticosteroids without any improvement of visual acuity or changes in opacity within the 1-year follow-up. His CDVA was 20/200 (−4.50 −0.75 × 25) in the right eye and counting fingers (−4.00) in the left eye. Intraocular pressure was 12 mm Hg in both eyes. Fundoscopy was normal in the right eye, but he had a macular scar in the left eye (diagnosed when he was 7 years). The left eye had no cornea signs. The patient has no comorbidity or previous surgeries. Considering this case, a corneal central scar in a 15-year-old boy, legally single eye only, and assuming it is an opacity in the anterior stroma, would you consider surgery for this patient? If so, which would you choose: Would you consider an excimer laser treatment of his ametropia while partially removing his opacity, a phototherapeutic keratectomy (PTK), or a PTK followed by a topography-guided treatment, femtosecond laser-assisted anterior lamellar keratoplasty (FALK), or deep anterior lamellar keratoplasty (DALK) or penetrating keratoplasty (depending on the scar depth)? Would you consider prophylactic acyclovir during and after surgery? Would you consider any other surgical step to prevent delayed corneal healing-persistent epithelial defect? Before the surgical approach, would you consider treating this patient with topical losartan (a transforming growth factor [TGF]-β signaling inhibitor)? Would you first perform the surgery (which one) and then start the medication? Furthermore, if so, how long would you treat this patient? Would you consider treatment with another medication?

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“…Studies in rabbits supported the efficacy of topical losartan in decreasing scarring fibrosis after Descemetorhexis, alkali burn, and photorefractive keratectomy injuries, and in case reports of humans with scarring fibrosis after surgical complications. Clinical studies are needed to explore the efficacy and safety of topical losartan in the prevention and treatment of corneal scarring fibrosis, and other eye disorders where TGF beta has a role in pathophysiology [39–42,43 ▪▪ ].…”

Section: Managementmentioning

confidence: 99%

Cataract surgery in setting of ocular surface disease

Sarnicola,

De Bernardo

et al. 2023

Current Opinion in Ophthalmology

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Purpose of review The purpose of this article is to review the available strategies to successfully identify and manage ocular surface disease (OSD) pre, intra and post-cataract surgery. Recent findings Cataract surgery and OSD have an intricate relationship: the surgical procedure can induce or exaggerate OSD symptoms, while OSD can negatively impact surgical refractive outcomes and increase the rate of postoperative complications. Summary Improving the health and stability ocular surface is the key to enhance post cataract surgery refractive outcomes and avoid complications. This is pivotal for patients affected by severe OSD, but is also important for patients with minimal signs or symptoms. A correct diagnosis and a stepwise approach are the keys to improve the quality of life of such patients.

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Topical Losartan for Treating Corneal Fibrosis (Haze): First Clinical Experience

Cited by 27 publications

References 16 publications

Cell Biology of Spontaneous Persistent Epithelial Defects After Photorefractive Keratectomy in Rabbits

Cell Biology of Spontaneous Persistent Epithelial Defects After Photorefractive Keratectomy in Rabbits

Addressing corneal opacity after herpes zoster infection

Cataract surgery in setting of ocular surface disease

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