Trichiasis and dry eye syndrome in two patients on novel fibroblast growth factor receptor inhibitor therapies

Vinson, Kyle B.; Gillette, Wesley M.; Baston, Catherine F.; Leahey, Alan B.

doi:10.1016/j.ajoc.2020.100818

Cited by 7 publications

(5 citation statements)

References 7 publications

(12 reference statements)

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“…AZD4547, a selective inhibitor of FGF receptors (FGFR) 1, 2 and 3, has been proposed as a second‐line anticancer therapy and has undergone human testing 26‐28 . Ocular adverse events from AZD4547 therapy include dry eyes, 26,29,30 central serous retinopathy (CSR) 29 and retinal pigmented epithelium detachment (PED) 28 . The retinal findings following AZD4547 administration were also reported in the only two FGF receptor inhibitors approved by the Food and Drug Administration; erdafitinib 16 and pemigatinib 31 .…”

Section: Introductionmentioning

confidence: 99%

Increased interdigitation zone visibility on optical coherence tomography following systemic fibroblast growth factor receptor 1‐3 tyrosine kinase inhibitor anticancer therapy

Charng

Attia

Arunachalam

et al. 2021

Clinical Exper Ophthalmology

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Background To describe ocular adverse events and retinal changes during fibroblast growth factor receptor (FGFR) inhibitor (AZD4547) anticancer therapy. Methods This is a sub‐study examining ocular adverse effects from AZD4547 therapy (single‐centre, open‐label, single arm phase II clinical trial). Comprehensive ocular examinations were performed 3 weekly in 24 patients. Macular optical coherence tomography (OCT) scan (300 × 250) was obtained at each visit and OCT parameters [central 1 mm retinal thickness (CRT) and total macular volume in central 6 mm] extracted. OCT scans were subdivided into outer (ELM to RPE) and inner (ELM to ILM) layers to compare outer and inner retinal changes. Results In 24 patients, AZD4547 was associated with eyelash elongation (n = 5, 21%) and punctate corneal erosion (n = 2, 8%). One patient developed clinically significant posterior capsular opacification during the study. OCT data were available in 23 patients, retinal changes ranged from an asymptomatic increased visibility of the interdigitation zone (IDZ) (n = 10, 43%) to multilobular subretinal fluid pockets (n = 5, 22%), which was associated with mild visual acuity loss. In a subset of patients (n = 9) with pre‐AZD4547 dosing OCT baseline, CRT increased by mean (SD) of 9 (4) μm in those with IDZ change only compared with 64 (38) μm in those with other retinal changes. Retinal changes tended to be bilateral, self‐limiting and improved over time without medical intervention. Conclusions The ocular signs and symptoms did not result in dose cessation. Posteriorly, FGFR inhibition leads to outer retinal changes ranging from increased visibility of IDZ to distinct, multiple fluid pockets.

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Section: Introductionmentioning

confidence: 99%

Increased interdigitation zone visibility on optical coherence tomography following systemic fibroblast growth factor receptor 1‐3 tyrosine kinase inhibitor anticancer therapy

Charng

Attia

Arunachalam

et al. 2021

Clinical Exper Ophthalmology

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“…The symptoms and signs improved with topical artificial tears, cyclosporine, and repeated mechanical lash epilation. [ 32 ] In earlier phase I/II studies of both AZD4547 and INCB054828, dry skin and mucous membranes (dry mouth at 33.3%,[ 33 ] dry eye at 20%[ 33 ] in AZD4547 trial; dry eyes at 20.3% of all patients treated with pemigatinib) were reported as one of the more common side effects. [ 33 , 34 ] In pemigatinib, the incidence of dry eye correlated with a greater dose of the medication.…”

Section: Resultsmentioning

confidence: 99%

A review on drug-induced dry eye disease

Kam

Zazzo²,

Gregorio³

et al. 2023

Indian Journal of Ophthalmology

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Dry eye disease encompasses a broad range of etiologies and disease subtypes which have similar clinical manifestations. Medications can cause dry eye disease or symptoms of dryness as a side effect by either interfering with the lacrimal gland or meibomian gland function, or both, and by other mechanisms that affect the ocular surface homeostasis. This is important to know and recognize as eliminating the offending medication can reverse the symptoms and, in many cases, prevent further deterioration of the ocular surface inflammation. This review focuses on drugs like systemic isotretinoin and taxanes, which cause meibomian gland dysfunction; immune checkpoint inhibitors that cause lacrimal gland dysfunction; gliptins and topical antiglaucoma medications that cause cicatrizing conjunctivitis; and epidermal growth factor receptor inhibitors, fibroblast growth factor receptor inhibitors, and belantamab mafodotin, which cause mucosal epitheliopathy. Many of these medications, particularly the newer anticancer agents, have only recently been introduced for clinical use, and knowledge and awareness of their ocular side effects are still evolving. This review aims to update ophthalmologists on the drug-induced causes of dry eye disease or symptoms of dryness, which is avoidable by discontinuation of the incriminating agent or can be mitigated by reducing the dose or frequency of usage.

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“…11 Previous reports of the ocular AE of the FGFR inhibitors mainly focused on the cornea and retina, but the change of MG was not mentioned. [2][3][4] When initiating the therapy, oncologists are actually playing an essential role in educating patients about the potential of AEs. Without the oncologist's referral, the ophthalmologists may have no access to these patients before the ophthalmologists start the treatment.…”

Section: Discussionmentioning

confidence: 99%

“…1 Anticancer drugs targeting fibroblast growth factor (FGF) receptors (FGFRs) were reported to have a high incidence of dry eye, but the mechanism stays unclear. [2][3][4] We hypothesize that anticancer drugs targeting FGFRs could cause meibomian gland (MG) dysfunction (MGD). MGD is the leading cause of dry eye, but its pathogenesis is unclear.…”

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confidence: 99%

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Eyes on the Lid: The Impact of Fibroblast Growth Factor Receptor Targeting Drug on Human Meibomian Gland

Chen,

Liu,

Zheng

et al. 2023

Eye &Amp; Contact Lens: Science &Amp; Clinical Practice

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Objective: To determine whether fibroblast growth factor receptor (FGFR)-targeting drug could impact human meibomian gland. Methods: We followed up with three patients who were using pemigatinib for 4 to 10 weeks. The patients were evaluated for their ocular surface disease index, best-corrected visual acuity, Schirmer test, cornea staining, meibum expressibility score, tear meniscus height, noninvasive tear film breakup time, and meibomian gland area. The distribution of the FGFR family, FGF7, and FGF10 were evaluated by immunofluorescence staining and Western blot in fresh tarsal tissues from deidentified patients who underwent lid plastic surgeries. Results: All patients developed apparent meibomian gland atrophy, shortening and narrowing of ducts, and significantly increased meibum expressibility and decreased noninvasive tear film breakup time within 5 to 8 weeks. Laboratory evaluations confirmed that human meibomian gland expresses abundant fibroblast growth factor receptors. Conclusions: These findings indicate that meibomian gland is a target tissue of FGFR inhibitors, and patients who use these drugs may develop meibomian gland dysfunction.

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Trichiasis and dry eye syndrome in two patients on novel fibroblast growth factor receptor inhibitor therapies

Cited by 7 publications

References 7 publications

Increased interdigitation zone visibility on optical coherence tomography following systemic fibroblast growth factor receptor 1‐3 tyrosine kinase inhibitor anticancer therapy

Increased interdigitation zone visibility on optical coherence tomography following systemic fibroblast growth factor receptor 1‐3 tyrosine kinase inhibitor anticancer therapy

A review on drug-induced dry eye disease

Eyes on the Lid: The Impact of Fibroblast Growth Factor Receptor Targeting Drug on Human Meibomian Gland

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