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Increased interdigitation zone visibility on optical coherence tomography following systemic fibroblast growth factor
Jason Charng1, Mary S Attia1, Sukanya Arunachalam1
1Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Nedlands, Western Australia, Australia.
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.
Insights
Fibroblast growth factor receptor (FGFR) inhibitor AZD4547 can cause ocular side effects, including outer retinal changes like subretinal fluid. These changes often resolve without intervention and did not lead to treatment discontinuation.
Area of Science:
- Ophthalmology
- Oncology
- Pharmacology
Background:
- Investigating ocular adverse events and retinal alterations during fibroblast growth factor receptor (FGFR) inhibitor (AZD4547) anticancer therapy.
- Evaluating the safety and impact of FGFR inhibitors on ocular structures.
Purpose of the Study:
- To characterize the spectrum of ocular adverse events associated with AZD4547 treatment.
- To analyze specific retinal changes, including outer and inner retinal layers, using optical coherence tomography (OCT).
Main Methods:
- A sub-study of a phase II clinical trial involving 24 patients receiving AZD4547.
- Regular comprehensive ocular examinations and macular OCT scans were performed.
- OCT parameters, including central retinal thickness (CRT) and macular volume, were extracted and analyzed, with OCT scans segmented into outer and inner retinal layers.
Main Results:
- Ocular adverse events included eyelash elongation (21%) and punctate corneal erosion (8%). One patient developed posterior capsular opacification.
- Retinal changes observed via OCT ranged from increased interdigitation zone (IDZ) visibility (43%) to subretinal fluid pockets (22%), associated with mild visual acuity loss.
- Central retinal thickness increased, particularly in patients with significant retinal changes. Changes were generally bilateral, self-limiting, and improved spontaneously.
Conclusions:
- Ocular side effects did not necessitate AZD4547 dose cessation.
- FGFR inhibition can induce outer retinal changes, manifesting as altered IDZ visibility or subretinal fluid accumulation.
- The findings highlight the importance of monitoring ocular health during FGFR inhibitor therapy.
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