Electrodiagnostic Biomarkers in Paraneoplastic Retinopathy

 

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Abstract

Objective Paraneoplastic retinopathy (PNR) is a rapid-onset photoreceptor and post-photoreceptor dysfunction triggered by a cross-reaction between antigens expressed by the underlying tumour and retinal proteins. The present study aims to determine the electrodiagnostic biomarkers that support the diagnosis of PNR and evaluate the effect of treatment.

Methods A retrospective observational case-controlled study including 25 patients with suspected PNR, of which 11 patients were diagnosed with PNR. The presence of PNR was confirmed based on clinical examination, supported by colour fundus photography, fundus autofluorescence imaging, optical coherence tomography, fluorescein angiography, retinal vessel oximetry, colour test, full-field electroretinogram (ffERG), on-/off ERG, S-cone ERG, and multifocal ERG (mfERG). The relationships between the clinical symptomatology and the effect of therapy were evaluated.

Results All PNR patients (Nr: 11) presented with subjective symptoms of newly reported central vision or visual field deterioration. Posterior segment findings showed a severe patchy-like retinal atrophy, attenuation of the retinal vessels, and a waxy optic disc. Optical coherence tomography revealed a discontinued ISe line, and multiple hyperreflective foci. Retinal vessel oxygen saturation was increased. Multifocal ERG revealed reduced central and paracentral responses and ffERG severely attenuated scotopic-, photopic-, on-/off- and S-cone responses. The colour vision test revealed a tritan-tetartan-weakness. Two of the PNR patients underwent rituximab therapy with no further progression and even recovery of electrodiagnostic responses.

In 1 nPNR (non-paraneoplastic retinopathy) patient (total Nr: 14) pseudoxanthoma elasticum-related retinopathy was the reason for impaired vision. In 3 of 13 patients with bronchopulmonary cancer a MEK- and FGFR-inhibitor- drug toxicity was the reason for the visual deterioration.

Conclusion Careful investigation for signs of central and/or peripheral visual field deterioration must be performed in the presence of history of a co-existing malignancy. The possibility of PNR should be taken into account. The electrodiagnostic biomarkers, suggested in this study, may help to promptly recognise PNR and also to evaluate the effect of implemented therapy.

Zusammenfassung

Ziel Bei der paraneoplastischen Retinopathie (PNR) handelt es sich um eine schnell voranschreitende Photorezeptorendysfunktion, die durch eine Kreuzreaktion zwischen retinalen Proteinen und Antigenen, exprimiert durch eine zugrunde liegende Karzinose, hervorgerufen wird. Im Rahmen dieser Studie sollen die elektrodiagnostischen Biomarker erhoben werden, welche die Diagnose einer PNR unterstützen können und zum Monitoring des therapeutischen Effektes herangezogen werden können.

Methode Es handelt sich um eine retrospektive, fallgesteuerte Studie mit 25 Patienten, bei denen der Verdacht auf eine PNR gestellt wurde. In 11 dieser Patienten wurde eine PNR diagnostiziert. Die Diagnose der PNR wurde anhand der klinischen Untersuchung unter diagnostischer Zuhilfenahme von Fundusfarbfotografie, Fundusautofluoreszenz, Kohärenztomografie der Makula, Fluoreszenzangiografie, Oxymetrie der retinalen Gefäße, Farbtests, Ganzfeld-Elektroretinogramm (ERG), On-/Off-ERG, S-Zapfen-ERG und multifokalem ERG gestellt.

Ergebnisse Alle PNR-Patienten (Nr. 11) beklagten neu aufgetretene zentrale Sehminderungen bzw. Gesichtsfeldausfälle. In der multimodalen, retinalen Bildgebung präsentierten sich fleckige retinale Atrophien, verdünnte retinale Gefäße und blässliche Papillen. Kohärenztomografisch ließen sich Diskontinuitäten im Bereich der ellipsoiden Zone, sowie mehrere hyperreflektive Foci ausmachen. Die Oxymetrie zeigte eine erhöhte Sauerstoffsättigung der retinalen Gefäße. Im multifokalen ERG präsentierten sich verminderte zentrale und parazentrale Antworten, während das Ganzfeld-ERG stark abgeschwächte skotopische, photopische On-/Off- und S-Zapfen-Antworten zeigte. Der Farbsehtest wies eine Schwäche entlang der Tritan- und Tetartan-Achse nach. Zwei der PNR-Patienten wurden mit Rituximab behandelt, worauf sich bei einem eine vollständige Erholung aller Befunde zeigte, während sich beim anderen zwar keine Verbesserung einstellte, aber auch keine Verschlechterung der klinischen und elektrodiagnostischen Befunde dokumentiert werden konnte. In einem der Patienten mit nicht paranoplastischer Retinopathie (nPNR; total Nr. 14) war ein Pseudoxanthoma elasticum ursächlich für die zentrale Sehminderung. In 3 von 13 Patienten, die aufgrund eines Bronchialkarzinoms mit MEK- und FGFR-Inhibitoren therapiert wurden, waren medikamentös-toxische Veränderungen der Grund für die Beschwerden.

Schlussfolgerung Bei Vorhandensein einer zentralen Sehminderung bzw. zentralen und/oder peripheren Gesichtsfelddefekten sollte, insbesondere bei vorbekannten Karzinosen, eine PNR erwogen werden. Die elektrodiagnostischen Befunde, welche in dieser Studie erhoben werden, sollen helfen eine schnelle Diagnose zu stellen und den therapeutischen Effekt zu kontrollieren.

Publication History

Received: 04 October 2023

Accepted: 05 December 2023

Article published online:
23 April 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

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