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Vitreomacular traction (VMT) syndrome has only been surgically treated for a long time. Recently,enzymatic vitreolysis with ocriplasmin has emerged as a possible option to release VMT and, in some cases, close full thickness macular holes (FTMHs). Despite its clinical relevance, gathering information about the ocriplasmin-induced alterations of the Inner Limiting Membrane (ILM) of the retina in a clinical study is a complex task, mainly because of the inter-individual variability among patients. To obtain more insights into the mechanism underlying the drug action, we studied in-vitro the mechanical and morphological changes of the ILM using Atomic Force Microscopy (AFM). To this aim, we measured the ILM average Young’s modulus (YM), hysteresis (H) and adhesion work (A) over time under ocriplasmin treatment. Our data unveil a time-dependent increase in the 34 membrane YM of 19% of its initial value, along with changes in its adhesive and dissipative behavior. Such modifications well correlate with the morphological alterations detected in the AFM imaging mode. Taken all together, the results here presented provide more insights into the mechanism underlying the ocriplasmin action in-vivo, suggesting that it is only able to alter the top-most layer of the vitreal side of the membrane, not compromising the inner ILM structure.

BACKGROUND: To study the photopic negative response of the full-field photopic ERG in Stargardt patients with pathogenic variants in the ABCA4 gene. METHODS: A retrospective analysis of 35 Stargardt patients with ABCA4 gene pathogenic variants, compared to normal age matched controls. Patients were clinically followed at the Ophthalmology Department of Fondazione Policlinico Universitario A. Gemelli/Università Cattolica del Sacro Cuore - Rome, Italy. RESULTS: The photopic negative response of the full-field photopic ERG was compromised in most Stargardt patients. In the presence of a normal B-wave, the amplitude ratio between the photopic negative response and the B-wave displayed a 97% accuracy in detecting diseased eyes (ROC curves). CONCLUSIONS: In Stargardt patients with ABCA4 pathogenic mutations, the photopic negative response of the full-field photopic ERG is a very sensitive disease read-out. Its inclusion in standard ERG analysis would be a no-cost addition of practical consequence in the follow-up of Stargardt disease. The early impairment of the photopic negative response suggests that inner retinal function might be affected in Stargardt disease earlier than previously acknowledged.