Gene therapy has emerged as a research topic of choice in recent years. The eye in particular is one of few organs of the body for which gene therapy has received Food and Drug Administration approval, and it remains a field of great interest for gene therapy development. However, its associated immune and inflammatory reactions may render the treatment ineffective or harmful, which are of particular concern for the eyes due to their susceptibility to inflammation. The severity of immune and inflammatory reactions depends on the choice of vector and its route of administration. Furthermore, most preclinical and clinical studies have shown that the dose of vectors is correlated with the degree of humoral response and ocular inflammation. The route of administration directly impacts the degree of immune and inflammatory reaction. Subretinal delivery produces a weaker humoral response than the intravitreal route. However, some studies have demonstrated that the subretinal delivery induces a stronger inflammatory reaction. On the other hand, several instances of vision loss due to severe late onset intraocular inflammation were reported in a clinical trial involving intravitreal delivery of viral vectors. When compared with the intravitreal route, suprachoroidal gene delivery has been shown to produce weaker humoral response. However, unlike the subretinal space, the suprachoroidal space is not known to have immune privilege status. Inflammatory reactions following ocular gene therapy are typically mild and most clinical and preclinical studies have shown that they can be controlled with topical, local or systemic steroids. However, severe inflammatory responses may occur and require aggressive management to avoid permanent vision loss. Further investigations are required to elucidate and expand our knowledge of inflammatory reactions, and their optimal management, following ocular gene therapy.
Purpose To describe structural changes in corneal epithelium using anterior segment optical coherence tomography (AS-OCT) in two relapsed and refractory multiple myeloma (RRMM) patients with bilateral belantamab-associated superficial keratopathy (BASK). Observations: case 1 A 56-year-old male who was diagnosed with RRMM and initiated on belantamab mafodotin, presented on day 42 (three weeks after the second infusion) with decreased pinhole visual acuity from 20/20 and 20/25 to 20/70 and 20/50 in the right eye and left eye, respectively. Slit-lamp examination revealed moderate superficial keratopathy with microcystic-like epithelial changes (MECs) in the paracentral cornea in both eyes. AS-OCT demonstrated increased bilateral heterogeneous signal intensity and hyperreflective lesions as well as increased thickness in the paracentral corneal epithelium with uninvolved central cornea. Given bilateral MECs, the third infusion was withheld, and then given on day 62 after five weeks of drug-free interval. Although MECs had improved on day 82, pinhole visual acuity remained at 20/50 and 20/40 in the right eye and the left eye. AS-OCT showed that hyperreflective lesions mostly resolved and corneal epithelial thickness returned to baseline, despite a slightly increased persisting heterogeneous signal intensity in the peripheral corneal epithelium in both eyes. Case 2 A 77-year-old male with RRMM was started on belantamab mafodotin infusions. His pinhole visual acuity decreased from 20/40 and 20/30 at baseline to 20/60 and 20/40 on day 41 (three weeks after the second infusion) in the right eye and left eye, respectively. Slit-lamp examination showed diffuse, moderate MECs in both eyes, which was more severe in the peripheral cornea. AS-OCT demonstrated increased bilateral heterogeneous signal intensity and hyperreflective lesions in the corneal epithelium, which are more severe in the right eye along with increased corneal epithelial thickness. Therefore, belantamab mafodotin was withheld. Conclusions and Impotance AS-OCT objectively demonstrated structural changes such as signal intensity and thickness alterations with hyperreflective lesions in the corneal epithelium related to BASK. AS-OCT might be useful for clinicians to monitor ocular surface adverse events in RRMM patients receiving belantamab mafodotin and to adjust therapeutic plans for the patients.
Purpose Diopsys ® NOVA fixed-luminance flicker full-field electroretinogram (ffERG) device is a potential adjunct to conventional flicker ffERG testing for assessing cone cell function. Magnitude of measured electrical response is known to vary with pupil size in conventional ffERG testing. The index study characterizes the relationship between magnitude of measured electrical activity and pupil size, both pupil diameter and pupil area, for this device. Methods Seventeen patients (34 eyes) with no known ocular diseases were enrolled in the study. Electrophysiologic function of cone cells was evaluated using fixed-luminance flicker ffERG before and after dilation. Linear regression models, with inter-eye correlations controlled as fixed-effects, were used to characterize the effect of pupil dilation on the magnitude of the measured responses. Results Mean age of study patients was 33.5 (standard deviation 7.4 years), and 35.3% of the subjects were female. Mean value of electrical response magnitude was 10.07±2.79µV before dilation and 15.30±4.08µV after dilation. The correlations of ERG magnitude with pupil diameter and with pupil area were not significant for either dilated or undilated eyes considered separately but were highly significant (p<0.001) for dilated and undilated eyes considered in aggregate. ERG magnitude tended to increase by 1.08 µV for every 1 mm increase in pupillary diameter. Conclusion An increase in pupil size, both pupil diameter and pupil area, is significantly associated with an increase in flicker ffERG magnitude recorded by the Diopsys device, suggesting that pupil size should be measured and considered when making clinical judgments based on the flicker ffERGs recorded by the device, and that pupil size-specific reference ranges could improve the clinical utility of the device.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.