Author: Alfonso Senatore (Italy)
Co-authors: Giuseppe Frascogna, Gianluca Monterosso, Antonio Toso
Purpose
The aim of this abstract is to describe the pattern of retinal damage in two patients that showed an adverse dye-related event after macular surgery for pucker. Since the day after an unusual retinal inflammation was noted in both patients and during the follow-ups the absence of recovery with progressive degeneration of stained tissues became evident. Vital dyes are commonly used in chromo-vitrectomy and macular surgery. Their toxicity is clearly reported in pre-clinical, clinical and real-life studies, with the report of a possible compromission of cell viability and their apoptosis. In our cases, in the hypothesis of a combined effect of dye- and light- mediated toxicity a similitude with the most common inherited macular dystrophy was made, the Stargardt’ disease. This retinal dystrophy recognizes the formation of a peculiar lipofuscin, the A2E, in photoreceptors, that are progressively intoxicated by this compound. A biallelic mutation in ABCA4 gene is considered causative for this disease as for other retinal degenerations, that show the sparing of the parapapillary area (in up to 98% of patients) as common marker. In all of them the role of light as mediator of this damage has been hypothesized and partially demonstrated, but still under research.
Setting/Venue
The setting of our findings was the ophthalmology complex operative unit of “spoke” hospital “Alto Vicentino” (VI)- (Garziere St. 42, 36014 Santorso VI) in the north of Italy. Both patients were followed for macular pucker in the surgical retina service of our unit since 2020. When ocular surgery became indicated, the procedure was scheduled and done; both during the same week of this year. Informed consensus from Italian Society of Ophthalmology was obtained and signed by each patient and all internal protocols were respected to ensure traceability and documentation for each visit and procedure.
Methods
The method of investigation for this study is a case report with critical literature review in the effort of interpretation for our findings. A micro incisional vitreo-retinal surgery (MIVS) with 3 standard 25 gauges sclerotomies was performed. Both patients’ retinas were stained for 30 seconds two times during the procedure with a vital dye, to highlight both epiretinal membrane and internal limiting membrane (ILM). A commercial sterile solution of Trypan Blue and Brilliant Blue G, solved in a physiologic phosphate buffer of sodium chloride, was used. Polyethylene glycol (PEG) was the support in this dye and lutein was also present. A comprehensive ocular examination was obtained in the pre-op assessment for both of our patients. Optical Coherence Tomography (OCT), Optical Coherence Tomography Angiography (OCT-A), Fluoresceine Angiography (FA), Indocianine Green Angiography (ICGA), blue Auto-Fluorescence (AF) and Multi Color images (MC) were also obtained using the Spectralis (Heidelberg Engineering Inc. - Franklin, USA). A complete full-field electroretinogram (ff-ERG) was done post-op in one patient. Immediately, when the adverse event was firstly hypothesized, the hospital committee was alerted. A formal report to the Italian pharmaceutical agency was also made, to let them investigate if impurities or contaminations were present into the pharmaceutical lot.
Results
Both patients were Caucasian, Patient 1 was a 70-year-old female, Patient 2 was an 83-year-old male. Pre-op best correct visual acuity (BCVA) was respectively 0.3 LogMAR in for patient 1 and 1.0 LogMAR for patient 2. Post-op follow-up immediately showed an inner retina inflammation (starting from the retinal nerve fiber layer), that progressively deepened in the external layers and progressively destroyed photoreceptors/retinal pigmented epithelium/ choriocapillaris. When external retina damage appeared, the OCT showed a sort of “crumbling” with multiple hyper-reflective spots and accumulation of drusen-like lipofuscin material, extended from posterior pole to nasal retina. In this scenario we observed complete parapapillary sparing in a circular area of about 700 microns. Both FA and ICGA showed a “salt and pepper” appearance with complete parapapillary sparing from the damage, AF and MC also confirmed this finding. In all exams we observed again a complete parapapillary preservation. The OCT-A too showed a circular parapapillary area of choriocapillaris sparing. After completing the surgical recovery, post-op BCVA was 1.6 LogMAR in both patients with many uncertainness and research, linked to the reported presence of a central scotoma. Furthermore, 2 months post-op, Patient 1 underwent a ff-ERG; this exam showed no abnormal responses from photoreceptors.
Conlusions
To investigate how the retina of our unfortunate patients was destroyed, we decided to perform many exams that all coherently showed sparing of the structure and function of parapapillary retina. This area, where the dye is mainly concentrated by gravity action during the procedure, appeared curiously preserved in both patients, in a really superimposable fashion. We don’t know if impurities or contaminations may have been present in our dyes, but in a pathogenic hypothesis the presence of a toxic light-activated compound in the external retina could have been present. The parapapillary sparing may represent an effect of a better choriocapillaris washout of toxic substances in this area, and the presence of a different vascular flow could be the reason. A similar mechanism may also be hypothesized in ABCA4-related diseases. Literature has shown in many case-reports how colorants can cause damage, mainly if they come in contact with the external retina, as it may happen during full thickness macular hole surgery. Further investigations may be needed to better understand the pathophysiology of the reported damage. Nevertheless, a lesson from this unlucky story may come out for many other ophthalmologists and patients.
Financial Disclosure
No finantial interests were present for eachone of the Authors
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