Investigators note a supply shortage led to use of half a dose for imaging purposes.
Reviewed by Andrei-Alexandru Szigiato, MD
Clinicians can safely and effectively use half a dose, rather than the standard full dose, of fluorescein when conducting ultrawidefield fluorescein angiography (UWFA) to image the retina to look for retinal vascular disease, according to research presented at the Canadian Ophthalmological Society Annual Meeting. The impetus for using half a dose instead of a full dose stems from a clinical situation in which there was a lack of availability of fluorescein to provide the full dose, necessitating the rationing of fluorescein for imaging purposes, explained presenter Andrei-Alexandru Szigiato, MD, a medical retina fellow in the Department of Ophthalmology at the Cole Eye Institute at Cleveland Clinic in Ohio.
“There was a nationwide shortage in the [United States] of fluorescein in 2022,” said Szigiato, a presenting author. “In order to provide fluorescein angiograms for all patients [who] needed them, such as patients with uveitis and diabetes mellitus, the Cole Eye Institute switched to using [half a dose of fluorescein].”
Clinicians initially did not notice any difference in the clinical utility of the images generated with the reduced dose of 250 mg of fluorescein compared with the standard full dose of 500 mg, but they wanted to rigorously review the images and see whether there were observable differences, according to Szigiato. “We decided to formally assess image quality and leakage, both qualitatively and quantitatively, using a machine learning algorithm,” Szigiato said in the interview.
Szigiato and coinvestigators included adult patients who had received both half- and full-dose UWFA with the Optos California imaging system at the Cole Eye Institute. They excluded from this retrospective review eyes that had undergone intraocular injections, laser procedures, recent immunosuppression, and worsened or improved uveitis.
Moreover, with coinvestigators, Szigiato reviewed late-phase UWFA images, comparing automated scores of those captured with use of half a dose vs a full dose of fluorescein. In terms of qualitative assessment of image quality and relative vascular leakage, it was performed by 2 blinded independent reviewers.
The review included 56 eyes of 39 patients; most (43% or 77%) were uveitic. Diabetes was the second most common condition with 5 eyes or 9% being diabetic and the balance of eyes having other diagnoses. There were no changes in visual acuity, nor in anterior chamber cell and vitreous cell between UWFA using a full dose and UWFA using half a dose.
Investigators did find, with use of automated segmentation analysis, a statistically significant difference in signs of mildly elevated vascular leakage in half-dose images vs full-dose images: 8.4 ± 2.3% vs 7.5 ± 1.7%; P = .02. Szigiato and coinvestigators attributed this to a higher background signal in cases where exposure times were increased due to media opacity.
The blinded reviewers observed similar image quality, similar leakage (diffusion of the dye) in the macula, and similar leakage in both the midperiphery and periphery with half-dose and full-dose images. “We did not observe a consistent difference in the quality of the images, although half-dose images did tend to have a brighter background, likely due to higher exposure times in patients with media opacity,” Szigiato said.
Adverse events were similar when patients were exposed to a full dose of fluorescein vs half a dose. Investigators found 3 cases of nausea when patients were exposed to half a dose of fluorescein and 2 instances of nausea when patients were exposed to a full dose. There was 1 case of urticaria when a patient was exposed to a full dose.
“We did find the rates of nausea were similar and infrequent,” Szigiato explained. “However, we were underpowered to detect small differences [in adverse events] between use of a half dose and a full dose.” Another study that compared use of full-dose and half-dose fluorescein angiography in visualization of retinal structures also found few adverse events, with those adverse events being nausea and urticaria.1
Other concerns in terms of possible adverse events are allergic reactions. Although rare, there is the potential for a patient to have an allergy to the fluorescein dye, Szigiato explained. If images can be obtained without sacrificing quality and accuracy, it is preferable in some patient populations, such as those with renal impairment, to decrease the use of dye and use half a dose of fluorescein with UWFA.
Concerns around the carbon footprint associated with eye care in general and UWFA have been raised in the medical literature. In view of these concerns, the use of half a dose of fluorescein to perform UWFA would be more environmentally friendly, Szigiato noted. “There would be less waste with the use of the half dose of fluorescein instead of the full dose,” he said.