New research published in the Journal of Cataract & Refractive Surgery explores Johns Hopkins University investigators’ development of an ophthalmic viscosurgical device (OVD) composed of fluorescein-conjugated hyaluronic acid (HA; conjHA) for cataract surgery.
To put it plainly: They’ve created a novel color-changing hydrogel to assist surgeons in verifying complete removal of the eye’s lens following surgery.
Let’s start with some background.
Cataract surgery traditionally involves an ophthalmic surgeon removing and replacing a patient’s cloudy lens with an artificial lens.
- Key to this process: The use of OVD hydrogels (via injection) to maintain pressure within the anterior chamber (AC) while also keeping the eye inflated and providing protection of the corneal endothelium.
The issue: An OVD needs to be removed following surgery via irrigation/aspiration (I/A); if it’s not—and there’s leftover gel—it may prevent ocular fluid drainage through the trabecular meshwork (TM) and, as a result, lead to increased intraocular pressure (IOP) post-op.
- To note: Aside from this IOP increase, which could cause optic nerve trauma, an OVD’s retention may also cause corneal edema and patient discomfort
So what challenges are associated with OVDs?
During surgery: Surgeons have difficulty with OVD visualization, as most commercially-available devices are “clear hydrogels that can only be visualized intraocularly,” researchers noted.
And after surgery: Because of OVDs’ clear appearance, removing them at the conclusion of cataract surgery poses a significant challenge (as any leftover gel may
And before you ask: No, an OVD can’t be opaque either, as “it is necessary … to be clear during phacoemulsification and IOL insertion (in order) to enable visualization of ocular structures,” according to investigators.
Gotcha. So what makes these devices translucent?
A key ingredient that harkens back to 1983 when the FDA approved the first OVD (Healon).
That component: Sodium hyaluronate (also known as hyaluronic acid [HA])
- Even after 40+ years, this reportedly remains the “polymer of choice” for the majority of OVDs currently on the market.
Following Healon's approval, later versions of OVD incorporated tints of fluorescein sodium (Healon Yellow; still difficult for visualization) as well as blue-light microscopy (dubbed “fluorescent viscoelastic enhancement [FV]), among other alternative solutions.
But the problem: These tints (staining agents; dyes) would leak out of the gel and spread into the eye, making it difficult for surgeons to ascertain between surgical gel and dispersed dye.
Interesting ... so how does this fluorescein-conjHA come into play?
This is yet another (albeit, more promising) alternative solution.
Investigators in this research used fluorescein-conjHA (originally developed in 1975) to engineer a clear gel that glows “fluorescent” green when placed under blue light.
How it works: This gel chemically bonds the fluorescent dye to the polymer that forms the gel, ensuring it remains intact throughout surgery, without leaking into the eye.
What was the hypothesis?
Fluorescence could be used for “conditional visualization of OVD” during and after cataract surgery; the OVD is mainly clear during the majority of the surgery when under white light and is also “clearly visualized when illuminated at the proper excitation wavelength when desired.”
- The goal: For surgeons to “ensure complete OVD removal,” while dodging any potential risk for I/A.
And how was this tested?
First: Varying ratios of both conjHA and unconjugated HA (unconjHA) were combined to develop conjOVD with a varied fluorescence intensity.
Next: This conjHA: unconjHA ratio was used to maximize the visible clarity under white light (WL) as well as the fluorescence intensity under cobalt blue light (CBL), thus enabling conditional visualization for a surgeon.
- To note: Investigators assessed the effect of this via rotational rheometry.
Then: They immersed three IOLs—hydrophobic acrylic, PMMA, and hydrophilic acrylic—in conjOVD viscosity (10% concentration) for 4 hours in order to determine IOL staining.
Was this studied in an ex vivo or in vivo model?
One of the two! After that testing, the researchers conducted an ex vivo clinical trial by using porcine (pig) eyes illuminated with WL or CBL under a surgical microscope.
See the details of that process, including the injection and removal of 5% conjOVD.
And what were the findings?
To start, the researchers reported success in producing conjOVD with increasing fluorescence.
- In fact, when under CBL illumination, both 5% and 10% conjOVD fluorescence were notably intense—although visualization was still possible.
For a closer look at the effect of fluorescein conjugation on the material properties of the OVD that was procured, click here (hint: only a subtle increase in OVD viscosity was observed).
How did those submerged IOLs fare?
After their removal from the OVD and a rinse with a balanced salt solution, the IOLs did not exhibit any fluorescence. The investigators noted that images under CBL were comparable with naïve IOLs.
Translation: The fluorescein-conjugated OVD did not prevent IOL clarity.
And in this ex vivo model?
When placed under WL, the pig eye’s 5% conjOVD-injected AC remained clear.
Meanwhile, the iris adopted a slight yellow hue that later resolved after the conjOVD was removed via I/A, according to investigators.
The conclusion: When sufficiently irrigated, fluorescence can’t be visualized on IOLs. Thus, “we do not anticipate IOL staining will affect the progress of surgery using conjOVD,” the study authors stated.
And how was visualization under CBL?
When injected into the pig eyes, “5% conjOVD exhibited striking fluorescence under CBL.”
The study authors added that fluorescein conjugation also enabled visualization of the OVD during removal via I/A—including residual OVD—leading to a decrease in severity and potential occurrence of increased IOP postop.
- While this is promising, a few limitations from this study should also be considered.
Interesting … so what’s the takeaway from this?
The authors noted that, in a clinical workflow, “surgeons would be able to perform operations as normal under WL and then use CBL to visualize conjOVD during removal.
However, they also noted that this gel’s efficacy and safety still needs to be tested for its safety and efficacy in human trials to determine its true potential to be incorporated into standard ophthalmic practice.