EyeWorld/ASCRS reporting live from AAO Refractive Subspecialty Day and the Cornea and Eye Banking Forum in San Francisco, Friday, October 11, 2019


EyeWorld/ASCRS reporting live from AAO Refractive Subspecialty Day and the Cornea and Eye Banking Forum in San Francisco, Friday, October 11, 2019
On Friday ahead of AAO, subspecialty day programming focused on refractive topics, among other things. The Cornea and Eye Banking Forum also took place.
Keynote lecture focuses on IOL power calculations
“Can we do better?” That’s what Douglas Koch, MD, Houston, sought to answer in his keynote lecture given at AAO’s Refractive Subspecialty Day.
When you look at the literature, 70–80% of outcomes are within 0.5 D of target, Dr. Koch said, noting that the best data uses the Hill-RBF formula, resulting in 90% within 0.5 D.
Sources of residual refractive error today, Dr. Koch said, are effective lens position (ELP) and the anterior and posterior cornea.
Dr. Koch said that it’s time to start talking about IOL calculation formulas in terms of how they work, rather than as generations. This would include geometric optics (Holladay 1, Hoffer-Q, SRK-T, Haigis, Barrett Universal 2, and Holladay 2), ray tracing (PhacoOptics [Olsen] and Okulix [Preussner]), artificial intelligence (Hill-RBF and Clarke), and combination formulas (Ladas Super formula and FullMonte IOL).
Ideally, ray tracing formulas would be the most accurate, because they incorporate all aberrations of the cornea and the IOL, but Dr. Koch said a major limitation is that they don’t provide a solution to the ELP quandary. Outcomes with ray tracing formulas to date are not better than other formulas.
OCT preoperatively and intraoperatively can improve ELP prediction, but Dr. Koch said there are no studies that show superior IOL calculation accuracy, and that’s because the ELP shifts unpredictably postoperatively.
“We may nail it on the operating room table, and it may change as the patient heals,” Dr. Koch said.
ELP prediction in short eyes is more challenging, because a high power IOL in a small anterior chamber means even a small shift creates a lot of refractive change. Conversely, long eyes, with the Wang-Koch modification, Barrett Universal 2, and Hill-RBF, are getting better results, in part, due to the low IOL power, Dr. Koch said. Post-LASIK eyes, he continued, still have room for improvement for IOL power calculation accuracy. When it comes to keratoconus, Dr. Koch cited research that shows the steeper the cornea, the greater the hyperopic error.
Corneal power continues to be a major source of error, Dr. Koch said, which is why it must be optimized. Other best practices for improving IOL calculation accuracy in 2019, according to Dr. Koch, include using accurate devices (optical or swept-source biometry and multizone LEDs for K readings), using the best formulas, and verifying quality of raw data used in calculations.

Editors’ note: Dr. Koch has relevant financial interests with Alcon, Carl Zeiss Meditec, Johnson & Johnson Vision, and Perfect Lens.

Keynote lecture on the pre-ectatic cornea
A second keynote lecture at Refractive Subspecialty Day was delivered by J. Bradley Randleman, MD, Cleveland. He discussed the progress, missteps, and next steps in identifying the pre-ectatic cornea.
First and foremost, he said there is a better understanding of corneal ectasia now than ever before, and it is identified at earlier stages than ever before. But accurate identification of this corneal condition “requires great training, technology, and effort on the part of the surgeon. There are no shortcuts,” Dr. Randleman said.
Major steps include corneal epithelial mapping, understanding corneal ectasia as a focally focal disease process, and understanding that corneal ectasia is, in part, inflammatory in nature. Epithelial thickness mapping combined with curvature, Dr. Randleman said, can be used to identify an ectatic cornea, on which surgery should be avoided. It also could rule-in a patient who might previously have been ruled out for refractive surgery.
In terms of being a focal disease process, Dr. Randleman cited research that shows pathology for keratoconus is primarily in the anterior third of the cornea. He also said when you compare the cone of a keratoconic cornea to a normal cornea with Brillouin microscopy, the cone is weaker, but the nonconical region is nearly identical in terms of biomechanics to the non-keratoconic cornea.
Dr. Randleman also described research that identified corneal ectasias as an inflammatory mediated process, with a reduction in lysyl oxidase levels (primarily in focal areas) and higher TGF-beta levels.
In terms of missteps in identifying pre-ectatic corneas, Dr. Randleman said there has been an overemphasis on machine-derived metrics, an overemphasis on the relative value of the posterior cornea, and an overreliance on current biomechanical measures.
Screening today should include multiple complimentary technologies and surgeons should use all the data available, not just rely primarily on metrics. All corneal surfaces should be evaluated, Dr. Randleman said.
Possible enhanced screening measures in the pipeline include genetic testing, point-of-care inflammatory evaluation, and direct focal biomechanical measurements.

Editors’ note: Dr. Randleman does not have financial interests related to his comments.

Considering medical treatment for presbyopia

There are 30–40 million presbyopic patients in the U.S., and while there are a number of surgical presbyopia-correcting procedures, as Sheri Rowen, MD, Newport Beach, California, noted, they are invasive and difficult to reverse or correct, if needed. While there is no FDA-approved pharmaceutical option for presbyopia, Dr. Rowen discussed a range of upcoming, topical treatments.
The products in the pipeline operate based on two modes of action: 1) working directly to improve accommodation of the lens itself (which has been stiffened with age) and 2) increasing depth of field through a pinhole effect.
UNR844 (Novartis, previously EVO6) creates hydrolysis of proteins in the stiffened lens, allowing free flow of cytosol centrally to restore accommodation. Dr. Rowen said research in a mouse model resulted in a 40% more elastic lens after 5 weeks of drug application compared to the contralateral eye without the drug. A Phase 2 study for UNR844 is forthcoming.
Miotic pharmaceutical options, Dr. Rowen said, need to be comfortable for the patient, long-lasting, allow for depth of field without loss of night visual acuity, have an excellent safety profile, and maintain distance vision. Allergan has completed Phase 2b studies with Phase 3 initiated for a once-daily drop, showing improved near visual acuity for hours, fast onset of action, and tolerability. Other products being studied that work by inducing a miotic effect include Liquid Vision (Presbyopia Therapies) and CSF-1 (Orasis), which has completed a Phase 2b study.

Editors’ note: Dr. Rowen has relevant financial interests with Allergan, Alcon, Bausch + Lomb, Johnson & Johnson Vision, Orasis, Novartis, and Shire.

DSAEK failure in eyes with pre-existing glaucoma
During the Cornea and Eye Banking Forum, Jennifer Li, MD, Sacramento, California, highlighted a study on DSAEK failure in eyes with pre-existing glaucoma.
DSAEK has become the most common form of corneal transplantation. “We do know, of course, that glaucoma can be linked to endothelial keratoplasty failure,” she added.
The study was a retrospective chart review of all DSAEK cases by a single surgeon from 2012–2018. The primary endpoint was graft failure, with secondary endpoint of graft dislocation.
Data collected included preoperative demographics, pre/post IOP, surgical indication, BCVA, failures, glaucoma diagnosis, glaucoma surgery, glaucoma medications, and re-bubbling.
Dr. Li noted that 241 eyes of 176 patients met inclusion criteria. This included 116 eyes with glaucoma.
Fuchs’ was the primary indication for DSAEK, Dr. Li said. Of all the eyes included in the study, 41 (17%) experienced graft failure. The failure rate for eyes with no history of glaucoma was 2.4% and 32.8% in eyes with a history of glaucoma. Dr. Li said grafts tended to fail earlier in patients with glaucoma.
Any glaucoma surgery increases risk of failure, she said, and for patients with more than one prior glaucoma surgery, the risk becomes even greater. Glaucoma drainage devices are one of the biggest factors for DSAEK failures, she said.
Though the failure rate based on the number of IOP-lowering medications was not statistically significant, Dr. Li said that patients are generally less likely to have a graft failure when on fewer medications. Many medication subtypes incur risks on DSAEK failures, she said, and use of a topical beta blocker was statistically significant. Dr. Li also noted hypotony as a factor in graft failure and increased need for re-bubbling.
Limitations of this study were that it was a retrospective and there were multiple potential confounders.
In conclusion, Dr. Li stressed the risk of DSAEK failure with glaucoma and the potential for worse outcomes with beta blockers, use of multiple medications, and hypotony. She also added that POAG, CACG, and JOAG may be worse than other subtypes of glaucoma.

Editors’ note: Dr. Li has no relevant financial interests.

Management of Limbal Stem Cell Deficiency and Corneal Stromal Opacification
The first mini-symposium at the Cornea and Eye Banking Forum focused on limbal stem cell deficiency (LSCD) and corneal stromal opacification, with presenters highlighting LSCD, autologous limbal stem cell transplantation, repair of corneal injuries using bioadhesive hydrogels, and cultivated human corneal keratocytes for corneal opacities.
Sophie Deng, MD, PhD, Los Angeles, led with LSCD discussion. It has been described as “an ocular surface disease caused by a decrease in the population and/or function of corneal epithelial stem/progenitor cells.” This decrease leads to the inability to sustain the normal homeostasis of the corneal epithelium, she said. LSCD may be acquired or hereditary, and diagnosis is based on clinical presentation (symptoms and signs). However, the signs of an abnormal epithelium can be subtle and often not specific to LSCD, Dr. Deng said, adding that adjunct diagnostic tests may be necessary.
Also during the session, Nasim Annabi, PhD, Los Angeles, discussed repair of corneal injuries using bioadhesive hydrogels, specifically highlighting a product called GelCORE.
Corneal stroma defects may be caused by physical trauma, burns, inflammation, or infections/corneal ulcers, she said. The standard of care to handle these include cyanoacrylate glue, suturing, or tissue patch grafting/therapeutic corneal grafting, but all of these have significant disadvantages, such as high costs, uncontrolled tissue healing, and risk of immune response (in case of grafts), Dr. Annabi said.
She went on to describe GelCORE as made from gelatin-based, photocrosslinkable biomaterials that is more adhesive than commercially available sealants. Dr. Annabi added that GelCORE is easy to apply with tunable biomechanical properties, a tunable retention period by varying polymer ratios, strong adhesion, and the potential for use as drug delivery platform.

Editors’ note: The speakers have no relevant financial interests.

Management of Corneal Endothelial Dysfunction: Where Are We Heading?
The second mini-symposium of the Cornea and Eye Banking Forum looked at options in the management of corneal endothelial dysfunction.
Ula Jurkunas, MD, Boston, discussed genetic modulation. The corneal endothelium, with aging and time, is disrupted by guttae, she said.
Fuchs’ is a late-onset genetic disorder, and there are many ways to study the genetics of it, she said.
The most common and relevant gene is TCF4 repeat expansion. Dr. Jurkunas said there are studies underway to understand how TCF4 repeat expansion can be treated, and she noted that one way is to excise those repeats.
Dr. Jurkunas went on to discuss CRISPR-Cas9, which uses a viral vector to perform gene editing in vivo. She noted that there is currently no work with this in cornea underway, however, it has been experimented with in retinal degenerations. Alternatively, instead of packaging CRISPR-Cas9 into a viral particle, you could put it into a nanoparticle, Dr. Jurkunas said.
She also mentioned using an antisense oligonucleotide (ASO), but she noted that this is in a “lab stage” and not in trials.
Dr. Jurkunas offered several key points to consider when designing genetic therapies. First, she said to consider the role of guttae and variation in topographical distribution. Secondly, she said it’s important to consider the interplay between gene and environment and suggested targeting modifiable factors. Lastly, she pointed to lessons learned from Descemet stripping only: not all cells manifest the disease; peripheral cells may be a source of healthy cells; think more about cell migration and proliferation; and know the role of corneal endothelial progenitor cells.

Editors’ note: Dr. Jurkunas has relevant financial interests with Intellia.

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Medical editors: Eric Donnenfeld, MD, chief medical editor; Rosa Braga-Mele, MD, cataract editor; Clara Chan, MD, cornea editor; Nathan Radcliffe, MD, glaucoma editor; Vance Thompson, MD, refractive editor

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