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A visual simulator (SimVisGekko, 2EyesVision) helps patients to choose how well multifocal IOLs function before surgical implantation and improve satisfaction with surgical outcomes.

) that provides patients the experience of vision with multifocal IOLs (mIOLs) before actual implantation may help to manage patient expectations, according to Susana Marcos, PhD.

This innovation arose out of the scaling down of technologies that originated in astronomy, i.e., adaptive optics, into a system useful to ophthalmologists for prescribing correction for presbyopia and simulating mIOLs.

Despite the availability of mIOLs, only 7% of patients opt for this correction modality after cataract surgery, noted Dr. Marcos, research professor, Instituto de Optica Daza de ValdÃ©s, Consejo Superior de Investigaciones CientÃ­ficas, Madrid.

The challenge may be the difficulty with explaining multifocality to patients.

In addition, it is difficult for patients to decide about mIOL implantation if they cannot visualize what their vision will be preoperatively, a scenario that leaves them with uncertainty about both their expectations and the actual surgical results.

A solution to this may be use of the mobile visual simulator that would ease their decision-making process.

“Visual simulators will help to sell more premium lenses and screen out prospective unhappy patients,” Dr. Marcos said. “This technology would be valuable for patients, clinicians, and IOL manufacturers.”

The device provides practical utility in the clinic, in that it improves patient satisfaction, facilitates comparison of corrective solutions, and saves time by providing an easy explanation of multifocality. It also provides business advantages by reducing patient complaints and refunds, provides a competitive advantage to doctors who adopt the device early, and increases the number of mIOL prescriptions.

Advanced toric IOL calculator improves refractive outcomes

The wearable, binocular, see-through device provides a 20-degree field of view, is programmable on a tablet, and simulates multifocal and extended-depth-of focus corrections and provides monovision or modified monovision correction.

“This facilitates testing a range of preoperative corrections,” she said.

The device contains optotunable lenses. Using a custom, high-speed electronic driver, the lenses can change focus rapidly by a process called temporal multiplexing.

“With periodic variations of the optical power at high speed, above 50 Hz, the static appearance of multifocal retinal images is provided by mapping spatial distribution in a lens into temporal distribution in the optotunable lens,” Dr. Marcos said.

She described this in a trifocal FineVision IOL. The map in the IOL is defined with a set of coefficients; the data show how much time the lens spends at the different power additions. With a trifocal lens the coefficients are at three different foci. This process can be performed with different coefficients and simulate extended-depth-of-focus lens types and different energy distributions.

“We also control for dynamic effects in the lens so that we can really map the true focus performance of the lens,” she said.

A comparison of the performance of an actual commercial IOL with the simulation showed how well the images of the two matched.

Performance of trifocal toric IOL highlighted in tests

When the mobile visual simulator was taken into the clinic, it performed well.

“We found that the device replicates mIOLs,” Dr. Marcos said. “We performed the test with a trifocal IOL in the SimVis preoperatively and the patient was ultimately implanted with the lens. We found that in patients with clear lenses and those with cataracts, the preoperative (with SimVis) and postoperative (with the implanted mIOL) defocus curved matched.”

In the presence of a cataract, there is a shift down because of the light distribution caused by the cataract, but the shape of the defocus focus curve is well captured, according to Dr. Marcos.

This technology is also useful for patients opting for multifocal contact lenses. An excellence replication of the contact lens performance on eye  was achieved with the SimVis simulation. For different lens designs with different power additions.

The device also was tested using different natural images at far and near distances under conditions during the day and at night.

When tested in a patient with corrected binocular far vision, for example, the scores at the far distance were high and the scores for near were low. When bilateral bifocal correction was provided the far vision decreased slightly and the near vision improved. This also can be applied to monovision and modified monovision.

When the patient is tested with different corrective options, surgery can proceed with much more certainty regarding the postoperative vision, Dr. Marcos noted.

The physician can choose the desired lenses and control the test on an iPad. The management of the mobile device allows connection of every iPad to the cloud, remote management of the devices, security management, remote app updates, monitoring and tracking, and remote troubleshooting.

Striving for perfection: Creating the perfect IOL

In addition, when new IOL designs become available the software is updated.

“This technology provides a powerful back-end,” Dr. Marcos said. “Over and above monitoring the use of the SimVis, we can monitor different patient lens preferences, the rates of actual implantations of those IOLs, and the conversion rate to multifocality.”

This is powerful information that is enabled by the fact that we can perform this preoperative clinical testing before surgery, she emphasized.

“We believe that SimVis represents a new paradigm in presbyopia correction that provides patient education, aid in lens selection, reduced uncertainty preoperatively, virtual clinical trials, the ability to test multiple lenses, and large data sets of patient preferences and usage,” Dr. Marcos concluded.

Innovative IOL power calculations gain accuracy

Susana Marcos, PhD
	E: susana@io.cfmac.csic.es
	Dr. Marcos is coinventor of the SimVis technology and co-founder and shareholder in 2EyesVision.

Articles

Simulator helps patients ‘see’ with multifocal IOLs before implantation

Female ophthalmology residents performed both significantly (p < 0.001) fewer cataract surgeries and fewer total procedures (p < 0.001) compared with the male residents from 2005 to 2017.

There is no argument with the old adage “practice makes perfect.” This is especially true for ophthalmology residents. The results of studies both older and more recent all point in the same direction: operating room performance by ophthalmology residents improves with increasing numbers of surgeries.

However, a recent study found a highly noteworthy finding, i.e., that female residents performed significantly fewer 

 and significantly fewer total numbers of procedures compared with the male residents from 2005 to 2017 (p < 0.001 for both comparisons).

And this is despite that fact that the numbers of male and female residents were similar in ophthalmology training programs.

This raises the questions: While the numbers of men and women in the residency training programs were similar, was the surgical experience the same?

This finding emerged from a retrospective longitudinal analysis of recent case logs performed by Dan Gong, MD, and colleagues. The authors reported their findings in in 

9 best practices in refractive-cataract surgery planning

All 119 ophthalmology residency programs in the United States were asked to participate. Participation was anonymous, and according to study authors, the following data were collected for each graduating resident:

number of cataract procedures performed as the primary surgeon,

total number of procedures performed, and

The main outcome measures were the mean volumes of cataract surgeries and total procedures, resident gender, and maternity or paternity leave.

Of the programs contacted, 24 (20.2%) residency programs provided data on 1,271 residents, of which 815 (64.1%) were men and 456 were women (35.9%) who graduated from 2005 to 2017.

The authors reported that the male residents performed more cataract surgeries than the female residents (mean, 176.7 versus 161.7, respectively); the male residents also performed a higher mean number of total procedures (509.4 versus 451.3, respectively). Eighty-five male residents and 71 female residents took parental leave.

Interestingly, the male residents who took parental leave performed a mean of 27.5 more cataract surgeries compared with the men who did not take parental leave, the female residents who took parental leave performed a similar number of surgeries to those who did not take parental leave.

Beginning in 2005, each subsequent year saw an increase in the number of cataract surgeries performed by each resident, although there was no significant (p = 0.11) gender difference identified.

However, there was a significant (p = 0.008) gender difference in the total volume of procedures performed; over time, the male residents performed more surgeries than the female residents and that gap widened over time.

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The differences in the numbers of cataract surgeries performed by the female residents compared with the male residents ranged from 7.8 to 22.2 fewer, and the differences in the total numbers of procedures performed by the female residents ranged from 36.0 to 80.2 fewer.

The numbers of cataract surgeries performed by the male and female residents, however, more than met the requirements of the Accreditation Council for Graduate Medical Education, the authors pointed out.

The growing gap in the total number of procedures over time was of special interest to the study investigators.

They commented, “One concerning trend that deserves special mention is the growing gap in total procedural volume between male and female residents as time progresses. Although we are encouraged that [the] overall case volume increased from 2005 to 2017, it is unclear why the increase asymmetrically affects male and female residents.”

The parental leave was found not to affect the total numbers of procedures performed by the male and female residents.

The authors suggested that “if residents are more likely to take parental leave in their third year, taking leave would have less of an effect on procedural volume during the first and second years of residency when many laser and other procedures are performed.”

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The investigators recommended that each residency program director evaluate the case volumes of the male and female residents and if there were differences found the directors should examine if the policies of the programs differ for men and women. Some considerations could include the manner in which a program helps residents with their case volume when taking parental leave, adjusting rotation schedules based on the timing of the parental leave to minimize the disruptive effect on the residents’ education, and determining how and when the attendings pass on surgical cases to the residents.

The authors suggested that further studies with more participating residency programs be undertaken to confirm the current study data.

The authors concluded, “Female residents performed 7.8 to 22.2 fewer cataract operations and 36.0 to 80.2 fewer total procedures compared with their male counterparts from 2005 to 2017, a finding that warrants further exploration to ensure that residents have equivalent surgical training experiences during residency regardless of gender.”

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Cataract surgical experiences of residents: Exploring gender differences

Glaucoma medication compliance in an inpatient setting is poor, with more than one-third of patients not receiving their anti-glaucoma drugs.

Ironically, though IOP drugs are markedly effective at decreasing the development and progression of open-angle 

, compliance is “notoriously poor” among aging patients for a few reasons, said 

Among the factors are reliance on staff in nursing homes and subacute rehabilitation centers as well as transfer of care from inpatient hospitals, according to Dr. Nanda, from the 

 of Columbia University Irving Medical Center and 

About 2.2 million U.S. adults have glaucoma, and by as early as next year that number is expected to increase unbelievably to 3.36 million.

“Medication reconciliation is the process by which a patient’s outpatient medication regimen is documented and converted to synonymous medications in the hospital formulary. The intention of this process is to continue all outpatient medications during a patient’s hospital stay, unless otherwise contraindicated,” the authors explained.

However, while this process is primarily an electronic one, “…medication reconciliation on hospital admission and discharge is fraught with discrepancies, with errors occurring as often as 70% to 85% of the time,” they noted and explained that the frequency of these error rates associated with anti-glaucoma medications is unknown.

In addition, glaucoma is not considered to be as important as other chronic conditions such as 

. The authors theorized that reconciliation of glaucoma drugs is suboptimal in inpatient hospitals, resulting in noncompliance.

EHR-linked glaucoma medication reminder may improve adherence

In light of this, they conducted a retrospective, cross-sectional, hospital-based study that included 475 patients (46.3% women; average age, 80.2 years) who had been admitted to a general medicine regional hospital service (average stay, 4.61 ± 3.7 days).

The investigators reviewed the administrative database and cross-referenced patient charts and the following information was collected: demographic data, past medical problems, inpatient orders, intake history and physical, length of stay, and admitting diagnosis.

The main outcome measures were twofold: the effect of outpatient glaucoma drop reconciliation and recognition of glaucoma as a pertinent past medical problem in a patient’s intake history and physical on inpatient eye-drop administration, they recounted.

Analysis of the database and charts found that “in total, 63.8% achieved successful reconciliation of medication on the hospital floor, resulting in a 36.2% eye-drop abstinence rate during the hospital stay,” the authors reported. 

Regarding this, the investigators commented that while the reconciliation occurred, successful administration did not necessarily occur because the practitioners had to convert each reconciled medication intentionally to an active inpatient order.

Of 386 (81.3%) patients who had successful reconciliation of their anti-glaucoma medications, these patients achieved significantly different rates of eye-drop administration, i.e., 283 (73.3%) of the 386 patients received anti-glaucoma medications on the floor compared with 19 (21.0%) of 89 patients without successful reconciliation who received their medications, a difference that reached significance (

Another important finding was that the presence of glaucoma was recognized in the history and physical in less than half of patients, 42.5%.

“Recognition of glaucoma as a pertinent medical problem was poor,” the investigators commented, “with only 202 of 475 (42.5%) patients having glaucoma listed in their intake history and physical. Among those with glaucoma listed, 153 of 202 patients (75.7%) received glaucoma medications. In comparison, in those without glaucoma listed (150/273), 55.0% received glaucoma medications (

Pharmacologic pipeline makes waves in glaucoma

The study emphasized the importance of accurate recording of the patients’ medication regimen before admission to a hospital in order to improve eye-drop administration. This could be improved, they suggested, by using teaching rounds or morning case presentations as opportunities for residents and staff to become familiar with the various types of anti-glaucoma drops and administration regimens that are frequently prescribed.

“This ideally would include a table or chart providing the generic medications that are available in the hospital formulary and their synonyms in the outpatient setting. It is imperative that these teachings also emphasize the chronic nature of this disease and the vision-threatening consequences of prolonged noncompliance,” the authors stated.

They also suggested that small cards listing basic medication information, such as the name, dose, side effects, and regimen, be provided with the goal of improving quality as well as serving as a reminder to inquire about glaucoma as a patient’s chronic medical problem.

The study concluded, “Glaucoma treatment incurs a high rate of medication noncompliance, especially in the elderly. The present study demonstrates that more than one third of patients admitted to an academic medical center do not receive their glaucoma medications. Patients discharged to nursing homes, subacute rehabilitation, and assisted living facilities rely on appropriate discharge medication reconciliations, resulting in forced abstinence during transition of care. An emphasis on appropriate medical reconciliation and recognition of glaucoma as a pertinent past medical problem will improve rates of eye-drop administration on inpatient admission significantly.”

Glaucoma medication compliance in inpatient settings: The Holy Grail

Investigators reported an important first step in a treatment approach for advanced dry age-related macular degeneration (AMD), which has until now had few options for millions of affected patients around the world.

The study showed that the California Project to Cure Blindness Retinal Pigment Epithelium (CPCB-RPE1, Regenerative Patch Technologies), a subretinal implant containing allogeneic human embryonic stem cell-derived retinal pigment epithelium (RPE) cells, was safe and well-tolerated by patients with this type of AMD.

Amir H. Kashani, MD, PhD, lead author of the study, principal investigator of the clinical trial at the University of Southern California, and currently an associate professor of ophthalmology at the Wilmer Eye Institute, Johns Hopkins University, Baltimore, reported results at the Bascom Palmer Eye Institute’s 19th annual Angiogenesis, Exudation, and Degeneration 2022 Virtual Edition conference.

The primary end-point was the safety of this approach at 1 year after implantation. Patients with dry AMD and severe vision loss secondary to geographic atrophy (GA) were included. The implant was delivered into the subretinal space of the worse-seeing eye of 15 patients using a custom subretinal insertion device in an outpatient surgery setting.

The median age of the 15 patients (9 women, 6 men) was 78 years (range, 69-85). The patients were all legally blind in the treated eye (best-corrected visual acuity [BCVA] ≤ 20/200). The patientswere divided into 2 cohorts: cohort 1 included 6 patients and cohort 2 had 9 patients.

All patients were evaluated postoperatively using optical coherence tomography and fundus photography. The implants remained pigmented and did not migrate postoperatively.

The investigators reported that no unexpected serious adverse events occurred in any study patients. Expected serious ocular adverse events did occur in cohort 1 subjects, i.e., retinal hemorrhage, edema, focal retinal detachment, or RPE detachment. Changes to the intraoperative procedure to improve hemostasis were implemented in cohort 2 subjects and prevented any serious ocular events in the second cohort.

No inflammation developed in any patient that was suggestive of an immune response directed toward the donor implant.

“It is encouraging that even though these implanted cells were not HLA-matched, there were no clinical signs of retinitis, vitritis, vasculitis, or choroiditis even in the absence of long-term immunosuppression in the phase 1/2a study,” Kashani said.

Although the study was not powered to detect efficacy, the BCVA improved in 4 treated eyes by more than 5 letters of vision (range, 6 to 13 letters). More treated eyes (27%) had a nonsignificant gain in vision of more than 5 letters compared to the untreated eye (7%) respectively. Conversely, more untreated eyes (47% vs 33%) lost 5 or more letters, a difference that did not reach significance.

One of the patients died of natural causes 2 years after the CPCB-RPE1 was implanted. The death was unrelated to this research. Both eyes were enucleated and analyzed histopathologically. The postmortem studies showed the presence of donor RPE cells 2 years after implantation by immunoreactivity for RPE65 and donor-specific HLA Class I molecules.Additional markers of RPE cell polarity and phagocytosis suggest that the donor RPE cells were functioning.

The authors speculated that the mechanism of action for the CPCB-RPE1 is the result of enhanced viability of surviving photoreceptor cells in the retina directly overlying or adjacent to the CPCB-RPE1 implant. However, they noted the need for additional data. They also theorized that dormant photoreceptors in the area of the GA may have been rehabilitated by the CPCB-RPE1 implant and stimulated to form outer segments.

Based on these results, they concluded that the implant procedure is feasible on an outpatient basis and that the implant was safe and well-tolerated in this patient population.

Kashani JS, Lebkowski JS, Rahhal FM, et al. One-year follow-up in a phase 1/2a clinical trial of an allogeneic RPE cell bioengineered implant for advanced dry age-related macular degeneration. TVST 2021;10(10):13; https://doi.org10.1167/tvst,10.10.13

In a presentation at the Bascom Palmer Eye Institute’s 19th annual Angiogenesis, Exudation, and Degeneration 2022 Virtual Edition, Amir Kashani, MD, PhD, discussed results that show the implant procedure is feasible on an outpatient basis and has a good safety and efficacy profile. 

Study finds subretinal implant for advanced dry AMD is safe, well-tolerated

 suggest that SARS-CoV-2 may diffuse from the ocular surfaces to the patient’s body, and use of a conjunctival swab may be another method of diagnosing the virus, according to Claudio Azzolini, MD, from the Unit of Ophthalmology, Azienda Socio-Sanitaria Territoriale (ASST) dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy,

Azzolini and colleagues investigated the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detected in the tears of patients with COVID-19 based on the hypothesis that bodily fluids may serve as the conduits of viral spread, although thus far “insufficient information is available on the presence of the virus in human tears,” they pointed out.

The investigators used real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) to detect the virus in the tear samples from 91 patients in 2 intensive care units in northern Italy, between April 9 and May 5, 2020. 

COVID-19 had been clinically diagnosed using rRT-PCR performed on nasopharyngeal swabs and by radiology studies of these patients. 

Seventeen healthy volunteers who provided conjunctival swabs served as controls. The mean age of the 108 study participants was 58.7 years (55 women).

“SARS-CoV-2 was found on the ocular surface in 52 of 91 patients with COVID-19 (57.1%; 95% CI, 46.3%-67.5%), with a wide variability in the mean viral load from both eyes,” the investigators said.

They also evaluated a subset of 41 patients who had nasopharyngeal and conjunctival swabs performed on the same day or within 2 days and reported a “concordance of 63.0% (95% CI, 41.0%-81.0%) was found between positive conjunctival and nasopharyngeal swab test results when performed within 2 days of each other.”

Seven of 17 patients (41.2%; 95% CI, 18.0%-67.0%) in the subset had negative conjunctival and nasopharyngeal swabs, and the other 10 of these patients had negative nasopharyngeal swabs but positive conjunctival swabs.

This study showed that SARS-CoV-2 RNA was on the ocular surface in more than half of the patients in the COVID-19 cohort. 

“Because patients may have positive test results with a conjunctival swab and negative results with a nasopharyngeal swab, use of the slightly invasive conjunctival swab may be considered as a supplementary diagnostic test,” the investigators advised.



1. Azzolini C, Donati S, Premi E, et al. SARS-CoV-2 on ocular surfaces in a cohort of patients with COVID-19 from the Lombardy Region, Italy. JAMA Ophthalmol. Published online March 4, 2021. doi:10.1001/jamaophthalmol.2020.5464

Investigators suggest that SARS-CoV-2 may diffuse from the ocular surfaces to the patient’s body, and use of a conjunctival swab may be another method of diagnosing the virus.

SARS-CoV-2 populates ocular surfaces in COVID-19 patients in Northern Italy



This article was reviewed by Justine S. Paradis, PhD



The results of a preclinical study indicate there is hope for an effective treatment for the GNAQ-driven metastatic uveal melanoma, an aggressive form of the disease.

The treatment relies on 2 components, the MEK inhibitor trametinib or the second generation RAF/MEK inhibitor VS-6766 (Verastem Oncology) combined with defactinib, a focal adhesion kinase (FAK) inhibitor (Verastem Oncology), that work better together than apart for controlling uveal melanoma.



Light-activated agent novel option for uveal melanoma 

The importance of this potential treatment is underscored by the fact that uveal melanoma is the most frequently occurring ocular cancer in adults, and it becomes metastatic in 50% of patients in whom it develops. The survival rate currently is 2 years, with only 8% surviving following metastasis to the liver.

“To date there is no effective treatment for metastatic uveal melanoma, and there is an urgent need to identify novel precision therapies for advanced and metastatic uveal melanoma patients,” according to Justine S. Paradis, PhD, a postdoctoral fellow at the Moores Cancer Center at the University of California San Diego.


Trametinib is an inhibitor of MEK kinase activity, and VS-6766 is a second-generation RAF/MEK inhibitor blocking both the MEK kinase activity and the ability of RAF to phosphorylate MEK. 

The investigators explained that VS-6766 blocks MEK signaling without the compensatory activation of MEK, which differs from how other inhibitors work.

Defactinib (VS-6063) is an oral small-molecule inhibitor of FAK and PYK2 that is being evaluated as a potential combination therapy for various solid tumors.



Pearls for managing care of high-risk uveal melanoma patients

The combination of the 2 inhibitors induces apoptosis of the uveal melanoma cells, which in turn leads to rapid tumor regression in the uveal melanoma xenografts. When the 2 agents were used alone, the tumor growth was inhibited, but the size of the tumors did not shrink. 

In addition, this combination approach also decreased the tumor burden in models of uveal melanoma liver metastasis.

The investigators described that FAK and MEK inhibition combined showed “synergistic cytotoxic effects” in metastatic uveal melanoma cells.



The investigators used the combination of the MEK and FAK inhibitors in a xenograft mouse model in which the animals were treated for 20 days and found that the tumor volume decreased when the 2 were used together. 

In contrast, when used alone, the inhibitors only stabilized the tumor size, with a limited apoptotic response.



Conjunctival melanoma: Unlocking mysteries of disease

In a mouse model of liver metastasis, in which the animals were treated for 21 days, the investigators reported that the metastatic burden in the animals was reduced. The combination of the 2, they reported, very importantly “nearly eliminated all metastatic lesions.”

The team is evaluating residual disease and tumor burden progression after the treatments were stopped.

J. Silvio Gutkind, PhD, distinguished professor of pharmacology and associate director for Basic Science at Moores Cancer Center at the University of California San Diego, and senior investigator of the study, said results should lead to human trials.

“The study identified and reinforced FAK as a viable pathway to inhibit downstream from the GNAQ pathway, which is constitutively active in uveal melanoma,” he said. “We observed that cotargeting of FAK and RAF/MEK signaling led to tumor collapse in uveal melanoma xenograft and liver metastasis models in vivo.”



Liquid biopsies: Not yet ready for prime time in uveal melanoma 

Pharmacological inhibition of FAK and MEK inhibited the growth of uveal melanoma cells and had cytotoxic effects leading to tumor collapse in uveal melanoma xenograft and liver metastasis models in vivo.

The results emphasized the importance of cotargeting with FAK and RAF/MEK to provide a new network-based precision therapeutic strategy.

The signal-transduction-based precision therapy data support clinical testing of the combination inhibition in metastatic uveal melanoma.

VS-6766 and defactinib are also being studied clinically to treat low-grade serous ovarian and 

 mutant non–small cell lung cancers and colorectal cancer.

A phase 2 study of VS-6766 and defactinib in uveal melanoma is expected to commence in late 2020. 


Paradis has no financial interest in this subject matter.

Combining RAF/MEK signaling pathway inhibitor with FAK inhibitor raises bar