Patient-reported outcomes (PROs) are critical to an understanding of patient experience after laser vision correction (LVC). 

How the patient perceives the surgical outcome is just as important as the postoperative measurement of visual acuity (VA).

Julie Schallhorn, MD, an associate professor of ophthalmology at the University of California, San Francisco, pointed out the need for an appropriate way to measure patient perceptions given the frequent loss to follow-up of the patients who underwent LVC.

AI enhances customized myopic LASIK with ray tracing optimization


To shed light on this dilemma, Schallhorn and colleagues conducted a retrospective analysis of patients who underwent a primary bilateral LASIK or PRK procedure with targeted emmetropia between July 2014 and June 2016. 

The investigators analyzed the demographic, refractive, and PRO data obtained preoperatively and at months 1 and 3 postoperatively. 

The goal was to identify factors associated with loss to follow-up, patient satisfaction, and completion of the PRO measure, she recounted.

Data from about 37,000 patients who underwent a primary LVC were included. Of those, about 68% completed the PRO measure; the percentage at the 1-month visit was 54% and there was a 15% loss to follow-up, and the numbers at 3 months were 28% and 51%.

Transscleral laser therapy device simplifies procedure

Data analysis showed that patients who returned for follow-up and completed the PRO measure were more likely to be women. 

n addition, patients who underwent a PRK and had higher amounts of preoperative ametropia were more likely to return for follow-up and complete the PRO measure. 

When this information was combined in a multivariant logistic regression model, at month 1, older age (

 < .001), and higher amounts of myopic/hyperopic corrections (

 = .003) all were associated significantly with completion of the PRO measure.

“All of that is only important if it affects the patient satisfaction. If those variables have no effect on patient satisfaction, we would not expect them to alter our observations, regardless of loss to follow-up,” she said.

Treating vitreous opacities with YAG laser vitreolysis

The investigators then conducted an analysis of the patient-reported satisfaction in relation to the variables predictive of loss to follow-up and completion of the PRO measure.

“At 1 month, myopia/hyperopia, gender, age, procedure, and the postoperative binocular uncorrected VA/line below 20/16 all affected the patient satisfaction,” she said. By 3 months, all remained significant except for the procedure.


Regarding age, at both months 1 and 3, the older patients were more likely to both complete the PRO measure and to be dissatisfied with their VA.

The preoperative manifest spherical equivalent at 1 month showed no association between the spherical equivalent and completion of the PRO measure; however, at 3 months, patients with higher preoperative myopia and hyperopia were more likely to complete the PRO measure.

Robotics: Allowing surgeons to perform the seemingly impossible

“Most importantly, the postoperative VA was predictive of both PRO completion and patient satisfaction,” Schallhorn said. “Patients with worse VA were more likely to complete the PRO measure and were much less likely to be satisfied with their VA.”

Based on this analysis, she concluded that age, gender, preoperative refractive error, and postoperative VA all predict patient-reported satisfaction after LASIK and PRK, and all except the last predicted follow-up at 1 and 3 months postoperatively.

“Among the patients who completed the follow-up evaluations, the postoperative vision was strongly predictive of patient satisfaction and completion of the PRO measure,” she said.

Schallhorn noted that ophthalmologists cannot view PRO measures as a simple outcome of surgery and must take a more nuanced view.

Improving surgical safety, efficiency, and outcomes for patients

“Patients who undergo surgery have a visual outcome and factors from both the visual outcome and intrinsic factors present preoperatively result in either the patients being lost to follow-up or the decision to complete their PRO. The PRO data collection is heavily dependent on factors that influence the outcome,” she said, adding that she advises caution when analyzing and interpreting PRO data and understanding this, and hopes to delve deeper into what factors comprise patient satisfaction postoperatively and how to improve patient outcomes.


This article is adapted from Schallhorn’s presentation at the American Academy of Ophthalmology’s 2020 virtual annual meeting. Schallhorn is a consultant to Carl Zeiss Meditec and Vanda Pharmaceuticals and holds equity in Long Bridge Medical.

Articles

Investigators examine the demographic, refractive, PRO data measure.

Predicting laser vision correction results

This article is reviewed by William J. Johnson, MD



Corneal collagen crosslinking (CXL) appears to be a beneficial therapy that stops progression of keratoconus in children, according to William J. Johnson, MD, an ophthalmologist in Tifton, Georgia.

This is good news because keratoconus generally is more aggressive in pediatric patients. In addition, he noted, penetrating keratoplasties performed in children are associated with a guarded prognosis.

“CXL has provided a mechanism to arrest progression and avoid end-stage disease,” he said.

However, caveats for CXL include the ability to adequately test pediatric patients preoperatively, sedation requirements, and insurance coverage barriers.

COVID-19 impacts keratoconus patients waiting for corneal crosslinking


Erin D. Stahl, MD, section chief and pediatric ophthalmologist at University of Missouri-Kansas City School of Medicine and associate professor of ophthalmology at the University of Kansas School of Medicine, joined Johnson in conducting the study at Children’s Mercy Hospital in Kansas City, Missouri.

The medical records of the patients who had undergone CXL at Children’s Mercy Hospital were reviewed retrospectively. CXL was performed in all patients using the KXL system (Avedro) with Photrexa riboflavin preparations (Glaukos).

Following a superficial keratectomy and application of topical vitamin B2 every 2 minutes for 30 minutes, ultraviolet (UV)-A light (365 nm, 3 mW/cm2) was applied for 30 minutes with vitamin B2 continuing to be applied every 2 minutes during the UV light exposure. 


In patients whose corneas were too thin for endothelial protection despite application of hypotonic vitamin B2 to induce corneal edema, the UV light was blocked for part of the treatment, he explained.

The primary outcomes were the best-corrected visual acuity (BCVA), complications, treatment failure, and length of follow-up; if available, the tomographic and topographic data also were reviewed.


In 2015, a 13-year-old patient received a diagnosis of keratoconus based on retinoscopy reflex and topography and a marked increase in cylinder in the left eye (+2.25 x 075). 

Later that year, the cylinder again increased (-7.50+4.00 x 080) and the VA decreased to a BCVA of 20/30. In 2017, the patient underwent bilateral CXL; the central corneal thicknesses were 439 µm and 478 µm in the right and left eyes, respectively. 

More than meets the eye with corneal dystrophies



In 2019, at age 19, the cylinder had stabilized, the myopia in the left eye had decreased, and the BCVA was 20/25.



The study included 43 eyes of 27 patients (mean age at surgery, 15 years; median follow-up, 328 days).

“The logarithm of the minimum angle of resolution BCVA improved modestly from 0.3 preoperatively to 0.1 postoperatively,” Johnson said. Due to the small sample size, this was not statistically significant.

Postoperatively, many patients were fitted with a scleral contact lens, a particularly helpful adjunct when trying to provide optical rehabilitation and manage often irregular astigmatism in patients with keratometry beyond typical contact lens therapeutic ranges.



CXL imperative in treatment of pediatric keratoconus

The pachymetry and the topographic and tomographic data remained largely stable overall from preoperative to postoperative measurements.

When the investigators evaluated cases with a minimum of 6 months of follow-up, 26 eyes were included, the median preoperative and postoperative BCVA had a similar trend, the pachymetry was stable, and the topographic/tomographic data improved, although not significantly.


Johnson emphasized the need to follow the cohort over the long term despite the encouraging short-term safety and efficacy results. Although the treatment is designed to arrest progression of keratoconus, continued observation is needed, he said.

“The goal is to reach a point where a penetrating keratoplasty or even a partial-thickness deep anterior lamellar keratoplasty is not necessary at all,” he said. “The idea is to shepherd them through their younger years, during which time there is a higher risk of corneal transplantation [adverse] effects.”

Estimating the total corneal power key in keratoconus patients

A secondary outcome in these patients was a determination of whether CXL provided a safe and effective treatment that delayed progression to corneal transplantation and also strengthened the potential future graft-host junction to decrease the risk of recurrence in any future grafts, Johnson explained.

Johnson pointed out that although shorter protocols may be desirable to decrease anesthetic exposure or operating room utilization, efficiency should not override efficacy in these protocol assessments going forward.

Moreover, Johnson believes the safety of the treatment was demonstrated. One surgical complication resulted from an aggressive postoperative healing response that caused scarring. 

One episode of hydrops was likely progression of the keratoconus, given that it was more than a year after the surgery, which may occur in a small percentage of patients after CXL.

SARS-CoV-2 genomic RNA in corneal transplantation: Are corneal transplantations safe?

The short-term results suggested the effectiveness of CXL. One patient who lived a distance from the surgical center did not have access to a practitioner able to fit a scleral contact lens, so they underwent a penetrating keratoplasty to facilitate RGP fitting.

“There may be a need for more penetrating keratoplasties or partial-thickness transplants in this cohort in the future, but, to date, only 1 has occurred,” Johnson said.


Johnson pointed out that CXL in a pediatric population has been a safe procedure at the institution.

“Many findings in the FDA-approved CXL studies are similar to our current results, including stability, modest although nonsignificant BCVA improvement, and few complications,” he concluded. “Clinical judgment is a fixture in managing pediatric keratoconus and CXL because of the difficulty in obtaining definitive data in this patient population.” 


This article is adapted from Johnson’s presentation at the American Academy of Ophthalmology’s 2020 virtual annual meeting. Johnson has no financial interest in this subject matter.

Observation over the long term is needed to determine treatment efficacy. 

Corneal crosslinking outcomes look good for pediatric keratoconus 

A minimally invasive retinal reattachment procedure, which can be performed in an ophthalmologist’s office, may offer improved long-term integrity and structure of the retina's photoreceptors compared with more invasive operating room procedures, according to new research.

The study was led by investigators at St. Michael's Hospital of Unity Health Toronto, contributes to a growing body of evidence pointing towards pneumatic retinopexy (PnR) as the better first-line retinal reattachment technique to achieve the best visual outcomes.

According to investigators, retinal detachment is the most common surgical ocular emergency, progressing to loss of vision within hours or days. While there are a number of different treatment options, there is limited high-quality data guiding the choice of surgery.

"Our study shows there is a difference in the long-term integrity of the photoreceptors between different surgical techniques, and these anatomic differences were associated with visual outcomes," co-principal investigator Rajeev H. Muni, MD, a vitreoretinal surgeon at St. Michael’s and researcher at the Li Ka Shing Knowledge Institute, said in a statement.

During previous studies carried out at St. Michael’s Hospital, patients had better visual results following the less invasive PnR compared to pars plana vitrectomy (PPV). In the study, the investigators determined there was an actual difference in photoreceptor anatomic recovery between the two retinal reattachment techniques.

Using data from a randomly assigned trial conducted at St. Michael’s Hospital, investigators compared the retinal scans of 72 patients who had retinal reattachment using PPV and 73 patients who had retinal reattachment using the minimally invasive PnR at 12 months post-operatively.

According to investigators, PnR offers ophthalmologists a less invasive and less expensive retinal reattachment technique that can be done in the office. In PnR, a small gas bubble is used to close the retinal tear and allow the fluid to reabsorb naturally and slowly. PPV is a surgical technique where the fluid under the retina is rapidly aspirated and removed, forcefully bringing the retina back in position.

Investigators found that the imaging showed that discontinuity was more common at 12 months post-operatively among patients who had the PPV surgical reattachment than in patients who had the minimally invasive PnR procedure. The discontinuity indicates damage to cells that are critical for vision and this damage was found to be associated with worse visual outcomes.

“This data provides an objectively determined anatomic basis for the superior functional outcomes seen with pneumatic retinopexy that we have previously reported," according to Roxane J. Hillier, MD, the trial's other co-principal investigator who is now based in the United Kingdom.

The researchers say their findings highlight that closing the retinal tear, doing as little else as possible, and allowing the retina to reattach naturally leads to the best outcomes both from an anatomic and visual perspective.

"This was previously unknown, and in my opinion will be a game-changer in our field," Dr. Muni concluded.

1 Rajeev H. Muni, MD; Tina Felfeli, MD; Srinivas R. Sada, MD; et al; Postoperative Photoreceptor Integrity Following Pneumatic Retinopathy vs Pars Plana Vitrectomy for Retinal Detachment Repair; 

 Published online April 22, 2021. doi:10.1001/jamaophthalmol.2021.0803

A study led by investigators at St. Michael's Hospital of Unity Health Toronto supports pneumatic retinopexy as a primary retinal reattachment technique to achieve better long-term integrity of photoreceptors.  

Minimally invasive retinal reattachment procedure leads to enhanced photoreceptor integrity

He is director of The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, and chief medical editor of Ophthalmology Times.


Gene Bartow was an American collegiate basketball coach. In 1975, he began coaching the varsity team at a university in Southern California. 

In his first season, his team won its conference championship and reached the Final Four in the National Collegiate Athletic Association tournament to select the national champion. 

In his second season, they were again conference champs and again qualified for the national “March Madness” tournament. After 2 years, his team had won 52 games and lost 9.

Bartow’s average winning percentage of .852 placed him among the elite of the coaching pantheon, comparing favorably to the legendary Adolph Rupp (University of Kentucky) at .822, Dean Smith (Michael Jordan’s coach at the University of North Carolina at Chapel Hill) at .776, and Mike Krzyzewski (coach of perennial basketball powerhouse Duke University) at .764. 

Few coaches even reach the Final Four during their entire careers. For Bartow to accomplish this in his first year was quite a feat.

What was Bartow’s reward for this tremendous performance? Despite a remarkable 2-year record, Bartow was shown the door. He was guilty of an unpardonable sin—he was not John Wooden.

Wooden was the legendary basketball coach who preceded Bartow at the University of California, Los Angeles (UCLA), and who ended his career with a remarkable string of victories and national championships. As a result, fans came to expect national championships as their right.

Marques Johnson was a star player for UCLA under both Wooden and Bartow. Johnson said, “[Coach Bartow] was a sensitive person. He was used to being totally embraced as a coach and a person and he was just not ready for the kind of vitriol thrown at him when he took Coach Wooden’s place. He never came to grips with it, and it bothered him more than anything. After 2 years, he was gaunt and pale and he refused to read the Los Angeles newspapers because there was so much negativity. But he was a wonderful human being, a super nice guy, and a great coach.”

Whether Bartow was pushed out or left on his own to avoid a toxic situation may be debated. But no one disputes that he had incredible abuse heaped upon him.

Ironically, Bartow’s win-loss record at UCLA bested that of his revered predecessor. Wooden ended his (albeit much longer) career at UCLA with a winning percentage of .808. Few coaches who followed Bartow would match his winning percentage.

What possible relevance could this tale of 2 coaches hold for ophthalmologists and physicians in general? Just as with coaching jobs, from time to time a transition in leadership takes place in our medical practices, hospitals, departments, and divisions. 

When considering whether to throw one’s hat in the ring for a vacated leadership position, I think the wise ophthalmologist should take stock of the departing leader and any associated “cult” following. 

Like basketball coaches, no 2 medical executives are identical in their personalities, leadership styles, and priorities. As demonstrated in the case of Bartow, objectively demonstrable excellence might not be able to overcome the emotional attachment to a previous longstanding leader. 



1.Henderson M. Gene Bartow, man who followed John Wooden, dies. Patch. January 4, 2012. Accessed March 30, 2021. 

https://patch.com/california/ranchosantamargarita/gene-bartow-man-who-followed-john-wooden-dies

A word from Chief Medical Editor Peter J. McDonnell, MD.

Succession planning: Following an 'institution' can be tough

Ocuphire Pharma Inc. announced today that it has completed enrollment in the VEGA-1 Phase 2 clinical trial (

) evaluating the safety and efficacy of a combination kit of 0.75% phentolamine (Nyxol) and low-dose pilocarpine in presbyopia.

According to the company, VEGA-1 successfully recruited 150 subjects in just under 3 months.

According to Mina Sooch, MBA, president and CEO of Ocuphire Pharma, hitting the enrollment completion target for the VEGA-1 trial is another milestone in the company’s Nyxol program and tracks for top-line results by the end of June.

“Nyxol has the potential to address multiple unmet needs initially with the large market opportunity in reversal of mydriasis supported by our recent positive Phase 3 data results and then adding this very large presbyopia market opportunity that is estimated at over $5 billion in the US alone,” Sooch said in a statement. “We are excited to develop Nyxol with low-dose pilocarpine as a potential option for the growing number of presbyopic patients and to also realize commercial synergies if products are approved given the common targeted optometrists and ophthalmologists.”

Ocuphire noted that the global prevalence of presbyopia is estimated to be 2 billion. 

An estimated 120 million Americans live with presbyopia, a large prevalence that is expected to exceed 150 million by 2034. There are currently no approved drug therapies for presbyopia.

Moreover, when it comes to payment, presbyopia corrective devices generally have been mostly out-of-pocket cash pay by patients

Marguerite McDonald, MD, FACS, a clinical professor of ophthalmology at the NYU Langone Medical Center and an Ocuphire Medical Advisory Board member, pointed out that presbyopia is a condition that affects nearly everyone over the age of 40.

“Many patients reliant on reading glasses and contact lenses desire more flexibility and convenience and continually request alternatives or a complementary choice,” she said in a statement. “Development of eyedrop treatments for Presbyopia has recently become very active, led by Allergan having recently submitted an NDA for this indication.”

McDonald noted that there is room for many options given the large unmet need, and she said she is encouraged by Nyxol eye drops in combination with low-dose pilocarpine eye drops as a differentiated solution that works both on the iris dilator and sphincter muscles.

“This combination product should allow for moderate unopposed pupil constriction and provide the ability to see both at near and at distance without the side-effects such as brow ache, headache, blurry vision, and loss of distance night vision associated with the use of higher doses of pilocarpine,” she said.

According to a GlobalData market research report, 69% of patients would consider an eye drop as an alternative to reading glasses. 

More than 70% of patients indicated that they wear reading glasses in the morning, afternoon, and evening, suggesting that patients desire a solution with durability. 

More than 50% of responders also indicated that using drops 2 to 4 times per day would be moderately to very convenient to them. 

In addition, 66% of surveyed eyecare providers indicated interest in a Nyxol and low-dose pilocarpine product profile as a potential therapeutic alternative to reading glasses.


The VEGA-1 clinical trial is designed to evaluate the efficacy and safety of Nyxol in combination with low-dose pilocarpine compared to placebo in presbyopic subjects. A total of 150 subjects have been enrolled at 17 investigational sites in the US from mid-February to mid-May of this year.

The Phase 2 trial is randomly assigned, double-masked, placebo-controlled with 4 treatment arms. 

At the first visit, subjects are randomized to receive either Nyxol or placebo drops that are instilled at home near bedtime for 3 to 4 days prior to Visit 2; at Visit 2 subjects then receive either low-dose pilocarpine or no treatment with efficacy and safety measurements collected at multiple timepoints through 6 hours.

The primary endpoint is the percentage of subjects with ≥ 15 letters of improvement in photopic binocular near vision (i.e. distance-corrected near visually acuity, DCNVA) at 1 hour on Visit 2 for Nyxol + low-dose pilocarpine arm compared to placebo alone arm. 

Secondary endpoints at multiple timepoints include improvements of 3 lines of DCNVA without any loss of distance vision, pupil diameter, and improvements of DCNVA at 1 and 2 lines compared to placebo as well as to each Nyxol and low-dose pilocarpine alone.

Top-line results are expected by the end of Q2 2021.

Ocuphire collaborated closely with Oculos Development Services, a Tampa, Florida based clinical research organization and a subsidiary of Iuvo BioScience, on the launch and execution of the VEGA-1 trial.

“We are pleased by the rapid enrollment in this Phase 2 trial, which speaks to the unmet need of an eye drop to benefit vision correction for patients with presbyopia,” Chuck Slonim, MD, chief medical officer and medical monitor of Oculos Development Services, said in a statement. “We thank our investigators, clinical coordinators, staff, and subjects for their support and ease of trial execution at 17 sites across the US.”

Ocuphire Pharma has completed enrollment in the VEGA-1 Phase 2 clinical trial evaluating the safety and efficacy of drops to treat presbyopia. 

Enrollment completed in VEGA-1 Phase 2 clinical trial for presbyopia treatment

Imaging before treatment (left column) and repeated imaging again after two months of hydroxyurea treatment (right column). Before treatment, the patient exhibited between-session IPI of 3.0% and 2.7% respectively at the parafovea (A) and temporal retina (C). After two months of hydroxyurea, the between-session IPI was reduced to 0.5% and 1.6% respectively at the parafovea (B) and temporal retina (D). (Images courtesy of New York Eye and Ear Infirmary of Mount Sinai)

Ophthalmologists at New York Eye and Ear Infirmary of Mount Sinai have created a new technique to evaluate patients with sickle cell retinopathy and assess the disease before it progresses and leads to permanent vision loss.

Using optical coherence tomography (OCT) angiography--an advanced imaging system that captures the motion of red blood cells in blood vessels non-invasively--the researchers discovered that sequential imaging of affected retinal blood flow in sickle cell patients can help assess how the disease is progressing and how effective their treatment is for reducing focal vascular strokes.

According to lead investigator Toco Chui, PhD, director of the Marrus Adaptive Optics Laboratory at New York Eye and Ear Infirmary of Mount Sinai, investigators added a new dimension to ocular imaging technology that no one had thought of before.

“For the first time, we have shown that by doing rapid, repeated retinal imaging of sickle cell patients, you can see microscopic changes in blood vessels and blood flow,” Chui said in a statement. “The more the blood flow fluctuates across images, the more at risk patients are for a permanent blockage, which severely damage their eyesight."

Chui also pointed out that using the approach, investigators can non-invasively monitor the retina over time and see how a patient is doing before or after initiation of therapy.

Sickle cell disease is an inherited red blood cell disorder caused by a mutation in hemoglobin. The hemoglobin folds abnormally and distorts red blood cells into a sickle shape; the sickle-shaped cells clump together and can block blood flow. 

This causes repeated damage to capillaries, which become inflamed and sticky, resulting in permanent blockages that can affect vision in the retina, and in some cases, major bleeding and retinal detachment.

According to co-author Richard Rosen, MD, Belinda Bingham Pierce and Gerald G. Pierce, MD Distinguished Chair of Ophthalmology, and chief of Retina Services for the Mount Sinai Health System, investigators’ work can be a game-changer for sickle cell patients, especially for those who have no symptoms of retinopathy.

“It can lead to earlier diagnosis of retinal issues and prevention of irreversible blindness,” he said. “Without this technology, it is impossible to judge their eye condition until patients report vision loss, when it's too late."

Investigators analyzed 27 participants. Thirteen had sickle cell disease with retinopathy of varying severity levels. Some were on standard therapy (hydroxyurea) and others were not on treatment. The remaining 14 were controls, with no sickle cell disease or retinopathy.

According to investigators, the team used OCT angiography to image all subjects 10 times in a row over a 10-minute span. An hour later they repeated the imaging procedure. 

They analyzed the blood vessels that repeatedly opened and closed—a trait of sickle cell disease. When this happens, blood cannot flow freely and these blood vessels are at risk of permanent closure which can lead to blindness. 

For patients without sickle cell disease, scans showed that the blood vessels for the most part remained open, providing continuous blood flow.

Moreover, for each patient, the investigators stacked their groups of ten scans together and counted the blood vessels that "flickered." Healthy blood vessels remain white on all scans with no flickering, indicating consistent blood flow in the vessels.

On all scans, the untreated sickle cell patients had substantially more flickering (more intermittent blood flow) than patients on treatment, indicating that treatment was effective. 

Patients with no sickle cell disease had no or very minimal blood flow fluctuations. 

Investigators used measurements of flicker frequency and locations of flickering to develop a computer algorithm for assessing risk of retinal blood blockages in sickle cell patients.

Jeffery Glassberg, MD, director of Mount Sinai's Comprehensive Sickle Cell Program, for the first time ever in sickle cell disease, there are too many good drugs and too little information on who should be on what, and what combinations work best.

“What we hope is that OCT angiography and this new algorithm can be used to solve this problem. Instead of following lab tests and waiting for horrible things to happen to the patient, for the first time we can use this technology to measure the number of vaso-occlusive events that are occurring on a new treatment regimen to find out if it is best for the patient," Glassberg said in a statement.

Davis B. Zhou, a medical student from the Icahn School of Medicine at Mount Sinai, played a key role in creating the algorithm for the study during his extended research elective in the Einhorn Center for Clinical Research at the New York Eye and Ear Infirmary of Mount Sinai.

“Quantification of intermittent retinal capillary perfusion in sickle cell disease

” Davis B. Zhou, Maria V. Castanos, Alexander Pinhas, Peter Gillette, Justin V. Migacz, Richard B. Rosen, Jeffrey Glassberg, and Toco Y. P. Chui, 

Investigators develop technique to assess progression of sickle cell retinopathy

In an announcement this week, the Department of Health and Human Services’ (HHS) Office for Civil Rights (OCR) revealed it will enforce a prohibition on discrimination on the basis of sexual orientation and gender identity, citing a 2020 Supreme Court ruling.

According to the OCR, it will interpret and enforce Section 1557 and Title IX’s prohibitions on discrimination based on sex to include: (1) discrimination on the basis of sexual orientation; and (2) discrimination on the basis of gender identity. 

The agency said Section 1557 prohibits discrimination on the basis of race, color, national origin, sex, age, or disability in covered health programs or activities. 

The update was made in light of the U.S. Supreme Court’s decision in 

“The Supreme Court has made clear that people have a right not to be discriminated against on the basis of sex and receive equal treatment under the law, no matter their gender identity or sexual orientation. That’s why today HHS announced it will act on related reports of discrimination,” HHS Secretary Xavier Becerra said in a statement. “Fear of discrimination can lead individuals to forgo care, which can have serious negative health consequences.”

Becerra pointed out that the HHS position is that everyone, including LGBTQ people, should be able to access health care, free from discrimination or interference, period.

Discrimination in health care impacts health outcomes. Research shows that one quarter of LGBTQ people who faced discrimination postponed or avoided receiving needed medical care for fear of further discrimination.

According to Rachel Levine, MD, assistant secretary for health, the mission of the Department is to enhance the health and well-being of 

Americans, no matter their gender identity or sexual orientation.

“All people need access to healthcare services to fix a broken bone, protect their heart health, and screen for cancer risk,” she said in a statement. “No one should be discriminated against when seeking medical services because of who they are.”

According to the OCR, it is responsible for enforcing Section 1557 of the Affordable Care Act (Section 1557) and regulations issued under Section 1557, protecting the civil rights of individuals who access or seek to access covered health programs or activities. Covered entities are prohibited from discriminating against consumers on the basis of sexual orientation or gender identity.

According to Robinsue Frohboese, acting OCR director, its mission is to protect people from all forms of discrimination.

“OCR will follow Supreme Court precedent and federal law, and ensure that the law’s protections extend to those individuals who are discriminated against based on sexual orientation and gender identity,” Frohboese said in a statement.

On June 15, 2020, the U.S. Supreme Court held that Title VII of the Civil Rights Act of 1964 (Title VII)’s prohibition on employment discrimination based on sex encompasses discrimination based on sexual orientation and gender identity. 

 majority concluded that the plain meaning of “because of sex” in Title VII necessarily included discrimination because of sexual orientation and gender identity. 

Consistent with the Supreme Court’s decision in 

 and Title IX, beginning today OCR will interpret Section 1557’s prohibition on discrimination on the basis of sex to include: (1) discrimination on the basis of sexual orientation; and (2) discrimination on the basis of gender identity. 

This interpretation will guide OCR in processing complaints and conducting investigations, but does not itself determine the outcome in any particular case or set of facts.

In an announcement that could impact ophthalmologists, the Department of Health and Human Services’ Office for Civil Rights revealed this week that it will enforce a prohibition of discrimination on the basis of sexual orientation and gender identity.

HHS to enforce prohibition of sex discrimination on basis of sexual orientation, gender identity

Biogen Inc. on Friday announced topline results from the Phase 2/3 XIRIUS study of cotoretigene toliparvovec (BIIB112), a gene therapy being investigated as a one-time therapy for patients with X-linked retinitis pigmentosa (XLRP).

Patients living with XLRP currently have no approved treatments. The company noted that the XIRIUS study did not meet its primary endpoint of demonstrating a statistically significant improvement in the proportion of treated study eyes with ≥ 7 dB improvement from baseline at ≥ 5 of the 16 central loci of the 10-2 grid assessed by Macular Integrity Assessment (MAIA) microperimetry.

This assessment was performed at 12 months and compared to the study eye of patients randomized to the untreated control group. Positive trends were observed across several clinically relevant prespecified secondary endpoints.

Cotoretigene toliparvovec (BIIB112) is an investigational AAV8 vector-based gene therapy administered by subretinal injection, designed to provide full-length functioning retinitis pigmentosa GTPase regulator (

) protein in patients with X-linked retinitis pigmentosa (XLRP) caused by mutations in the 

By replacing the gene, cotoretigene toliparvovec leads to increased levels of the RPGR protein which may potentially slow, stop or prevent further degeneration of photoreceptors in patients with 

Katherine Dawson, MD, head of the therapeutics development unit at Biogen, noted that while the Phase 2/3 XIRIUS study of cotoretigene toliparvovec did not meet its primary endpoint, the company is encouraged by positive trends in other pre-specified clinically relevant endpoints, such as a measure of visual acuity under low light conditions.

“XLRP is a serious, early-onset form of retinitis pigmentosa, and people living with it face almost certain blindness by the end of the fourth decade, commonly leading to loss of independence, depression and unemployment,” she said. “We are working to further evaluate the data from the XIRIUS study before communicating potential next steps for the cotoretigene toliparvovec clinical development program.”

According to the company, most of the adverse events were ocular in nature, mild-to-moderate in severity, and resolved.

Complete analysis of the XIRIUS study is ongoing, and detailed results will be shared in a future scientific forum.

Biogen is advancing its multi-franchise portfolio strategy by pursuing modalities including gene therapy to address significant unmet medical needs. In ophthalmology, in addition to cotoretigene toliparvovec, the company is currently evaluating the safety and efficacy of timrepigene emparvovec (BIIB111/AAV2-REP1), a gene therapy being investigated for the one-time treatment of choroideremia, a rare inherited retinal disease.

The company also announced a global collaboration and licensing agreement with ViGeneron GmbH to develop and commercialize gene therapy products based on adeno-associated virus (AAV) vectors with the aim of treating inherited eye diseases as well as a licensing agreement with Massachusetts Eye and Ear to develop a gene therapy for the potential treatment of inherited retinal degeneration due to mutations in the 

 gene. In addition to Biogen’s gene therapy candidates for various ophthalmic conditions, the company also entered into an agreement with Catalyst Biosciences to develop and commercialize pegylated CB 2782 for the potential treatment of geographic atrophy, an advanced form of dry age-related macular degeneration that leads to blindness that has no approved therapies.

XIRIUS was a first-in-human, multicenter, randomly assigned, three-arm dose-escalation and dose-expansion study of a single subretinal injection of cotoretigene toliparvovec in males with a genetically confirmed diagnosis of X-linked retinitis pigmentosa. Part I was a 24-month dose-escalation study (n = 18, ≥ 18 years of age); Part II was a 12-month dose expansion study (n = 32 randomized ≥ 10 years of age), with a high dose and low dose selected from Part I based on a benefit/risk assessment and a third untreated group to allow for a controlled comparison of efficacy and safety. At study completion, treated subjects in Parts I and II have been invited to participate in a separate long-term follow-up study that will collect efficacy and safety data up to five years from treatment.

While Biogen’s XIRIUS study did not meet its primary endpoint of demonstrating a statistically significant improvement in treated eyes, positive trends were observed across several clinically relevant prespecified secondary endpoints.

Results unveiled from phase 2/3 gene therapy study for XLRP

The results of a case series reported by ophthalmologists in Hubei Province, China, found that about one-third of patients with 

While a large number of people have been infected with 

 worldwide, few studies have reported ocular abnormalities associated with the virus.

“Understanding the ocular manifestations of patients with 

 by ophthalmologists and others may facilitate the diagnosis and prevention of transmission of the disease,” the investigators stated.

In this retrospective case series, led by lead author Ping Wu, MD, patients with COVID-19 in a Hubei Province hospital between February 9 to 15, 2020, were reviewed for ocular findings. 

The investigators looked at the ocular signs and symptoms and results of blood tests and reverse transcriptase–polymerase chain reaction (RT-PCR) from nasopharyngeal and conjunctival swabs for  

Wu is from the Department of Ophthalmology at the The First College of Clinical Medical Science, Yichang Central People’s Hospital, China Three Gorges University, Yichang, China.

A total of 38 patients (25 men; mean age, 65.8 years) with confirmed cases of COVID-19 were included in the study; 28 of the 38 showed positivity for the virus by RT-PCR analysis of the nasopharyngeal swabs. 

Twelve of the 38 patients (31.6%) had ocular manifestations that were consistent with conjunctivitis, including conjunctival hyperemia, chemosis, epiphora, or increased secretions.

Of the 12 patients with ocular findings, RT-PCR showed positivity for COVID-19 from nasopharyngeal swabs in 11 (91.7%), and COVID-19 positivity by RT-PCR was seen in 2 patients from both conjunctival and nasopharyngeal swabs, the investigators reported.

The investigators reported that “patients with ocular symptoms were more likely to have higher white blood cell and neutrophil counts and higher levels of procalcitonin, C-reactive protein, and lactate dehydrogenase than patients without ocular symptoms.”

Based on the findings, the authors concluded that about one-third of patients had ocular manifestations, which frequently occur in patients with more severe COVID-19 and that even though there is a low viral prevalence in tears, it is possible to transmit the virus via the eyes. 


1. Wu P, Duan F, Luo C, et al. Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol 2020;138:575-8. doi:10.1001/jamaophthalmol.2020.1291

According to investigators, understanding the ocular manifestations in patients with COVID-19 could ultimately help with the diagnosis and prevent transmission. 

Shedding light on ocular findings in COVID-19 patients

The preliminary results of 2 ongoing phase 1/2 clinical trials evaluating the effects of subretinal gene therapies for achromatopsia (ACHM) indicate that both drugs, AGTC-401 and AGTC-402 (Applied Genetic Technologies Corp. [AGTC]), seem safe and well tolerated in patients with ACHM.

It is noteworthy that data from both studies are showing encouraging signs of biologic activity, according to Mark E. Pennesi, MD, PhD, associate professor of ophthalmology and Molecular and Medical Genetics Kenneth C. Swan Endowed Professor, division chief, Ophthalmic Genetics, Oregon Health and Science University Casey Eye Institute, Portland, OR.

ACHM is an autosomal recessive disease that causes a cone dysfunction syndrome, with the bulk of the mutations in 2 genes, 

Two clinical trials of the affected genes are underway, one is a long-term follow-up gene therapy study for achromatopsia CNGB3 and CNGA3, at the Moorfields Eye Hospital, London, and Kellogg Eye Center, Ann Arbor, MI, and the other is a natural history study of achromatopsia CNGB3 and CNGA3, at Moorfields Eye Hospital.

Patients with ACHM have poor central vision in the range of 20/100 to 20/200, nystagmus, color vision defects, photophobia, and high myopia. The disorder is nonprogressive in contrast to cone-rod dystrophy. 

Electroretinography (ERG) shows severely decreased cone function but normal rod function, Pennesi explained.


Both trials are phase 1/2, open-label, dose-escalation studies using recombinant adeno-associated virus (rAAV) viral vectors.

The enrolled patients were treated with 1 subretinal injection of either AGTC-401 (rAAV2tYF-PR1.7-hCNGB3; 26 patients) or AGTC-402 (rAAV2tYF-PR1.7-hCNGA3; 19 patients) into the macular region on 1 eye (study eye). All patients were 14 years or older.

Participants were sequentially assigned to 1 of 4 dosing groups in both studies. The primary study endpoints were changes in the best-corrected visual acuity, light discomfort testing by ocular photosensitivity analyzer, ERG and multifocal ERG, retinal sensitivity by static perimetry and microperimetry, color vision testing using the Farnsworth D15 and color assessment and diagnosis tests, and patient-reported outcomes using the quality-of-life Visual Light Sensitivity 

Mark Pennesi, MD, PhD, reports during ARVO 2021 that preliminary results have shown that AGTC-401 and AGTC-402 seem safe and well tolerated in patients with ACHM.

Results unveiled from phase 2/3 gene therapy study for XLRP

Shedding light on ocular findings in COVID-19 patients

The first steps in gene therapy for achromatopsia