Cheryl Guttman is a medical writer based in Deerfield, Ill.



BIGH3 (transforming growth factor-β-Induced Gene Human Clone 30) is a promising serum biomarker for 

 in patients with nonproliferative diabetic retinopathy (NPDR), said Andric Perez-Ortiz, MD, MPH, who presented research at ARVO 2020.

Perez-Ortiz and colleagues conducted a case-control study analyzing levels of BIGH3, transforming growth factor-β1 (TGF-β1), and TGF-β2 in the aqueous humor and serum of patients with 

and unaffected controls. 

The results showed that BIGH3 was the only cytokine that was present in a significantly different concentration in both fluids in

 patients compared with controls and the only cytokine with a positive significant correlation between its level in aqueous humor and serum. 



Turning to new frontier in micropulse laser treatment for retinal disorders

None of the three cytokines, however, correlated with macular thickness or OCT phenotype among patients with

“Studies investigating expression and levels of these cytokines have all been performed in vitro. The aim of our study was to measure the concentrations of TGF-β1, TGF-β2, and BIGH3 in aqueous humor of patients with NPDR with and without DME and to assess their clinical applicability as serum markers by testing their correlation in aqueous humor and serum and association with macular thickness and DME phenotype,” said Perez-Ortiz, associate professor, Department of Public Health Universidad Panamericana Sede México, Mexico City, and research fellow, Department of Surgery, Massachusetts General Hospital, Boston, MA. “The predictive capacity of BIGH3 warrants further study, especially its sensitivity and specificity and/or predictive use as an early biomarker for DME development.”

Interest in exploring the potential for TGF-β1, TGF-β2, and BIGH3 to serve as biomarkers for DME is based on understanding of their role in the pathogenesis of DR and 

. 

Perez-Ortiz explained that pericyte dropout and increased inflammation and activation of proinflammatory transcription factors that induce monocyte and macrophage infiltration occur early in the pathogenesis of these diabetic eye diseases. 

Macrophages predominantly secrete TGF-β1 and TGF-β2 that induce apoptosis of retinal pigment epithelial (RPE) and upregulation of the gene encoding for BIGH3.



Identifying biomarkers to predict diabetic retinopathy progression

BIGH3 is an extracellular matrix protein that can act in an autocrine or paracrine manner to induce apoptosis of RPE cells, pericytes, and retinal endothelial cells in a time and dose-dependent fashion. 

The presence of BIGH3 has been observed in the histopathologic retinal section of a post-mortem globe with documented NPDR deposited predominantly around retinal vessels and occasionally in choroidal vessels.

“Hence, it has been hypothesized that monocyte/macrophage-induced BIGH3 expression is an important progressive step in the pathophysiology of pericyte loss,” Perez-Ortiz said.



The study investigated the levels of the TGF-β cytokines and BIGH3 in patients with NPDR included adults 18 years and older with type 2 diabetes mellitus who were undergoing a surgical procedure (initiation of intravitreal injection for DME patients and cataract surgery for controls). It included 26 patients with DME and 27 patients without 

. 

Patients were excluded if they had systemic inflammatory disease or a history of any vitreous procedure. 

The aqueous humor sample of approximately 1 µL was collected in all eyes prior to any surgical intervention, and the cytokine levels in serum and aqueous humor were quantified with cytometric-bead assays.



Research suggests course of diabetic eye disease influenced by genetic factors

The two groups were similar in mean age (~63 years) and sex distribution, but the average time since diabetes diagnosis was significantly longer in the DME patients than in the controls. 

As would be expected, maximum central macular thickness (CMT) was also significantly greater in the cases compared with controls. 

Among patients with 

, cystic changes and spongiform changes were the most common phenotypes identified on OCT.

The cytokine analyses showed that the aqueous humor concentration of TGF-β1 was significantly greater in the DME eyes compared with the controls, whereas the reverse relationship was observed in serum. 

TGF-β2 was also present in a significantly higher concentration in the aqueous humor of the cases compared with controls, but its concentration in serum did not differ significantly between the two groups.



Researchers advocate for intraoperative intravitreal steroid during cataract surgery in DME eyes

Further analyses showed that the ratio of TGF-β1 in aqueous humor:serum was disproportionately elevated in the DME cases compared with controls. 

In addition, a significant positive correlation was found in the 

 group between aqueous humor concentration and maximal CMT. 

The correlation between serum concentration and maximal central macular thickness was negative for TGF-β1 and positive for TGF-β2.

The concentration of BIGH3 was significantly higher in both serum and aqueous humor in the DME group compared with controls. 

The ratio of BIGH3 concentration in aqueous humor:serum was not significantly different comparing cases and controls, and it did not correlate with CMT or OCT subtypes in the eyes with DME.


None of the investigators has any relevant financial interests to disclose.

Articles

BIGH3 is an extracellular matrix protein that can act in an autocrine, paracrine manner.

Investigators explore pathogenic cytokines as biomarkers for DME


From patient care and treating glaucoma to the ongoing pandemic, ophthalmologists share the most pressing thoughts of concern leaving them awake at night.

Watch the first two installments:

What keeps you up at night in ophthalmology: Part II

Videos

From patient care and treating glaucoma to the ongoing pandemic, ophthalmologists share the most pressing thoughts of concern leaving them awake at night.

What keeps ophthalmologists up at night: Part III

Ong is a medical student at the University of Pittsburgh School of Medicine. 

Brunstetter is a U.S. Navy Aerospace Optometrist and SANS specialist at the NASA Johnson Space Center in Houston, Texas. 


Tarver is a flight surgeon and SANS specialist at the NASA Johnson Space Center in Houston, Texas. 


Mortensen is a Neuro-Ophthalmology Fellow at the Houston Methodist Hospital. 


He is editor of The Neuro-Connection. He is professor of ophthalmology, neurology, and neurosurgery, The H. Stanley Thompson Neuro-ophthalmology Clinic, Department of Ophthalmology at the University of Iowa Hospitals and Clinics, Iowa City.


Ophthalmology continues to play a major role in the characterization and mitigation of one of the highest-priority risks for astronauts during extended spaceflights––spaceflight-associated neuro-ocular syndrome (SANS).

SANS represents the collective neuro-ophthalmic changes found in astronauts who have been exposed to extended periods of microgravity during long-duration spaceflights (LDSFs).


Previously known as visual impairment intracranial pressure (VIIP) syndrome, SANS has a high “likelihood and consequence” rating from the National Aeronautics and Space Administration (NASA), which requires a mitigation plan for missions that range from 1 to 3 years (planetary and deep space habitation.

Telemedicine continues to make waves in ophthalmology 



VIIP became known as SANS because of the emerging hypothesis that the condition’s etiology may not stem primarily from intracranial hypertension alone and may, although being possibly multifactorial, require further investigation.

During LDSF, astronauts are subjected to extended exposure in the microgravity environment, which serves as the primary risk factor for SANS. Approximately 60% of astronauts who underwent LDSF reported a decrease in distance and near visual acuity.

Further, findings from case studies have shown that some astronauts flying on missions longer than 30 days had baseline ocular anatomic changes, which clinicians observed in fundoscopy, orbital ultrasonography, 

These neuro-ocular anatomical changes included optic disc edema, hyperopic shift, cotton wool spots, globe flattening, and choroidal folds (Figure 1).

 

The total percentage of study participants with findings of SANS, including optic disc edema, cotton wool spots, choroidal folds, globe flattening, and refractive error, ranges from 37.5% to 51%.

Neuro-ophthalmology, NFL connect for a touchdown 



Some of these anatomical changes continue to be seen during subsequent postflight follow-ups, and several astronauts have noted that their microgravity-induced refractive errors persist years after their LDSF mission. 

Our understanding of the specific pathophysiology behind SANS has evolved over time and 2 current theories behind this unique manifestation of neuro-ocular symptoms have emerged.

The first theory stems from the changes in intracranial pressure that arise from cephalad fluid shifts in astronauts.

 Results of studies in transient microgravity have shown a physiological jugular venous distension (JVD), which alludes to possible cerebral and internal jugular venous congestion leading to the intracranial hypertension and subsequent optic disc edema seen in SANS.

However, the persistence of optic disc edema after astronauts return to Earth, asymmetric disc swelling, and absence of additional clinical findings in intracranial hypertension, such as severe headaches and tinnitus, suggest that increased intracranial pressure may not be the sole underlying cause of SANS.



Cutting-edge neuro-ophthalmology: Combining artificial intelligence, eye tracking 

In addition, although intracranial pressure readings in astronauts post-LDSF have been elevated, they fall nearly within normal limits and do not reach the expected elevation of pressure that is seen in typical patients with intracranial hypertension.

These findings ultimately suggested that intracranial pressure may not be the sole explanation for SANS and sparked further discussion for the second theory of the condition’s pathophysiology.

The second leading theory hypothesizes that the cerebrospinal fluid (CSF) becomes compartmentalized or “accumulates” inside the optic nerve sheath due to a one-way valve-like system during microgravity.

This CSF compartmentalization results in a heterogenous pressure gradient between the CSF pressure in the optic nerve sheath and the CSF surrounding the brain. 

The difference in pressure between these 2 areas could explain the nearly normal intracranial pressure and absence of intracranial hypertension symptoms but extensive disc edema that clinicians see in astronauts.

The pathogenesis behind SANS continues to be a subject of investigation, and investigators are conducting further studies with astronauts to understand more about SANS’ etiology.



Glaucoma mystery: Focus on deep optic nerve structures 

Currently, astronauts are using different powers of reading glasses (formerly “space anticipation glasses”) that have an increased diopter strength to help mitigate the visual acuity changes when their normal prescription glasses are no longer strong enough to carry out tasks on board the International Space Station (ISS).

The overall prognosis in astronauts with SANS findings has been variable, but no permanent vision loss has been reported due to LDSF on the ISS. 

However, there are reports of persisting choroidal folds years after a mission, as well as hyperopic visual changes that have yet to resolve.

With NASA’s sights set on Mars, continued research into further understanding and mitigating SANS is of the utmost importance for astronaut health and space exploration. 



Ong is a medical student at the University of Pittsburgh School of Medicine. Joshua has no financial interests relevant to the subject matter. 


 
Mortensen is a Neuro-Ophthalmology Fellow at the Houston Methodist Hospital. Mortensen has no financial interests relevant to the subject matter. 



Brunstetter is a U.S. Navy Aerospace Optometrist and SANS specialist at the NASA Johnson Space Center in Houston, Texas. Brunstetter has no competing financial interests relevant to the subject matter. 




Tarver is a flight surgeon and SANS specialist at the NASA Johnson Space Center in Houston, Texas. Tarver has no competing financial interests relevant to the subject matter. 




Lee, editor of The Neuro-Connection column, is affiliated with the Blanton Eye Institute, Houston Methodist Hospital. He did not indicate proprietary interest.

1. Stenger M.B., Tarver W.J., Brunstetter T.et al. Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS). NASA Human Research Program Human Health Countermeasures Element 

https://humanresearchroadmap.nasa.gov/evidence/reports/SANS.pdf

https://humanresearchroadmap.nasa.gov/evidence/reports/SANS.pdf?rnd=0.434276635495143

https://humanresearchroadmap.nasa.gov/Risks/risk.aspx?i=105

2. Mader TH, Gibson CR, Pass AF, Kramer LA, Lee AG, Fogarty J, Tarver WJ, Dervay JP, Hamilton DR, Sargsyan A, Phillips JL, Tran D, Lipsky W, Choi J, Stern C, Kuyumjian R, Polk JD. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology. 2011 Oct;118(10):2058-69. doi: 10.1016/j.ophtha.2011.06.021

3. Mader TH, Gibson CR, Pass AF, Lee AG, Killer HE, Hansen HC, Dervay JP, Barratt MR, Tarver WJ, Sargsyan AE, Kramer LA, Riascos R, Bedi DG, Pettit DR. Optic disc edema in an astronaut after repeat long-duration space flight. J Neuroophthalmol. 2013 Sep;33(3):249-55. doi: 10.1097/WNO.0b013e31829b41a6

4. Lee, A.G., Mader, T.H., Gibson, C.R. et al. Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update. npj Microgravity 6, 7 (2020). 

https://doi.org/10.1038/s41526-020-0097-9

5. Mader TH, Gibson CR, Otto CA, Sargsyan AE, Miller NR, Subramanian PS, Hart SF, Lipsky W, Patel NB, Lee AG. Persistent Asymmetric Optic Disc Swelling After Long-Duration Space Flight: Implications for Pathogenesis. J Neuroophthalmol. 2017 Jun;37(2):133-139. doi: 10.1097/WNO.0000000000000467

Spaceflight-associated neuro-ocular syndrome a potential challenge during long missions. 

Investigators research ocular health after space flight 


This article was reviewed by Yusen Huang, MD



Adding cefuroxime to the irrigating solution used during cataract surgery appears to be a safe and effective method for reducing the risk of postoperative endophthalmitis, according to researchers who reported their experience with this technique in a recently published retrospective study.

The investigation included 61,299 eyes. Of the total cohort, 15,948 eyes were operated on between January 1, 2012, and December 31, 2014, using plain balanced salt solution (BSS) as the irrigating solution (control group), and 45,351 eyes underwent cataract surgery between January 1, 2015, and December 31, 2019, using irrigating solution that contained cefuroxime 1500 µg/mL. 



 Eliminating risk of endophthalmitis during intravitreal injections for patients wearing masks



The mixture was prepared by withdrawing 10 mL BSS from the irrigating solution and injecting it into a vial of cefuroxime 750 mg. The reconstituted solution was injected back into the BSS container.

The rate of endophthalmitis was significantly decreased after the transition to intraoperative irrigation with cefuroxime. Endophthalmitis occurred in 11 eyes (0.07%) in the group that did not receive intraoperative cefuroxime and in 5 eyes (0.01%) when cefuroxime was used in the irrigating solution (

 < .01). 

Cultures were positive for bacteria in 4 of the 11 cases in the control group and in 1 of the 5 eyes in the intraoperative cefuroxime group (

 > .05). No safety issues were associated with intraoperative cefuroxime irrigation.

Discussing the research, Yusen Huang, MD, PhD, of the Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences in Qingdao, People’s Republic of China, pointed out that although intracameral antibiotics are already widely accepted as a method for endophthalmitis prophylaxis in patients undergoing cataract surgery, the optimal choice of prophylactic routes and antibiotics is controversial.

“In European countries, commercial cefuroxime formulation (Aprokam) has been widely used, and the dose administered is the same as in the European Society of Cataract and Refractive Surgeons’ (ESCRS’) randomized prospective study demonstrating its efficacy,” Huang said. 

Surgeons have been reluctant to adopt intracameral cefuroxime because it is off label and carries potential risks.



Research: Similar endophthalmitis rates for generic, branded topical antibiotics 


“In our study, the manner of cefuroxime preparation was modified so that it involved only a 1-step process. This makes it simpler, saves resources, and could reduce the potential risks of both preparation errors and contamination,” Huang pointed out. “Although the intracameral concentration achieved with our approach is estimated to be 1500 µg/mL, or only about 45% of the ESCRS recommendation, we found that it reduced the rate of postcataract surgery endophthalmitis by about sevenfold.”

Furthermore, Huang explained that “during the last 2 years in our hospital where more than 25,000 cases of cataract surgery have been performed using intraoperative cefuroxime irrigation, not a single patient developed endophthalmitis. 

It should be noted, however, that this method is not recommended for use in patients with a history of vitrectomy, [considering] the potential for rapid posterior segment diffusion of the antibiotic and potential macular toxicity.”

AAO live: Drop-free prophylaxis regimen before cataract surgery lowers treatment burden with caveats

Although adding cefuroxime to the irrigating solution is still an off-label use of the medication, the authors suggested that it represents a good option for countries with no licensed product for intracameral use of endophthalmitis prophylaxis and particularly in developing regions where the risks for both endophthalmitis and a poor outcome may be higher given a variety of contributory factors.

Throughout the entire study period, all patients received the same preoperative antisepsis with application of topical povidone-iodine. 

In addition, all patients started using topical levofloxacin 0.5% solution preoperatively and continued it postoperatively, along with a topical steroid and topical nonsteroidal anti-inflammatory drug.



Minimize inflammation after cataract surgery


Postoperative follow-up visits were scheduled at 1 and 4 days, 4 weeks, and 12 weeks, but patients were instructed to seek care if they developed pain, redness, or loss of vision. 

The analyzed outcome was onset of acute-onset endophthalmitis, which was diagnosed if a patient presented within 6 weeks of surgery with eye pain, anterior chamber reaction or flare, hypopyon, and/or vitritis with causes for intraocular inflammation other than endophthalmitis excluded.

The 16 cases of endophthalmitis recorded during the 9-year study period developed at a median of 7.56 days after cataract surgery (range, 1-21 days). 

None of the cases occurred in a patient who had an intraoperative complication or was noted to have incision leakage at the time endophthalmitis was identified.



Perioperative medications can eliminate postoperative drops after cataract surgery

Isolates from the culture-positive cases of endophthalmitis in the control group included 

 was identified as the causative pathogen in the culture-positive case of endophthalmitis among patients who received intraoperative cefuroxime, and the organism was found susceptible to cefuroxime.



1. Ma X, Zie L, Huang Y. Intraoperative irrigation prophylasix for acute-onset endophthalmitis after phacoemulsication surgery. 

Findings from retrospective study support intraoperative cefuroxime irrigation.  


Investigators focus on preventing postcataract surgery endophthalmitis

Delivery into the suprachoroidal space may potentially extend the duration of therapeutic action and reduce or relieve the treatment burden for wet AMD.

Clearside Biomedical's axitinib injectable suspension phase 1/2a trial enrolls first patients

 announced today the successful completion of a pre-investigational new drug (IND) meeting with the U.S. Food and Drug Administration (FDA) for its candidate AMDX-2011P, a small-molecule retinal tracer that targets amyloid beta to diagnosis amyloid angiopathy.

According to a company news release, Amydis has reached an agreement with the FDA for both nonclinical and clinical plans.

Additionally, the company reported that the FDA supports its adaptive Phase 1/2a first-in-human (FIH) clinical development plans for evaluating AMDX-2011P as a potential retinal tracer to diagnose patients with cerebral amyloid angiopathy (CAA).

“This feedback from the FDA is a significant milestone for Amydis,” said Stella Sarraf, PhD, founder and CEO of Amydis, in the release. “We are pleased to have reached agreement with the FDA on our clinical plan for AMDX-2011P in CAA patients and we appreciate the FDA’s guidance on our path to introduce this new class of ocular tracers.”

A major cause of spontaneous intracerebral hemorrhage in patients age 55 and up, CAA is a major contributor to age-related cognitive decline.

Current technology for CAA diagnoses includes imaging testing and requires physicians to acquire a brain tissue sample. In comparison, Amydis’s retinal tracer is designed to provide accessible and affordable retinal testing for patients.

Amydis announced the successful completion of a pre-investigational new drug (IND) meeting with the FDA for its candidate AMDX-2011P, a small-molecule retinal tracer that targets amyloid beta to diagnosis amyloid angiopathy.

Amydis reports successful pre-IND meeting with FDA to develop retinal tracer for amyloid angiopathy diagnosis


In a letter to the secretary of the U.S. Department of Health and Human Sevices, the American Hospital Association (AHA) is urging the federal government to expedite the administration of COVID-19 vaccines.

In the letter, sent to Alex Azar, secretary of the Department of Health and Human Services and signed by AHA President and CEO Richard J. Pollack, the organization said that amid the rollout of the first vaccinations last month, the rollout has since been slow, heightening concerns about whether vaccinating the nation would move as quickly as federal leaders had claimed it would.

“Effective vaccines, if administered properly to enough Americans, can tame this awful virus and halt the devastating impact it has had on the country,” the letter read. “But, hope alone will not be the remedy.”

Pollack said the organization shares the goal of rapidly vaccinating as many individuals as needed to get to a level of herd immunity that will allow the country to return to normal activities, according to the letter.

“In the first few weeks of administering vaccines, hospitals have seen a number of barriers to smooth and effective vaccinations

We raise these to your attention so that you and your team can begin to eliminate the barriers and expedite vaccination.”

In the letter, the AHA noted that the barriers include:

The goal of vaccinating 75 percent of 328 million Americans by the end of May would require 1.8 million people getting the jab everyday between Jan. 15 and May 31, including weekends and holidays. There are currently 64 different microplans devised by states, large cities, and other jurisdictions, but has HHS assessed whether these plans are capable achieving this goal or is HHS working to amend the plans so that they do?

 While HHS has offered initial guidance and support, the vaccination effort requires ongoing and visual coordination with critical stakeholders including prompt decision-making. Tasks must be simplified and standardized to avoid unnecessary confusion and complexity which can impede making progress in vaccinating the public.

 Everyone will want to know the how the rollout is going, whether there are any delays, and what is being done to resolve any issues. Showing the progress of the vaccination effort to reach the 75 percent goal would grant greater insight.

In the letter, the organization also urged Azar to establish a process within HHS with the ability to be able to coordinate the national efforts among all of the states and jurisdictions and the many stakeholders; answer all of the questions expeditiously; establish and maintain effective communication among all involved; and identify and resolve barriers to the rapid deployment of millions of doses of vaccines.

In a letter to Health and Human Services Secretary Alex Azar, the American Hospital Association is urging the federal government to expedite the administration of COVID-19 vaccines.


AHA seeking expedited administration of COVID-19 vaccines


This article was reviewed by Nancy J. Newman, MD

The developer of a gene therapy for patients with Leber hereditary optic neuropathy (LHON) caused by a mutation in the 

 gene applied for European marketing authorization of the therapy in September 2020. 

According to the company, GenSight, LUMEVOQ (GS010; lenadogene nolparvovec) targets LHON by specifically targeting the 

 mitochondrial gene mutation, which is the most common cause of the disease.

Investigators evaluated LUMEVOQ in the RESCUE and REVERSE trials. The 2 studies found that in 76% of the patients in the RESCUE study and 71% of those in the REVERSE study, there was a “rate of clinically meaningful improvement from a nadir of at least 0.3 [logarithm of the minimum angle of resolution],” which translates to at least 3 lines of Snellen visual acuity, GenSight reported.



Gene therapy zeroes in on LHON treatment 

These findings are especially important considering the nature of LHON, a genetic disease that affects patients bilaterally. Spontaneous recovery of LHON is rare in those with a mutation in the ND4 gene. 

For patients who experience visual loss when they are age 15 years or older, the percentage who have some visual recovery is only 11.3%, according to a recent meta-analysis published in the 

The challenge for physicians has been to estimate the rate of visual recovery given the small numbers of affected patients, which usually ranges from about 800 to 1200 new cases annually in the United States and Europe.

The investigators, led by Nancy J. Newman, MD, pointed out that visual prognosis associated with LHON is generally poor, with most patients’ visual acuity worsening to at least 20/200. 

In addition, there are few treatments for LHON, and clinical trials are hampered because there is little information about the natural history of vision loss and recovery. In light of this information gap, researchers conducted a meta-analysis with the hope of expanding the body of information about LHON with this mutation.

Newman is from the departments of ophthalmology, neurology, and neurological surgery at the Emory School of Medicine in Atlanta, Georgia.



Research shows promising results for LHON gene therapy 


Investigators were able to identify 12 retrospective studies and 3 prospective studies that, in total, provided visual function information on 695 patients with LHON caused by the m.11778G>A mutation. 

Of these patients, the investigators found that “100 (14.4%) … were reported to have ‘recovered’ some vision, although definitions of ‘recovery’ varied among studies.”

When they considered the age at which the vision loss began and those who were at least 15 years of age, the investigators noted “meaningful visual recovery occurred in 23 of 204 (11.3%) patients. 

A younger age at onset, especially less than 12 years, portends a better visual prognosis and a different natural history of visual loss progression and recovery than in adults.”

Gene panel offers expanded diagnostic capability of inherited retinal diseases


The key findings of the meta-analysis, which provided an actual picture of the course of visual function in these patients, were as follows. 

The classic presentation of LHON in which patients with the m.11778G>A mutation have a severe loss of vision with rare or poor recovery from the nadir is true for most of the patients.

According to the team of investigators, among the patients aged 15 years and older, the percentage of patients who experience meaningful visual recovery “likely occurs in less than 20% of patients, irrespective of how recovery is defined, and ultimate visual acuities of better than 20/200 are rare.”



The investigators noted the importance of future prospective studies with enough genotypically homogeneous untreated patients with LHON.



Ocular gene therapy offers hope for inherited retinal disease

The studies that would yield the best information are those that the patients are stratified by age, enrolled immediately upon becoming symptomatic, and then followed regularly for a sufficiently long time during which they undergo consistent measures of visual function with standard definitions of visual improvement to clarify the natural order of the disease.

GenSight pointed out that the findings of the meta-analysis lend weight to the findings of the trials in which LUMEVOQ was evaluated. 



Newman is a consultant for GenSight, Santhera Pharmaceuticals, and Stealth BioTherapeutics, and reported receiving research support from GenSight and Santhera Pharmaceuticals.


1. Newman NJ, Carelli V, Taiel M, Yu-Wai-Man P. Visual outcomes in Leber hereditary optic neuropathy patients with the m.11778G>A (MTND4) mitochondrial DNA mutation. 

A new gene therapy for this patient population targets the ND4 gene mutation.

Leber hereditary optic neuropathy: Outlining disease’s natural course

 cases continue to spike in many parts of the United States, health officials continue to deal with myriad shortages, including much-needed medications.

Treatment delays, even temporary, can be detrimental to a patient’s health. The U.S. Food and Drug Administration (FDA) can take action to help prevent drug shortages and protect treatment access without compromising the 

Over the last several months, Prevent Blindness, has stepped up to ensure that patients do not face shortages of medications that help protect their vision. The organization is concerned about shortages of teprotumumab (Tepezza, Horizon Therapeutics).

Jeff Todd, president and CEO of Prevent Blindness, pointed out that the Food and Drug Administration in 2020 approved teprotumumab for the treatment of thyroid eye disease (TED). 

He has lead the organization’s efforts to guard against potential lapses in therapy for patients living with TED. Teprotumumab currently is the only FDA-approved treatment of the underlying causes of TED.

Sara Brown, director of government affairs at Prevent Blindness, noted that the organization is concerned that the manufacturing of teprotumumab has been limited due to the manufacture of the COVID-19 vaccine.

“We believe the production of the COVID-19 vaccine is of the utmost importance,” she said. “As we understand it, there are some mechanisms that the FDA could take to ensure the manufacture of teprotumumab without disruption of production of the vaccine.”

Brown noted that there are patients across the country who are in the midst of treatment with the drug, and without that continued treatment their vision could be adversely impacted.

Teprotumumab received FDA approval in 2020 and that could play a factor in how much is available. As the only drug of its kind in the market, the stock is not plentiful.

“We have concerns considering that the FDA in the past has used its authority to prevent drug shortages,” Brown said. “We would hope that they use this precedence”

When the Coronavirus Aid, Relief, and Economic Security (CARES) Act was signed into law on March 25, 2020, lawmakers included a provision amending the drug shortage reporting requirements and creating new requirements related to medical device shortages.

Congress anticipated potential shortfalls with other medications and built language into the CARES Act to guard against these issues. It granted the FDA the ability to thwart shortages.

“Congress directed the FDA to be able to expedite and prioritize applications or inspections that could mitigate or prevent a drug shortage,” Todd said. “The FDA can prioritize to review relevant data and can institute strategies to release individual batches of drugs.”

Over the last 10 months, there has been an increased demand for products used to diagnose and treat COVID-19 patients. This has placed stress on the manufacturing and delivery of vital products, having more information about drug, drug ingredient, and device shortages has been seen as more critical.

The CARES Act expands the scope of drug products subject to notification. Previously, drug manufacturers were required to notify the Food and Drug Administration (FDA) of shortages or expected shortages of drugs that are “life-supporting, life-sustaining, or intended for use in the prevention or treatment of a debilitating disease or condition.”

The FDA notes that it has been closely monitoring the medical supply chain “with the expectation that it may be impacted by the COVID-19 outbreak, potentially leading to supply disruptions or shortages of drug and biologic products in the US,” and adds that notifying the FDA according to this guidance will help the agency to prevent or mitigate shortages.

The FDA added that it maintains public lists of drugs and biologics that are subject to shortages. The list includes the name of the product, the reason for the shortage, and the estimated shortage duration, based on information submitted by the manufacturer. This posted information may also include information that the manufacturer makes available to stakeholders and patients about the shortage.

“It is critical that the treatment is not delayed and is provided without interruption during the active phase,” Todd said. “As an organization dedicated to protecting patients from avoidable vision loss, ensuring patients have access to therapies that can address the devastating and sight-threatening consequences of TED is a significant priority.”

While the group has not heard any anecdotal information from ophthalmologists regarding shortages of teprotumumab, it noted that ophthalmologists are aware of the potential for shortfalls in the supply.

“We have heard from patients who have expressed a concern about the shortage, and are already facing treatment disruption,” Todd said.

Unlike other ophthalmic medications, teprotumumab is in a unique position as a newly approved drug and as a first-of-its-kind treatment option for TED.

“One of the challenges is that some of the other drugs have been out longer and have larger supplies produced,” Todd said. “Teprotumumab, because it is new, does not have the backup supply.”

Going forward, Brown said the organization will take its case to Congress, if necessary.

“We will continue to encourage the FDA to use the authority it has received from Congress to head off any potential shortages,” she concluded.

Amid ramped up production of vaccines, CARES Act gives FDA power to head off potential drug shortfalls. Prevent Blindness is urging the FDA to use its authority to ensure TED treatment drug supply isn’t interrupted. 


As COVID-19 focuses attention on vaccine, medication shortages loom

How ophthalmologists educate themselves

Addressing communication and grading system challenges

Shaily Shah, MD, Northern California Cornea Associates, shares pearls for ophthalmologists on managing ocular toxicities in patients with myeloma. 

Leber hereditary optic neuropathy: Outlining disease’s natural course

As COVID-19 focuses attention on vaccine, medication shortages loom

Managing ocular toxicities in myeloma