With the youngest of the baby boomers hitting 65 by 2029, the number of people with visual impairment or blindness in the United States is expected to double to more than 8 million by 2050, according to projections based on the most recent census data and from studies funded by the National Eye Institute. Another 16.4 million Americans are expected to have difficulty seeing due to correctable refractive errors such as myopia or hyperopia.

The researchers were led by Rohit Varma, MD, director of the University of Southern California’s Roski Eye Institute, Los Angeles, and published their analysis May 19th in JAMA Ophthalmology. They estimate that 1 million Americans were legally blind (20/200 vision or worse) in 2015. Meanwhile, 3.2 million Americans had visual impairment in 2015—20/40 or worse vision with best possible correction. Another 8.2 million had vision problems due to uncorrected refractive error.

“These findings are an important forewarning of the magnitude of vision loss to come,” said NEI Director Paul A. Sieving, MD, PhD. “They suggest that there is a huge opportunity for screening efforts to identify people with correctable vision problems and early signs of eye diseases. Early detection and intervention—possibly as simple as prescribing corrective lenses—could go a long way toward preventing a significant proportion of avoidable vision loss.”

Over the next 35 years, Dr. Varma and his colleagues project that the number of people with legal blindness will increase by 21 percent each decade to 2 million by 2050. Likewise, best-corrected visual impairment will grow by 25 percent each decade, doubling to 6.95 million. The greatest burden of visual impairment and blindness will affect those 80 years or older, as advanced age is a key risk factor for diseases such as age-related macular degeneration and cataract.

The researchers analyzed data on visual impairment and blindness from six large studies: the Beaver Dam Eye Study; Baltimore Eye Survey and Salisbury Eye Evaluation Study; the Chinese American Eye Study; Los Angeles Latino Eye Study; and Proyecto VER. They used the 2014 census and population growth projections to estimate the nationwide prevalence of vision impairment and blindness now and in 2050.

In terms of absolute numbers, non-Hispanic whites, particularly white women, represent the largest proportion of people affected by visual impairment and blindness, and their numbers will nearly double. By 2050, 2.15 million non-Hispanic white women are expected to be visually impaired and 610,000 will be blind. “Based on these data, there is a need for increased screening and interventions across all populations, and especially among non-Hispanic white women,” Dr. Varma said.

African Americans currently account for the second highest proportion of visual impairment, but that is expected to shift to Hispanics around 2040, as the Hispanic population—and particularly the number of older Hispanics—continues to grow. Hispanics have particularly high rates of diabetes, which is associated with diabetic eye disease, a treatable cause of visual impairment.

African Americans, meanwhile, are expected to continue to account for the second highest proportion of blindness. “African Americans are at disproportionately high risk for developing glaucoma, a potentially blinding eye disease that typically causes the loss of peripheral, but not central vision, so people tend to not realize that they are losing their vision and do not seek treatment,” Dr. Varma said.

Avedro Cross-Linking System Gains FDA Nod
Avedro Inc. received approval from the Food and Drug Administration for Photrexa Viscous, Photrexa and the KXL System. Photrexa Viscous and Photrexa are photoenhancers indicated for use with the KXL System in corneal collagen cross-linking for the treatment of progressive keratoconus. Avedro’s Photrexa Viscous, Photrexa and the KXL System represent a first-in-class therapeutic treatment for this sight-threatening indication.

“This approval marks a tremendous milestone for the treatment of progressive keratoconus,” said Brian Roberts, chief operating and financial officer for Avedro. “We’re excited to provide ophthalmologists in the United States with these tools to treat this orphan disease. We thank the FDA for their diligent efforts as we worked towards approval.  We plan to begin taking orders for the KXL System immediately, and plan to begin shipping our Photrexa products in the next few months as we ramp up our drug manufacturing.”

Keratoconus is the most common corneal dystrophy in the United States, affecting approximately one in every 2,000 Americans or approximately 170,000 people in the United States.

“This FDA approval has been highly anticipated by the keratoconus community,” said Mary Prudden, executive director for the National Keratoconus Foundation. “Corneal cross-linking provides patients a much-needed option to treat this debilitating disease. Patients suffering from progressive keratoconus can now receive a therapeutic treatment that has been rigorously tested and approved.”

“I applaud Avedro’s efforts to make this clinically important treatment available to U.S. patients,” said Peter Hersh, MD, of The Cornea and Laser Eye Institute, CLEI Center for Keratoconus, and the clinical study medical monitor. Dr. Hersh added, “In the studies, treated eyes showed improvement in Kmax at 12 months, while in untreated eyes Kmax continued to worsen. The Photrexa formulations and the KXL system represent an invaluable new treatment option for corneal surgeons in the treatment of keratoconus patients.”

Rajesh Rajpal, MD, chief medical officer for Avedro added, “Avedro and I look forward to working with U.S. ophthalmologists to raise awareness of our new FDA-approved treatment for progressive keratoconus.”

The Photrexa formulations and the KXL System are expected to be available for qualifying patients through their ophthalmologists before the end of this year.

RAS Reverses Some Effects of DR In Mouse Model
In a first of its kind report, a study in the American Journal of Pathology describes a potential new intraocular treatment based on manipulating the renin angiotensin system (RAS) that both prevents and reverses some characteristics of diabetic retinopathy in a mouse model.

“We are not aware of another study that has demonstrated a therapy capable of reversing this form of retinal pathology, particularly in the presence of persistent untreated hyperglycemia,” commented lead investigator Maria B. Grant, MD, of the Eugene and Marilyn Glick Eye Institute of Indiana University, Indianapolis.

“This research is based on the hypothesis that an imbalance between two axes of the RAS is a key initial event that leads to development of diabetic microvascular complications,” explained Dr. Grant. The two axes consist of the classic and vasoprotective RAS. The proinflammatory, vasoconstrictive classical RAS component is normally kept in check by a vasoprotective axis that is both anti-inflammatory and vasodilatory. Angiotensin converting enzyme-2 (ACE-2) is the primary enzyme of the vasoprotective component. Administration of AAV-ACE--the therapeutic agent under evaluation—directly into the vitreous cavity of the eye using an adeno-associated virus vector, increases ACE-2 expression.

Investigators used mice, some of which were injected with streptozotocin (STZ) to induce diabetes. The protective effects of AAV-ACE2 were examined by performing two sets of experiments. In one cohort, AAV-ACE2 was administered two weeks prior to STZ injection. In a second cohort, to evaluate whether the enhanced expression of ACE2 could reverse diabetic retinopathy, AAV-ACE2 was administered six months after STZ, when diabetes and retinopathy were already established.

The investigators found that both strategies effectively decreased the numbers of proinflammatory cells present in the diabetic retina. Leukostasis—abnormal aggregation and clumping of white blood cells within blood vessels—was only seen in diabetic animals receiving control injections. In addition, using a histological endpoint of retinal vascular degeneration, called acellular capillaries, the group determined that the AAV-ACE2 injection could reverse the diabetes-induced pathology. “These findings are very exciting because it is traditionally believed that this endpoint of vascular degeneration, acellular capillaries, represents an irreversible lesion,” emphasized Dr. Grant.

One strength of this experimental approach is that intravitreal administration eliminates the problem of the blood-retinal barrier interfering with access of systemically administered therapeutic agents. The investigators envision that inducing ACE2 overexpression to improve vascular characteristics and decrease inflammation may be translatable to other vascular diseases such as stroke, kidney disease and heart disease.

ARMOR Again Shows High Levels Of Resistance
Bausch + Lomb announced preliminary 2015 results of the ARMOR (Antibiotic Resistance Monitoring in Ocular MicRoorganisms) surveillance study, the only multicenter, nationwide survey of antibiotic resistance patterns specific to eye care, at the 2016 Association for Research in Vision and Ophthalmology Annual Meeting in Seattle. Researchers also presented data that examined resistance profiles of common bacterial pathogens isolated from the aqueous and vitreous humor to antibiotics routinely used in ophthalmic practice.

In the first study, ARMOR researchers reported comparisons of susceptibility rates available from surveillance in 2015 to results from 2014. At the time of the analysis, a total of 441 isolates of Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Pseudomonas aeruginosa and Haemophilus influenzae, organisms frequently implicated in bacterial eye infections, were collected from 19 sites across the United States. The isolates were then tested for susceptibility to as many as 15 antibiotics.

Similar to previous years, study authors reported that surveillance data continue to show high levels of antibiotic resistance among staphylococcal isolates, especially among methicillin-resistant strains, with many demonstrating multidrug resistance. Resistance among the staphylococci was most notable for azithromycin (54 to 59 percent) oxacillin/methicillin (24 to 45 percent), and ciprofloxacin (22 to 28 percent), while CoNS isolates also exhibited high levels of non-susceptibility to tobramycin (19 percent) and trimethoprim (26 percent). In 2015, 20 percent of S. aureus isolates and 39 percent of CoNS isolates were non-susceptible to three or more drug classes, with multidrug resistance remaining prevalent among MR S. aureus (67 percent) and MRCoNS (74 percent). Isolates of S. pneumoniae remained susceptible to fluoroquinolones and chloramphenicol, while non-susceptibility to azithromycin and penicillin was 50 percent and 38 percent, respectively. Resistance among P. aeruginosa isolates continues to be low, while H. influenzae isolates were generally susceptible to all antibiotics tested.

“These latest data demonstrate that resistance of common ocular pathogens to several commonly used antibiotics continues to be a challenge,” said Penny Asbell, MD, lead ARMOR study author, professor of ophthalmology at Icahn School of Medicine at Mount Sinai, and director of the Cornea Service and Refractive Surgery Center at the Mount Sinai Hospital. “Understanding antibiotic resistance patterns is critical for the selection of effective agents to treat potentially sight-threatening ocular infections. The ARMOR data allow physicians to select agents that have proven efficacy and a broad spectrum of activity.”

In a second study, investigators examined antibiotic resistance profiles of 172 aqueous and vitreous humor isolates collected between 2009 and 2015 through the ARMOR surveillance study, including 30 S. aureus, 100 CoNS, 21 S. pneumoniae, 10 P. aeruginosa and 11 H. influenzae. Similar to the preliminary 2015 ARMOR findings, researchers reported that antibiotic resistance was prevalent among staphylococcal isolates, particularly CoNS, with many demonstrating multidrug resistance.

Further Eye Issues Seen in Zika Babies
Researchers studying babies with a Zika virus-related birth defect say they have found previously unreported eye problems possibly linked to the virus that could result in severe visual impairment. In three Brazilian infants with microcephaly, the researchers observed retinal lesions, hemorrhaging and abnormal blood vessel development not noted before in relation to the virus. The findings were published online in Ophthalmology.

A prior study of 29 Brazilian babies with presumed congenital Zika infection showed that a third had eye problems. These included ocular lesions, optic nerve abnormalities and chorioretinal atrophy, a withering of the retina and choroid, the latter of which provides oxygen and nutrients to the retina.

For this case study, ophthalmology researchers from Brazil and Stanford University examined the eyes of three infant boys from northern Brazil born in late 2015 with microcephaly. All had mothers with suspected Zika virus infections during the first trimester of pregnancy.

Among the findings, the researchers identified several types of ocular issues not previously observed in relation to Zika virus, some of which could cause visual impairment if untreated. These included: hemorrhagic retinopathy; abnormal vasculature in the retina, including signs of missing blood vessels in the retina where the cells may have died; and torpedo maculopathy. In addition to these observations, the infants in this study also exhibited other ocular symptoms noted in the previous study. Specifically, all three babies in this case study showed signs of pigmentary maculopathy, lesions that appear as speckles of pigment on the macula. Four eyes had symptoms of chorioretinal atrophy marked by a darkly pigmented ring.

The study is small with limited observational data. However, the findings add to a growing body of clinical information about how the Zika virus may affect children’s eye development and vision. The authors noted that it remains unclear whether the viral infection itself causes eye abnormalities or if they are a consequence of Zika-induced microcephaly.  REVIEW