Researchers at Massachusetts Eye and Ear/Harvard Medical School and the University of Crete have conducted a Phase I/II clinical trial investigating the efficacy of statins for the treatment of patients with the dry form of age-related macular degeneration. Although effective treatments are available for the wet form of AMD, they are currently lacking for the more prevalent dry form. The researchers found evidence that treatment with high-dose atorvastatin (80 mg) is associated with regression of lipid deposits and improvement in visual acuity, without progression to advanced disease, in high-risk AMD patients. Their findings were published in EBioMedicine—a new online journal led by editors of the journals Cell and The Lancet—and not only further the connection between lipids, AMD and atherosclerosis, but also present a potential therapy for some patients with dry AMD.

“We found that intensive doses of statins carry the potential for clearing up the lipid debris that can lead to vision impairment in a subset of patients with macular degeneration,” said Joan W. Miller, MD, the Henry Willard Williams Professor and chair of ophthalmology at Harvard Medical School and chief of ophthalmology at Massachusetts Eye and Ear and Massachusetts General Hospital. “We hope that this promising preliminary clinical trial will be the foundation for an effective treatment for millions of patients afflicted with AMD.”

Ophthalmologists and vision researchers have long suspected that there may be a connection between dry AMD and atherosclerosis. In dry AMD, physicians often see soft, lipid-rich drusen in the outer retina, similar to the buildup of lipid material in the inner walls of blood vessels in atherosclerosis. Statin use is widespread in middle-aged and older individuals, who also have an increased risk of AMD; however, previous studies have shown very little correlation between regular statin use and improvements in AMD. The authors of the EBioMedicine paper hypothesized that, due to the heterogeneous nature of the disease, patients with soft, lipid-rich drusen may respond better to statins prescribed at higher dosages.

“Not all cases of dry AMD are the exactly the same, and our findings suggest that if statins are going to help, they will be most effective when prescribed at high dosages in patients with an accumulation of soft, lipid material,” said Demetrios Vavvas, MD, PhD, a clinician scientist at Mass Eye and Ear and co-director of the Ocular Regenerative Medicine Institute at Harvard Medical School. “These data suggest that it may be possible to eventually have a treatment that not only arrests the disease but also reverses its damage and improves the visual acuity in some patients.”

Eye Abnormalities Tied to Zika Virus in Infants
Vision-threatening eye abnormalities in infants in Brazil with microcephaly may be associated with presumed intrauterine infection with Zika virus, according to a study published online by JAMA Ophthalmology.

An epidemic of Zika virus has been happening in Brazil since April 2015. Six months after the onset of the Zika virus outbreak, there was an unusual increase in newborns with microcephaly. In January 2016, the Brazilian Ministry of Health reported 3,174 newborns with microcephaly.

Rubens Belfort Jr., MD, PhD, of the Federal University of São Paulo, Brazil, and coauthors evaluated the ocular findings of 29 infants with microcephaly (head circumference less than or equal to 32 centimeters) with a presumed diagnosis of congenital Zika virus. The study was conducted during December 2015 and all the children and their mothers were evaluated at the Roberto Santos General Hospital, Salvador, Brazil.

Of the 29 mothers, 23 (79.3 percent) reported suspected Zika virus signs and symptoms during pregnancy, including rash, fever, arthralgia (joint pain), headache and itch. Among the 23 mothers who reported symptoms during pregnancy, 18 or 78.3 percent reported Zika virus symptoms during the first trimester of pregnancy, according to the report.

Abnormalities of the eye were observed in 10 of the 29 infants (34.5 percent) with microcephaly; of the 20 eyes in 10 children, 17 eyes (85 percent) had ophthalmoscopic abnormalities. Bilateral abnormalities were found in seven of the 10 infants (70 percent) presenting with ocular lesions, the most common of which were focal pigment mottling of the retina and chorioretinal atrophy in 11 of the 17 eyes with abnormalities (64.7 percent). There also were optical nerve abnormalities in eight eyes (47.1 percent), along with other findings.

“This study can help guide clinical management and practice, as we observed that a high proportion of the infants with microcephaly had ophthalmologic lesions,” the authors wrote. “Infants with microcephaly should undergo routine ophthalmologic evaluations to identify such lesions. In high-transmission settings, such as South America, Central America and the Caribbean, ophthalmologists should be aware of the risk of congenital ZIKV-associated ophthalmologic sequelae.”

Twenty-three patients with dry AMD marked by soft lipid deposits in the outer retina were prescribed a high dose (80 mg) of atorvastatin (Lipitor) and several generic equivalents. Of the 23 patients, 10 experienced an elimination of the deposits under the retina and mild improvement in visual acuity. Other techniques that have attempted to eliminate the deposits have mostly failed with the disease continuing to progress to more advanced dry AMD or a conversion to the wet form of AMD.

As the next step for this line of research, the investigators plan to expand to a larger prospective multicenter trial to further investigate the efficacy of the treatment in a larger sample of patients with dry AMD.
“This is a very accessible, FDA-approved drug that we have tremendous experience with,” said Dr. Vavvas. “Millions of patients take it for high cholesterol and heart disease, and based on our early results, we believe it offers the potential to halt progression of this disease, but possibly even to restore function in some patients with dry AMD.”

Too Much Screen Time and Too Little Sunlight
The largest study
of childhood eye diseases ever undertaken in the United States confirms that the incidence of childhood myopia among American children has more than doubled over the last 50 years. The findings echo a troubling trend among adults and children in Asia, where 90 percent or more of the population have been diagnosed with myopia, up from 10 to 20 percent 60 years ago.

The Multi-Ethnic Pediatric Eye Disease Study (MEPEDS), conducted by researchers and clinicians from the USC Eye Institute at Keck Medicine at USC in collaboration with the National Institutes of Health, adds to a growing body of research into the incidence and potential causes of myopia, or near-sightedness, in children and adults.

The possible culprit? Too much “screen time” and not enough sunlight, according to Rohit Varma, MD, MPH, and director of the USC Eye Institute.

“While research shows there is a genetic component, the rapid proliferation of myopia in the matter of a few decades among Asians suggests that close-up work and use of mobile devices and screens on a daily basis, combined with a lack of proper lighting or sunlight, may be the real culprit behind these dramatic increases,” said Dr. Varma. “More research is needed to uncover how these environmental or behavioral factors may affect the development or progression of eye disease.”

The USC study found that the incidence of childhood myopia in the United States is greatest in African-American children, followed by Asian-American children, Hispanic/Latino and non-Hispanic white children. Future research may include re-examining the MEPEDS cohort to evaluate how widespread use of “screens” and other environmental or behavioral factors may be affecting the progression of childhood myopia and other eye diseases over time.

From 2003 through 2011, MEPEDS provided free eye exams at USC Eye Institute clinics to more than 9,000 Los Angeles-area children ages 6 months through 6 years. To date, data from the USC study has generated more than 20 academic papers on the prevalence of childhood eye diseases, including myopia, hyperopia, amblyopia and strabismus.

Shire Resubmits Lifitegrast NDA
Shire announced that
it resubmitted the New Drug Application to the  Food and Drug Administration for its investigational candidate, lifitegrast, for the treatment of dry-eye disease. Shire resubmitted the NDA in response to the complete response letter the company received from the FDA on October 16, 2015.

Addressing the FDA request for an additional study, Shire included in its NDA resubmission package data from OPUS-3, a Phase III efficacy and safety trial with a primary endpoint of patient-reported symptom improvement. The resubmission package also included information requested by the FDA regarding product quality.

“The NDA for lifitegrast now includes data from five randomized controlled clinical trials, with more than 2,500 patients, making it the largest data set for an investigational stage compound in dry-eye disease to date,” said Philip J. Vickers, PhD, head of Research & Development at Shire. “Because we believe that, if approved, lifitegrast has the potential to help the millions of U.S. adults living with symptoms of dry-eye disease, we worked diligently to submit our response to the CRL as quickly as possible.” The FDA has 30 days after resubmission of an NDA to acknowledge receipt and determine if the submission is a complete response. Upon acceptance, the FDA will provide Shire with a PDUFA date anticipated to be within six months of the date of submission.  REVIEW