Quick Hits

Florida ophthalmic society readies for Zika

Group is writing steps for dealing with the virus.

By Jennifer Kirby, PentaVision editor

With its tropical climate and close association to South America, it makes perfect sense that (as of this writing) Florida leads the country in travel-associated Zika virus cases (405) and has, thus far, been identified as the only state with mosquito-borne local transmissions (14). Given these facts, along with data showing the virus has ocular manifestations, what, if any, protocols have Florida ophthalmologists established that their peers elsewhere can emulate?

“If a patient presents with any of the systemic symptoms of the virus, such as fever, headache, muscle and joint pain, and also exhibits the ocular manifestations, such as nonpurulent conjunctivitis, we refer the patient to his or her general practitioner for further virus assessment, which includes blood work to confirm the presence of the virus,” explains Joseph Nezgoda, MD, MBA, speaking on behalf of the Florida Society of Ophthalmology. The CDC says a urine test can also confirm a Zika infection. Physicians should continue to follow patients in case the virus’ ocular manifestations appear along with the conditions, continues Dr. Nezgoda.

“For practitioners in states where the virus is travel-associated, obviously, you want to ask patients whether they’ve recently been in South America,” he says.

In addition to nonpurulent conjunctivitis, focal pigment mottling of the retina, chorioretinal atrophy, optic nerve abnormalities, bilateral iris coloboma, lens subluxation, loss of the foveal reflex and well-defined macular atrophy is noted in infants who inherit the virus in utero.

However, it is unclear whether these findings are due to the virus’ hallmark clinical sign of microcephaly in infants or the virus itself, according to the American Academy of Ophthalmology. NEJM reports in its June issue that uveitis has been linked to the Zika virus in a man in his early 40s.

“The first papers on the Zika virus and its ocular manifestations were only published within the last couple months, and I’m sure more data will come out,” explains Dr. Nezgoda.

“The Florida Society of Ophthalmology plans on incorporating all the findings into the medical education we offer members, so we can continue to provide the best care for all our patients. Certainly this will be a hot topic at our next meeting and, obviously, we want to do whatever we can to play a role in the fight against the virus.” OM

ZIKA VIRUS OVERVIEW

Transmission: Mosquito bites, in utero, sex and, theoretically, blood transfusion.

Case counts: Nationwide, 2,246 travel-associated cases and in Florida, 14 mosquito-borne cases, as of late August.

Symptoms: Fever, headache, rash, joint and muscle pain and ocular issues, such as conjunctivitis. Symptoms can last up to a week, and hospitalizations are rare. The Zika virus can trigger Guillain-Barre syndrome, which causes a person’s immune system to damage his or her own nerve cells, inducing muscle weakness and, sometimes, paralysis.

Action plan: The National Institute of Allergy and Infectious Diseases, part of the NIH, began a clinical trial of a vaccine to prevent the virus. Roughly 80 healthy subjects, ages 18 to 35, will participate in the trial at three U.S. study sites.

Omega-3s linked to reduced osmolarity

Nutritional supplements are also found to improve MMP-9, OSDI scores.

By Robert Stoneback, associate editor

Oral consumption of re-esterified omega-3 fatty acids can help reduce tear osmolarity, according to a study recently published in Cornea.

“The findings here are game changing,” according to Alice T. Epitropoulos, MD, lead investigator of the study.

Subjects tested had been diagnosed for dry eyes and meibomian gland dysfunction. They were randomly divided into two groups, with 54 receiving PRN Dry Eye Omega Benefits and 51 receiving a placebo. This was a multicenter, double-masked, prospective, interventional study.

The patients receiving PRN achieved a statistically significant improvement in tear osmolarity, omega index levels, a more stable tear film and decreases in ocular cytokine biomarker and ocular symptoms, according to Dr. Epitropoulos.

Subjects were evaluated three times over the course of 12 weeks ­— once at baseline, once at week six and once at week 12. A statistically significant reduction in tear osmolarity was observed in the omega-3 group at weeks six (−16.8 ± 2.6 vs. −9.0 ± 2.7 mOsm/L, P = 0.042) and 12 (−16.8 ± 2.6 vs. −9.0 ± 2.7 mOsm/L, P = 0.042).

“Up until recently, we really didn’t know the extent of ocular benefits in taking omega-3 nutritional supplements, but the most recently published research has brought its usefulness to the forefront,” says Dr. Epitropoulos. The average American is deficient in marine source omega-3s, she adds.

“This study really changes the way that we manage DED and MGD,” continues Dr. Epitropoulos. “The results support a specific dose response and should be included as a primary therapy when managing the ocular surface and adjuvant therapy in the perioperative milieu for cataract and refractive surgery.” OM

Dr. Epitropoulos is a consultant and adviser for PRN.

HORV task force: Use vancomycin at own discretion

Rare, blinding condition described as “hypersensitive reaction” to the antibiotic.

By Robert Stoneback, associate editor

While but a few cases of a rare, sight-threatening condition have been reported, their existence has sent significant ripples through the ophthalmic community.

The condition, known as hemorrhagic occlusive retinal vasculitis (HORV), has been linked to vancomycin, according to a joint ASCRS and ASRS task force.

This clinical alert states that data have been collected on 36 eyes belonging to 22 patients who have been diagnosed with HORV based on clinical history and fundus imaging. All but one case took place in the United States; the other occurred in Australia. Of those 22 patients, 12 were diagnosed in 2015-2016, five in 2013-2014 and five prior to 2013. All received intraocular vancomycin, although there is no known association with a specific formulation or manufacturer. HORV can follow any intraocular procedure, usually cataract surgery.

Of the 36 eyes with HORV, 22 were 20/200 or worse and eight were blind, according to the clinical alert. Seven of the eyes received an additional bolus of intravitreal vancomycin, for treatment of presumed bacterial endophthalmitis. Of those seven eyes, five were blind at their most recent follow-up.

The task force has not recommended that physicians cease using the drug, though one member of the task force, David F. Chang, MD.

Dr. Chang, a member of the ASCRS Cataract Clinical Committee, describes HORV as most likely a rare type III hypersensitivity reaction to intraocular vancomycin. There is no relation between HORV and age, gender or specific patient characteristics, he says.

Risks and benefits

Dr. Chang, in a phone interview, said that surgeons, now equivocal about the use of intracameral vancomycin prophylaxis, must weigh the risk of HORV against vancomycin’s benefits, such as hypothetical superiority against MRSA.

Dr. Chang had been using intracameral vancomycin prophylaxis routinely for 18 years and never had a patient with HORV, or other vancomycin-related complications, of which he is aware. Based on the recent task force findings, though, he has decided to switch to compounded moxifloxacin for routine intracameral prophylaxis.

Dr. Chang considers HORV to be “the single worst complication” that can occur with cataract surgery. It can lead to blindness in both eyes because of its delayed onset.

Even rarer than endophthalmitis

Jeffrey Liegner, MD, of Eye Care Northwest, NJ, says he has never had a case of HORV at his clinic. He uses Imprimis Pharmaceuticals’ Tri+Moxi+Vanc on the more than 1,000 eyes who undergo cataract surgery per year at Northwest. He plans to keep using the drug, and notes the importance of its triamcinolone, a steroid that helps suppress hypersensitization in patients.

Dr. Liegner says cataract surgery is performed about 3 million times each year, and with only 36 eyes affected by HORV that makes it more rare than endophthalmitis.

John Saharek, chief commercial officer of Imprimis Pharmaceuticals, says his company “has not received any reported adverse events” with regard to its vancomycin formulations.

Each batch of ophthalmic injectable formulations that Imprimis compounds is sent to labs for sterility and endotoxin testing, Mr. Saharek adds.

Approvals and registries

A spokesperson for the FDA’s Center for Drug Evaluation and Research said the organization is aware of the cases of HORV and the clinical alert. When using intravitreal vancomycin as a prophylaxis for endophthalmitis, the agency advises it only be used in an approved manner, following all labeled instructions. The FDA encourages the reporting of all suspected adverse events to its MedWatch system, regardless of whether the intended use is on label or off label.

The compounding pharmacy Avella was also contacted for this story; it declined to comment.

A registry for the confidential reporting of HORV cases has been set up, which can be accessed through the home pages of the ASCRS or ASRS website.

It is likely that more cases of HORV will be reported in the future now that more ophthalmologists are aware of the complication and are able to diagnose it, says Dr. Chang. “This is why it is important to maintain a registry to learn as much as possible about this problem.” OM

A first-hand experience with HORV

A retinal physician recalls treating a patient who lost her sight in one eye to an ‘unknown clinical entity.’

By Robert Stoneback, Associate Editor

More than five years ago, Robert Engstrom, Jr., MD, of the California clinic The Retina Partners, had a close look at hemorrhagic occlusive retinal vasculitis before it became known as HORV.

Then, this sight-threatening condition was called an “unknown clinical entity.”

Dr. Engstrom’s female patient was referred to him after an uneventful cataract extraction with intraocular lens implant. Dr. Engstrom recalls that she had profound darkening of vision, a mild to moderate vitritis and severe vascular sheathing, primarily in her retinal periphery. This was associated with blotchy retinal hemorrhages, reminiscent of a venous stasis retinopathy picture.

This patient became part of the initial case series describing the clinical features of the newly recognized HORV syndrome. This report of 11 eyes, from six patients, was conducted by Andre Witkin, MD, of Tufts University and published in Ophthalmology in 2015. Dr. Engstrom also assisted in the research. All the patients had uncomplicated cataract surgery and had received intracameral vancomycin for prophylaxis against endophthalmitis. They were treated with topical corticosteroids. Some patients received additional treatment, such as antiviral medication, intravitreal antibiotics and pars plana vitrectomy, according to the study.

The second eye

“My patient’s second eye involvement occurred three years after her first eye, clearly linking this as an immune reaction, rather than a toxic one,” recounts Dr. Engstrom. His patient was the only one in this study with a three-year time frame between involved eyes.

The patient’s second eye received no supplemental vancomycin due to the poor outcome of the first eye. She also received Avastin (bevacizumab, Genentech) for treatment of neovascular glaucoma, and panretinal photocoagulation.

Despite these difficulties, she had the best visual outcome of those involved in the report, he says. The study listed her as having 20/50 vision in one eye, and loss of vision in the other.

According to the study, final visual acuity was less than 20/100 in 8 of the 11 eyes tested. One patient went blind in both eyes. One eye had 20/60 vision; this patient had 20/150 vision in her other eye.

Patients with HORV manifest with profound vision loss typically described as a darkening of vision, which is sometimes associated with central blurring and floaters, says Dr. Engstrom.

Dr. Engstrom advises that there can be a delay in the onset of HORV symptoms up to 14 days from surgery.

“The delay in onset of symptoms is important in planning the fellow eye surgery which would ideally be at least 2 weeks after the patient’s first eye,” Dr. Engstrom says. “Patients should be asked in the pre-op area regarding any new vision complaints in their first eye prior to fellow eye surgery, and a dilated exam performed if necessary, especially if vancomycin is used routinely during cataract extraction.”

The ASCRS and ASRS recently issued a clinical alert regarding HORV, a rare condition that has been linked to patients treated with vancomycin. A HORV task force says that the condition is most likely a rare Type III hypersensitivity to vancomycin. A total of 22 patients have been diagnosed with HORV so far.