Jennifer DiSanto

Results of a recent study indicate that intravitreal injection of bevacizumab generally causes an increase in intraocular pressure (IOP), which then decreases 30 minutes post-intravitreal injection. Researchers concluded this increase in pressure is tolerable to the corneal endothelium and safe for most patients’ eyes.

Author Myungwon Lee, MD, of the Department of Ophthalmology, College of Medicine, Dankook University, Cheonan-si, Republic of Korea, told MD Magazine, “I think an acute increase of IOP happened by the acute increase of vitreous volume in limited eyeball space.”

The research team looked at 42 patients who received an intravitreal injection of 2.5 mg/0.1 mL bevacizumab to treat central serous chorioretinopathy or diabetic macular edema. Changes in IOP, corneal endothelial cells and corneal thickness were examined prospectively with a specular microscope at baseline, 2 minutes, 5 minutes, and 30 minutes post-injection.

The patient population included 18 males and 24 females with a mean age of 57.81 years (± 14.11). There were 13 eyes with diabetes mellitus (31%), and 5 eyes with a history of cataract surgery (11%). Eleven patients had at least an eye with branch retinal vein occlusion. Ten eyes had age-related macular degeneration (AMD), 7 had proliferative diabetic retinopathy, 6 had central retinal vein occlusion, 5 had central serous chorioretinopathy, and 3 had with diabetic macular edema (DME). All 42 eyes were receiving an injection for the first time.

According to the published results, at baseline, the mean IOP for patients was 11.48 ± 2.22 mmHg. At 2 minutes, the mean IOP increased to 49.71 ± 10.73 mmHg, the at 5 minutes decreased slightly to 37.64 ± 11.68 mmHg. By the 30-minute mark, mean IOP had returned to 14.88 ± 4.77 mmHg, essentially normal, in all patients. Changes were considered statistically significant (P < 0.01).

In only 1 eye studied, IOP did not decrease to ≤30 mmHg even at 30 min after injection.

“According to changes in IOP with time, the coefficient of variation of the corneal endothelium significantly increased (P = 0.03), but cell density, hexagonality of the corneal endothelium, and central corneal thickness did not change (p = 0.79, 0.21, and 0.08, prospectively),” Lee and colleagues wrote. A week after the injection, there was no sign of inflammation or any other complications in all eyes studied.

Prior to the study, patients were given a complete eye exam, including visual acuity tests, slit-lamp, and fundus exams, as well as optical coherence tomography pre- and post-injection. They also received topical antibiotics between measurements and applied a patch with ofloxacin ointment after the last follow-up.

The authors said their study was the first to observe this change in corneal endothelial cells following the post- bevacizumab injection IOP increase. During the IOP increase and subsequent decrease, they wrote, “endothelial cells may receive momentary compression and stretch pressure, but it is tolerable and has no harmful effects on the corneal endothelium.”

“Acute increase of IOP did not affect corneal endothelial cells, though CV (coefficient of variation) temporarily changed in high IOP,” Lee said. “I think the coefficient of variation of the cell area was affected by mechanical stretching by an acute increase of IOP.”

The study, “Short-term effects and safety of an acute increase of intraocular pressure after intravitreal bevacizumab injection on corneal endothelial cells,” was published in 

This article was originally published by 

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Increase in intraocular pressure found to be tolerable to the corneal endothelium and safe for treating central serous chorioretinopathy or diabetic macular edema.

Bevacizumab Intravitreal Injection Intraocular Pressure Found Safe, Tolerable

In an effort to make HIV treatment easier for patients, a study recently compared the safety and efficacy of dolutegravir to that of combination antiretroviral therapy (ART). 

Researchers hypothesized that fewer drugs for maintenance may reduce the incidence of treatment-related adverse events, as well as reducing costs and pill burden. Combination ART regimens were deemed effective. However, increased virologic failure and drug resistance following dolutegravir monotherapy led researchers to recommend against its use.

DOMONO, an open-label, phase 2 trial, assessed the non-inferiority of dolutegravir monotherapy to combination ART for maintenance of virologic suppression in patients with HIV-1 infection who had been treated successfully with combination ART. Upon enrollment, a group of 51 patients switched immediately to monotherapy with dolutegravir. A second group of 53 patients were switched after a 24 week delay, during which they received continued treatment with combination ART.

After 24 weeks, 2% of the patients who immediately switched to monotherapy had plasma HIV RNA loads of 200 copies/mL or higher (2% difference; 95% CI, —5 to 12). No difference was observed in the delayed switch group.

At week 48, virologic failure occurred in 8% of the 95 patients who were still receiving dolutegravir monotherapy — 6 were from the group that switched immediately, and 2 from the group who delayed the switch.

Three of the patients who had virologic failure also showed resistance mutation in the integrase gene, leading the research team to discontinue the study early. At the study’s outset, the team decided to stop the study early if more than 2 patients exhibited resistance, and if more than 20 patients had monotherapy failure.

The research team wrote: “Because all 8 patients with virologic failure achieved resuppression of the plasma viral load soon after reinitiation of combination ART, this observation alone would not contraindicate dolutegravir monotherapy. However, the results of integrase sequencing at the time of virologic failure clearly showed that dolutegravir monotherapy cannot replace combination ART, even in patients with a CD4 nadir above 200 cells per L and an HIV RNA zenith of less than 100,000 copies per mL.”

“There is interest in simplification of combination ART for use in maintenance therapy, with no cure for HIV on the horizon," research fellow Janine M. Trevillyan, MBBS, FRACP, and Jennifer F. Hoy, MD, Professor of Infectious Diseases and Director of HIV Medicine at Alfred Hospital and Monash University, in Melbourne, Australia, wrote in a 

 published October 26. "Treatment with combination ART is lifelong and leads to a near-normal life expectancy in most patients. To maintain durable virologil suppression, combination ART needs to be taken reliably. Pill burden, toxicity, and cost have stimulated investigation of simpler maintenance regimens.”

“With substantial risk of harm and minimal evidence of benefit, little justification exists for ongoing investigation of monotherapy strategies,” Trevillyan and Hoy continued. “The focus must now switch to the more promising dual-therapy options (such as dolutegravir and lamivudine or rilpivirine), for which large, randomized trials are underway.”

Dolutegravir as maintenance monotherapy for HIV: a phase 2, randomized non-inferiority trial

Increased virologic failure and drug resistance following dolutegravir monotherapy prompt researchers to recommend against its use in patients with HIV.

HIV Monotherapy Shows Substantial Risk of Harm

According to new data from a quality improvement study, 

 experienced no diabetes-related readmissions, urgent care visits, or emergency department visits within 30 days of hospital discharge when their healthcare providers used Glytec’s eGlycemic Management System to guide 

Researchers at Eastern Virginia Medical School conducted the study and presented their findings earlier this month at the 

“The primary focus of this project was the transition from hospital to home for patients with diabetes,” principal investigator Jagdeesh Ullal, MD, MS, an associate professor at Eastern Virginia Medical School and endocrinologist at Sentara Healthcare told 

. “What we have seen as ‘usual care’ is that most inpatient providers will discharge patients on the same insulin regimen as they were on prior to hospitalization, which means about 70% of these patients have no change to their diabetes therapy even though their average blood glucose on admission is outside the normal range and the nature of their condition on discharge really does necessitate a change.”

Ullal explained that in many cases, the provider feels a level of discomfort in making alterations to home insulin regimens, especially for patients that have only been in their care during a hospital stay.

“They prefer to leave those changes to the primary care providers. Some inpatient providers just don’t see themselves as having sufficient expertise in insulin management and titration,” he said. “As a result, insulin dosing at discharge is often overlooked or not addressed appropriately. However, an improper insulin regimen following hospitalization can set the stage for worsening hyperglycemia, episodes of hypoglycemia, and it can significantly increase the risk of readmission or emergency department visits.”

The study group consisted of 28 patients with 

 with admission A1C >6.5% (average at 9.5%), indicating their diabetes was poorly controlled before hospitalization. Their average blood glucose at admission was 223 mg/dL — 43 mg/dL higher than the normal range.

Researchers managed intravenous (IV)/subcutaneous insulin administration using the Glucommander module of Glytec’s eGlycemic Management System, which provides personalized dosing recommendations and is integrated with the electronic health record (EHR). Patients’ average daily blood glucose during the study was 152 mg/dL, down from 71 mg/dL, or 32%, from the average admission blood glucose, and below the goal range (140-180 mg/dL).

Certified diabetes educators contacted the study patients once a week for the first month after discharge to check on their health and home care. Using the home insulin regimen guided by Glytec’s H2H module, none of the patients had a readmission, urgent care visit, or emergency department visit caused by diabetes or any glucose-related incidents. Only one patient had an episode of severe hypoglycemia (<40 mg/dL).

“We had already been using Glytec’s Glucommander software for IV and subcutaneous insulin dosing during the hospital stay. Several of our prior studies have shown marked reductions in complications, length of stay, hypoglycemia, hyperglycemia, average daily blood glucose, and other measures of good glycemic control—which makes for faster recovery and overall better health,” Ullal said. “By using Glytec’s Hospital-to-Home software in conjunction with Glucommander, we are able to maintain good glycemic control outside of the hospital and avoid diabetes-related readmissions and emergency department or urgent care utilization.”

The study was conducted at Sentara Norfolk General Hospital, Sentara Virginia Beach General Hospital, and Sentara Northern Virginia Medical Center.

Advances in technology can guide insulin regimens prescribed at discharge among patients with diabetes.