The Real-World Effect of Intravitreous Anti-Vascular Endothelial Growth Factor Drugs on Intraocular Pressure: An Analysis Using the IRIS Registry.

PURPOSE: To identify sustained differences in intraocular pressure (IOP) after intravitreous injections of anti-vascular endothelial growth factor (VEGF) drugs. DESIGN: Database study. PARTICIPANTS: Patients seeing an ophthalmic provider who contributes to the database. METHODS: We identified a total of 23 776 unique patients who received only a single type of anti-VEGF medication (bevacizumab, aflibercept, or ranibizumab) by injection in the right eye in the American Academy of Ophthalmology Intelligent Research in Sight Registry. Subgroups included patients with age-related macular degeneration only and patients who had not received an anti-VEGF injection for at least 1 year before the study. We examined those with at least 12, 18, and 25 injections for each of these 3 medications. For all groups, we used fellow, untreated eyes for comparison. MAIN OUTCOME MEASURES: The mean change in IOP from baseline at a minimum of 1 year of follow-up and the proportion of eyes with a clinically significant IOP increase (defined as sustained rise of at least 6 mmHg to an IOP of more than 21 mmHg). RESULTS: All patients in all groups receiving all drugs showed a decrease in IOP from baseline, with a mean of 0.9 mmHg in treated eyes compared with an average decrease of 0.2 mmHg in fellow untreated eyes, a statistically significant difference. A generalized linear model accounting for confounders associated bevacizumab with slightly less lowering of IOP than aflibercept and ranibizumab in most subgroups. A clinically significant IOP increase was seen in 2.6% of eyes receiving injections compared with 1.5% in the associated untreated fellow eyes. Clinically significant IOP increases occurred at a rate of 1.9%, 2.8%, and 2.8% for aflibercept, ranibizumab, and bevacizumab, respectively, which was significantly higher than untreated fellow eyes for bevacizumab and ranibizumab, but not for aflibercept. CONCLUSIONS: These analyses from real-world data indicate that anti-VEGF intravitreous injections are associated with a small but statistically significant decrease in IOP over time. A proportion of patients, on average 2.6%, experienced a sustained clinically significant IOP rise with these drugs overall compared with 1.5% in the fellow untreated eyes. However, such an increase was not seen with aflibercept.

OUTCOMES OF AN INTRAVITREAL INJECTION CLINIC.

PURPOSE: To examine the safety outcomes of an intravitreal injection-only clinic where patients needing long-term anti-vascular endothelial growth factor therapy are treated with injections at a predetermined interval for a set number of injections without an accompanying clinic visit. METHODS: This is a retrospective chart review of all patients with exudative macular degeneration treated in an intravitreal injection clinic over a 4-year period. Data on the outcome measures of interest were gathered from electronic medical records. RESULTS: There were 556 patients who received 4,386 injections in the injection-only clinic in a total of 1,524 injection cycles. One hundred six cycles were interrupted. The most common causes for interruption were decreased vision in the injected eye (32), decreased vision in the fellow eye (23), flashing lights (6), pain (5), and irritation in the noninjected eye (2). Of patients who had interruption of the cycle, 32 had a new diagnosis (6 corneal abrasions, 6 exudative age-related macular degeneration in fellow eye). There were six instances of conversion to exudative age-related macular degeneration found in the other eye at a routine follow-up visit following the injection clinic. CONCLUSION: An injection-only clinic may provide a reasonable approach to streamline retina practices to ensure that patients receive timely injections.

Expression of Vascular Endothelial Growth Factor Receptors in Benign Vascular Lesions of the Orbit: A Case Series.

PURPOSE: Vascular lesions of the orbit, although not malignant, can cause morbidity because of their location near critical structures in the orbit. For the same reason, they can be challenging to remove surgically. Anti-vascular endothelial growth factor (VEGF) drugs are increasingly being used to treat diseases with prominent angiogenesis. Our study aimed to determine to what extent VEGF receptors and their subtypes are expressed on selected vascular lesions of the orbit. DESIGN: Retrospective case series of all orbital vascular lesions removed by one of the authors (JAG) at the Mayo Clinic. PARTICIPANTS: A total of 52 patients who underwent removal of vascular orbital lesions. METHODS: The pathology specimens from the patients were retrieved, their pathologic diagnosis was confirmed, demographic and clinical information were gathered, and sections from vascular tumors were stained with vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor receptor type 1 (VEGFR1), vascular endothelial growth factor receptor type 2 (VEGFR2), and vascular endothelial growth factor receptor type 3 (VEGFR3). MAIN OUTCOME MEASURES: The existence and pattern of staining with VEGF and its subtypes on these lesions. RESULTS: There were 28 specimens of venous malformations, 4 capillary hemangiomas, 7 lymphatic malformations, and 6 lymphaticovenous malformations. All samples stained with VEGF, 55% stained with VEGFR1, 98% stained with VEGFR2, and 96% stained with VEGFR3. Most (94%) of the VEGFR2 staining was diffuse. CONCLUSIONS: Most orbital vascular lesions express VEGF receptors, which may suggest a future target for nonsurgical treatment.

Unilateral Retinal Vasculitis as the Presenting Manifestation of Parry-Romberg Syndrome (Progressive Hemifacial Atrophy).

Purpose: This work aims to present a case of retinal vasculitis associated with Parry-Romberg syndrome. Method: A case report is presented. Results: A 17-year-old man with new floaters was found to have 20/40 vision with 1+ vitreous cell and retinal vasculitis in the right eye only. Workup for infectious etiologies did not reveal an explanation for the retinal vasculitis. However, magnetic resonance imaging of the head showed areas of linear band-like atrophy and scarring of the scalp and soft tissues as well as areas of gliosis and encephalomalacia in the subcortical white matter, all of which were consistent with Parry-Romberg syndrome. The patient was prescribed oral steroids and methotrexate, and the retinal vasculitis improved. Conclusions: Parry-Romberg syndrome is a rarely reported cause of retinal vasculitis and should be kept in the differential for retinal vasculitis.

Risk of cancer in a large cohort of U.S. veterans with diabetes.

Prior studies of cancer risk among diabetic men have reported inconsistent findings. The aim of this study was to assess the risk of cancer among a large cohort (n = 4,501,578) of black and white U.S. veterans admitted to Veterans Affairs hospitals. The cancer risk among men with diabetes (n = 594,815) was compared to the risk among men without diabetes (n = 3,906,763). Poisson regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). Overall, men with diabetes had a significantly lower risk of cancer (RR = 0.93, 95%CI = 0.93-0.94). Men with diabetes, however, had increased risks of cancers of the liver (RR = 1.95, 95%CI = 1.82-2.09), pancreas (RR = 1.50, 95%CI = 1.42-1.59), biliary tract (RR = 1.41, 95%CI = 1.22-1.62), colon (RR = 1.20, 95%CI = 1.16-1.25), rectum (RR = 1.12, 95%CI = 1.07-1.18), and kidney (RR = 1.09, 95%CI = 1.03-1.16), as well as leukemia (RR = 1.14, 95%CI = 1.08-1.21) and melanoma (RR = 1.13, 95%CI = 1.03-1.24). In contrast, men with diabetes had decreased risks of cancers of the prostate (RR = 0.89, 95%CI = 0.87-0.91), brain (RR = 0.91, 95% CI = 0.82-0.99), buccal cavity (RR = 0.85, 95%CI = 0.82-0.89), lung (RR = 0.79, 95%CI = 0.77-0.80), esophagus (RR = 0.77, 95%CI = 0.72-0.82), and larynx (RR = 0.76, 95%CI = 0.71-0.80). These findings indicate that black and white men with diabetes are at significantly lower risk of total cancer and of two of the most common cancers among U.S. males; lung and prostate cancers. These decreased risks were offset, however, by increased risks of cancer at several sites. Hyperinsulinemia may explain the increased risks of the digestive cancers, while lower testosterone levels, in the case of prostate cancer, and higher BMI, in the case of lung cancer, may explain the decreased risks of those tumors.

Accounting for model uncertainty in estimating global burden of disease.

OBJECTIVE: To illustrate the effects of failing to account for model uncertainty when modelling is used to estimate the global burden of disease, with specific application to childhood deaths from rotavirus infection. METHODS: To estimate the global burden of rotavirus infection, different random-effects meta-analysis and meta-regression models were constructed by varying the stratification criteria and including different combinations of covariates. Bayesian model averaging was used to combine the results across models and to provide a measure of uncertainty that reflects the choice of model and the sampling variability. FINDINGS: In the models examined, the estimated number of child deaths from rotavirus infection varied between 492,000 and 664,000. While averaging over the different models' estimates resulted in a modest increase in the estimated number of deaths (541,000 as compared with the World Health Organization's estimate of 527,000), the width of the 95% confidence interval increased from 105,000 to 198,000 deaths when model uncertainty was taken into account. CONCLUSION: Sampling variability explains only a portion of the overall uncertainty in a modelled estimate. The uncertainty owing to both the sampling variability and the choice of model(s) should be given when disease burden results are presented. Failure to properly account for uncertainty in disease burden estimates may lead to inappropriate uses of the estimates and inaccurate prioritization of global health needs.

LOCALIZATION OF MACULAR CRYSTALS ASSOCIATED WITH CHRONIC RETINAL DETACHMENT TO THE POSTERIOR HYALOID USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To present a case of crystalline retinopathy associated with chronic retinal detachment and localize the macular crystals using spectral domain optical coherence tomography. METHODS: Case Report. RESULTS: A 37-year-old man with previously treated chronic retinal detachment presented with normal vision and crystalline maculopathy. Spectral domain optical coherence tomography localized the macular crystals to the posterior hyaloid membrane and on the internal limiting membrane, but not within the retina. CONCLUSION: The macular crystals in crystalline retinopathy associated with chronic retinal detachment most likely originate in the subretinal space beneath the detached retina, migrate through the retinal break into the vitreous cavity, and lodge on the surface of the internal limiting membrane. When the posterior hyaloid membrane separates, the crystals, which are attached to the posterior hyaloid membrane, elevate from the retina.

Intraocular Pressure after Intravitreal Triesence Injection.

PURPOSE: Elevated intraocular pressure (IOP) is a frequent adverse event associated with intravitreal triamcinolone acetate injection. The incidence of elevated IOP with preserved forms of triamcinolone has been studied but the effect of preservative-free formulations has not been clinically evaluated. DESIGN: A retrospective, observational clinical study. METHODS: For patients undergoing intravitreal injections over the study period, age, sex, history of glaucoma or ocular hypertension were recorded. For each injection, preinjection IOP, maximum IOP (IOPmax), dose, and indication for injection were noted for both eyes. RESULTS: Fourteen patients received 72 injections in 18 eyes. The mean baseline IOP was 15.4 mm Hg; the mean IOPmax was 19.8 mm Hg (P<0.001), occurring 63 days after injection. Outcomes were not significantly different between patients receiving 2 or 4 mg doses. History of glaucoma did not significantly affect IOPmax. CONCLUSIONS: Eyes should be monitored for IOP rises after preservative-free triamcinolone acetonide injections.

Intakes of plain water, moisture in foods and beverages, and total water in the adult US population--nutritional, meal pattern, and body weight correlates: National Health and Nutrition Examination Surveys 1999-2006.

BACKGROUND: There is a surprising paucity of studies that have systematically examined the correlates of water intake in the US population. OBJECTIVE: The objective was to examine the association of contributors of water intake with dietary characteristics, meal consumption, and body weight in the US population. DESIGN: We used 24-h dietary recall data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 (n = 12,283) and the NHANES 2005-2006 (n = 4112) to examine the independent association of intakes of plain water, beverage moisture, food moisture, and total water with sociodemographic factors, dietary characteristics (energy, nutrients, diet quality, and energy density), and meal patterns (number of eating episodes, mention of breakfast or snack) by using multiple regression methods. RESULTS: In 2005-2006, American adults reported consuming 3.18 L of total water within the previous 24 h (in 1999-2004, estimated total water intake was 3.35 L), with plain water and beverages contributing 33% and 48% of the total, respectively. Plain water intake was unrelated to the intake of energy and body mass index but was positively related to dietary fiber and inversely related to beverages, sugars, and the energy density of foods; these associations were in the opposite direction for beverage moisture intake. Total water intake was inversely related to energy from fat and energy density but positively related to dietary fiber, caffeine, alcohol, and diet quality. The number of eating episodes predicted higher beverage and food moisture and total water intakes. A higher body mass index predicted higher intakes of beverage moisture and total water. CONCLUSION: Various contributors of total water intake differed in their association with dietary characteristics and body weight in the adult US population.