Ocular side effects of target therapy and immunotherapy in patients with cutaneous malignant melanoma.

PURPOSE: To examine the nature and frequency of ocular side effects due to systemic target therapy with BRAF and MEK inhibitors as well as immunotherapy with cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) monoclonal antibodies used in the treatment of cutaneous malignant melanoma (CMM). DESIGN: While proven effective in cancer treatment, target therapy and immunotherapy have been associated with ocular side effects likely due to their ability to alter the immune privilege of the eye. We conducted a retrospective chart review of patients undergoing target and immunotherapy for CMM and documented all associated eye findings. METHODS: We reviewed the records of 34 patients receiving target and immunotherapy for CMM who were examined in the academic ophthalmology clinic between 2012 and 2017. RESULTS: Ocular side effects were present in 41.1% of patients in this study with 14.7% presenting with uveitis. Patients undergoing therapy with either vemurafenib only or dabrafenib/trametinib combination therapies comprised 70.5% of the study cohort. Ocular side effects occurred in 45.5% and 46.1% of patients on vemurafenib and dabrafenib/trametinib combination therapy, respectively. About 47.5% of males presented with ocular side effects compared to 30.5% of females. Notably, 13/14 patients with ocular symptoms recovered. CONCLUSION: This study highlights the frequency of ocular side effects in patients treated with target therapy and immunotherapy for CMM and shows that symptom resolution can be effectively achieved with proper ophthalmic care. Further research is required to answer whether cessation of these therapies is mandatory during ophthalmic treatment.

Risk Factors for Open-angle Glaucoma in Persons of Latin American Descent.

PURPOSE: The aim of this paper is to concisely summarize what is currently known about OAG among persons of LAD in the United States for the purpose of improving individualized care and highlighting areas requiring further study. MATERIALS AND METHODS: Review of relevant literature was performed through PubMed and Google Scholar from October 1978 through November 11, 2019. RESULTS: As the Latin American population grows within the United States, it is predicted that by 2050, men of LAD will make up the largest demographic group with OAG. Persons of LAD experience a greater increase in OAG prevalence per decade of life compared with persons of African descent and may have unique risk factors. In particular, those with African ancestry and hypertension are at greater risk of elevated intraocular pressure (IOP). Maximum IOP, variability in IOP, and diabetes are also important considerations. Unique anatomic and physiological characteristics such as scleral tensile strain, longer axial length, thin corneas, and corneal hysteresis may play a role in this population's unique risk for the development and progression of OAG. CONCLUSIONS: OAG represents a growing concern among persons of LAD in the United States; however, information on specific risk factors in this population currently remains limited. Studies should be designed to investigate the LAD population and their respective structural, vascular, and social risk factors for the development and progression of OAG to assist clinicians in improving outcomes for this growing population.

Review of non-invasive intracranial pressure measurement techniques for ophthalmology applications.

Assessment and monitoring of intracranial pressure (ICP) are important in the management of traumatic brain injury and other cerebral pathologies. In the eye, ICP elevation and depression both correlate with optic neuropathies, the former because of papilledema and the latter related to glaucoma. While the relationship between ICP elevation and papilledema is well established, the relationship between low ICP and glaucoma is still poorly understood. So far, ICP monitoring is performed invasively, but this entails risks including infection, spurring the study of non-invasive alternatives. We review 11 methods of non-invasive estimation of ICP including correlation to optic nerve sheath diameter, intraocular pressure, ophthalmodynamometry and two-depth transcranial Doppler of the ophthalmic artery. While none of these methods can fully replace invasive techniques, certain measures show great potential for specific applications. Although only used in small studies to date, a MRI based method known as MR-ICP, appears to be the best non-invasive technique for estimating ICP, with two-depth transcranial ultrasound and ophthalmodynamometry showing potential as well.

Differences in Ocular Blood Flow Between People of African and European Descent With Healthy Eyes.

PURPOSE: To investigate differences in ocular blood flow between people of African descent (AD) and European descent (ED) with healthy eyes. MATERIALS AND METHODS: Retrobulbar and retinal capillary blood flow was assessed in 1 eye of 58 participants (24 AD, 34 ED) with healthy eyes with systemic blood pressure lower than 140/90. Retrobulbar blood flow was measured in the ophthalmic artery (OA), central retinal artery (CRA), nasal posterior ciliary artery (NPCA) and temporal posterior ciliary artery (TPCA). Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) were assessed. Retinal capillary blood flow was assessed using mean retinal flow and avascular space defined as the percent of area measured with no blood flow. Groups were compared using t tests and Pearson correlations were compared using Fisher r-to-z transformation. RESULTS: Compared with people of ED, people of AD had significantly lower EDV in the NPCA (P=0.01), and higher RI in the CRA (P=0.04) and TPCA (P=0.01). No significant differences were observed in mean retinal capillary flow or avascular area. In the CRA, a significant negative correlation was observed between pattern standard deviation and peak systolic velocity (P=0.02) in the AD group and this correlation was significantly different from that observed in the ED group (P=0.01). A significant correlation was also observed between pattern standard deviation and EDV (0.04) in the AD group. CONCLUSIONS: This study suggests that retrobulbar blood flow is lower in healthy eyes in persons of AD compared with ED. This may provide a mechanism through which people of AD are at increased risk for ophthalmic diseases such as glaucoma.

Outpatient treatment of periocular infantile hemangiomas with oral propranolol.

BACKGROUND: Propranolol has recently been reported to be useful in the treatment of infantile hemangiomas. However, there are still many questions regarding the dosage, duration, and method of delivery. METHODS: In this retrospective, observational case series, all patients had complete eye examinations and were found to have vision-threatening hemangiomas. All patients had a baseline electrocardiogram. Outpatient, oral propranolol therapy was initiated between 3 weeks and 12 months of age. The dosage was slowly increased to 2 mg/kg daily over the course of 1-2 weeks. Response to therapy was deemed "excellent" (>50% reduction in size), "good" (decreased size but <50%), "fair" (no further growth), or "poor" (continued growth or intolerable adverse effects). RESULTS: A total of 17 patients were treated with oral therapy. Of these, 10 had excellent results, 6 had a good response, 1 fair, and none poor. Mild adverse effects were noted in 6 of the 17 patients and included the following: increased gastric reflux lasting 1 week, intermittent fatigue during the first 2 weeks, gastrointestinal upset, and slight "shakiness" with a missed dose. No symptoms were severe enough to discontinue treatment. All families were satisfied with the treatment. CONCLUSIONS: Outpatient propranolol treatment reduced the size or stopped the growth of all hemangiomas treated, with excellent response in more than half of all patients treated and only minor side effects. Although this is a small initial series, we are encouraged with the efficacy of this treatment modality in comparison with other currently available treatment options.

Nitrogen turnover in the leaf litter and fine roots of sugar maple.

In order to better understand the nitrogen (N) cycle, a pulse of 15NO3- was applied in 1998 to a sugar maple (Acer saccharum) dominated northern hardwood forest receiving long-term (1994-2008) simulated atmospheric N deposition. Sugar maple leaf litter and live fine-root 15N were quantified for four years prior to labeling and for 11 subsequent years. Continuous sampling of 15N following addition of the tracer enabled calculation of leaf litter and fine-root N pool turnover utilizing an exponential decay function. Fine-root 15N recovery peaked at 3.7% +/- 1.7% the year the tracer was applied, while leaf litter 15N recovery peaked in the two years following tracer application at approximately 8%. These results suggest shoots are primarily constructed from N taken up in previous years, while fine roots are constructed from new N. The residence time of N was 6.5 years in leaf litter and 3.1 years in fine roots. The longer residence time and higher recovery rate are evidence that leaves were a stronger sink for labeled N than fine roots, but the relatively short residence time of tracer N in both pools suggests that there is not tight intra-ecosystem cycling of N in this mature forest.