Importance Glaucoma is a worldwide leading cause of irreversible vision loss. Because it may be asymptomatic until a relatively late stage, diagnosis is frequently delayed. A general understanding of the disease pathophysiology, diagnosis, and treatment may assist primary care physicians in referring high-risk patients for comprehensive ophthalmologic examination and in more actively participating in the care of patients affected by this condition. Objective To describe current evidence regarding the pathophysiology and treatment of open-angle glaucoma and angle-closure glaucoma. Evidence Review A literature search was conducted using MEDLINE, the Cochrane Library, and manuscript references for studies published in English between January 2000 and September 2013 on the topics open-angle glaucoma and angle-closure glaucoma. From the 4334 abstracts screened, 210 articles were selected that contained information on pathophysiology and treatment with relevance to primary care physicians. Findings The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to the level of intraocular pressure, but other factors may also play a role. Reduction of intraocular pressure is the only proven method to treat the disease. Although treatment is usually initiated with ocular hypotensive drops, laser trabeculoplasty and surgery may also be used to slow disease progression. Conclusions and Relevance Primary care physicians can play an important role in the diagnosis of glaucoma by referring patients with positive family history or with suspicious optic nerve head findings for complete ophthalmologic examination. They can improve treatment outcomes by reinforcing the importance of medication adherence and persistence and by recognizing adverse reactions from glaucoma medications and surgeries.

https://jamanetwork.com/journals/jama/articlepdf/1869215/jrv140004.pdf

The Pathophysiology and Treatment of Glaucoma: A Review

The impact of ocular blood flow in glaucoma.

https://www.soard.org/article/S1550-7289(08)00163-9/pdf

ASMBS Allied Health Nutritional Guidelines for the Surgical Weight Loss Patient

Deficiencies in vitamins and other nutrients are common following the Roux-en-Y gastric bypass (RYGBP), biliopancreatic diversion (BPD) and biliopancreatic diversion with duodenal switch (BPDDS), and may become clinically significant if not recognized and treated with supplementation. This paper presents a review of the current literature and evidence of the most commonly deficient vitamins and minerals following weight loss surgery, including protein, iron, vitamin B12, folate, calcium, the fat-soluble vitamins (A, D, E, K), and other micronutrients. The deficiencies appear to be more substantial following malabsorptive procedures such as BPD, but occur with restrictive procedures as well. The review suggests that further studies are needed to evaluate the clinical significance of the nutritional deficiencies, and to determine guidelines for supplementation.

/pdf/nutritional-deficiencies-following-bariatric-surgery-what-29wycer3ei.pdf

Nutritional deficiencies following bariatric surgery: what have we learned?

Prodrugs are molecules with little or no pharmacological activity that are converted to the active parent drug in vivo by enzymatic or chemical reactions or by a combination of the two. Prodrugs have evolved from being serendipitously discovered or used as a salvage effort to being intentionally designed. Such efforts can avoid drug development challenges that limit formulation options or result in unacceptable biopharmaceutical or pharmacokinetic performance, or poor targeting. In the past 10 years, the US Food and Drug Administration has approved at least 30 prodrugs, which accounts for more than 12% of all approved small-molecule new chemical entities. In this Review, we highlight prodrug design strategies for improved formulation and pharmacokinetic and targeting properties, with a focus on the most recently marketed prodrugs. We also discuss preclinical and clinical challenges and considerations in prodrug design and development.

The expanding role of prodrugs in contemporary drug design and development

Aims To explore the gap between diagnostic research outputs and clinical use of optical coherence tomography (OCT) in glaucoma and assess the reliability of a specific reference database when applied to a morphological imaging parameter for diagnostic purposes. Methods Consecutive subjects enrolled in the Multicenter Italian Glaucoma Imaging Study (MIGIS) have been included in this cross-sectional, comparative evaluation of diagnostic tests study. Patients underwent measurement of global and sectorial peripapillary retinal nerve fibre thickness (pRNFL) and minimum rim width (MRW) by OCT. The sensitivity and specificity of reference-database categorical classifications were calculated by means of 2×2 tables and sensitivity was compared with that of the corresponding continuous parameter extracted from the receiver operating characteristic (ROC) curves by matching the specificity. Results 280 Caucasian subjects have been included. At matched specificities, the sensitivity of pRNFL categorical classifications was statistically similar to that of the corresponding continuous parameters, whereas the sensitivity of the MRW categorical classifications was significantly lower than that of the corresponding continuous parameters. Conclusions The diagnostic accuracy of reference database classifications might be lower than that extrapolated from the ROC curves of continuous parameters used in diagnostic research. The gap between the accuracy of these two approaches may be used to estimate the reliability of a specific reference database when applied to a continuous parameter for diagnostic purposes.

https://bjo.bmj.com/content/bjophthalmol/104/8/1114.full.pdf

Exploring the gap between diagnostic research outputs and clinical use of OCT for diagnosing glaucoma

Precis Central corneal thickness (CCT) may increase over time in children affected by primary congenital glaucoma and treated with latanoprost for at least 30 months. Purpose The purpose of this study was to investigate CCT modification over time in a population of primary pediatric glaucoma (PPG) patients prescribed a monotherapy of latanoprost. Materials and methods The present paper reports the results of a post hoc analysis on patients enrolled in the Glaucoma Italian Pediatric Study (GIPSy). Children affected by PPG, with a postsurgical intraocular pressure between 22 and 26 mm Hg and treated with latanoprost monotherapy for at least 30 months were eligible for the analysis. CCT variation from baseline was investigated over the follow-up using univariable and multivariable longitudinal linear mixed models. The impact of age, sex, and intraocular pressure on CCT variation were evaluated taking into account the interaction of each variable with time. Results Twenty-seven eyes (20 patients) were included in the analysis. Mean duration of latanoprost treatment was 36.6 months (SD 2.5) and mean CCT at baseline was 551 μm (SD 37.7). A significant increase of CCT over time was revealed by multivariable analysis, taking into account the impact of age at baseline and its interaction with time (P=0.03). The interaction between age and time was significant (P=0.04), indicating that older age at baseline was associated with lower increase of CCT over time. No variation of CCT was found in univariable analysis (P=0.28). Conclusion In this population of PPG patients treated with latanoprost for at least 30 months, CCT significantly increased over time, when the impact of age and its interaction with time were considered.

The Glaucoma Italian Pediatric Study (GIPSy): The Long-term Effect of Topical Latanoprost on Central Corneal Thickness.

Evaluation of central corneal thickness in patients affected by ocular hypertension, primary open-angle glaucoma, normal tension glaucoma.

Incidence of disc hemorrhage in glaucoma.

Purpose: To compare the number of hyper-reflective retinal spots (HRS) in optical coherence tomography (OCT) images of healthy controls and patients affected with primary open angle glaucoma (POAG). Methods: Thirty patients affected with POAG and 34 healthy controls were recruited and underwent raster OCT examination of the macular region. Among the acquired B-scans, the one with the lowest foveal thickness was selected, and a central area of 3000 μm was defined (region of interest, ROI), in order to identify HRS. HRS were defined as small point-like hyper-reflective elements, detectable at the visual inspection of the OCT image. HRS were independently counted by two investigators in the ROI of each OCT scan. Results: Inter-rater agreement for HRS counting was good to excellent (ICC = 0.96, 95% CI: 0.83–0.99). More HRS were found in the OCT images from glaucoma patients, in comparison with healthy controls (average value: 90.5 ± 13.02 and 74.72 ± 11.35, for glaucoma and healthy subjects, respectively; p < 0.01). Significant correlations between the average number of HRS and visual field mean deviation (MD, p = 0.01) and pattern standard deviation (PSD, p < 0.01) were found. Conclusions: OCT images from glaucoma patients showed a higher number of HRS when compared with healthy controls. As HRS have been hypothesized to be a sign of neuroinflammation, these results may support the role of neuroinflammation in glaucoma etiopathogenesis.

Luciano Quaranta

Papers

Exploring the gap between diagnostic research outputs and clinical use of OCT for diagnosing glaucoma

The Glaucoma Italian Pediatric Study (GIPSy): The Long-term Effect of Topical Latanoprost on Central Corneal Thickness.

Evaluation of central corneal thickness in patients affected by ocular hypertension, primary open-angle glaucoma, normal tension glaucoma.

Incidence of disc hemorrhage in glaucoma.

A Comparison of Hyper-Reflective Retinal Spot Counts in Optical Coherence Tomography Images from Glaucomatous and Healthy Eyes.