Diabetic Retinopathy Preferred Practice Pattern

Diabetic retinopathy (DR), a sight-threatening neurovasculopathy, is the leading cause of irreversible blindness in the developed world. DR arises as the result of prolonged hyperglycemia and is characterized by leaky retinal vasculature, retinal ischemia, retinal inflammation, angiogenesis, and neovascularization. The number of DR patients is growing with an increase in the elderly population, and therapeutic approaches are limited, therefore, new therapies to prevent retinal injury and enhance repair are a critical unmet need. Besides vascular endothelial growth factor (VEGF)-induced vascular proliferation, several other mechanisms are important in the pathogenesis of diabetic retinopathy, including vascular inflammation. Thus, combining anti-VEGF therapy with other new therapies targeting these pathophysiological pathways of DR may further optimize treatment outcomes. Technological advancements have allowed for high-throughput proteomic studies examining biofluids such as aqueous humor, vitreous humor, tear, and serum. Many DR biomarkers have been identified, especially proteins involved in retinal inflammatory processes. This review attempts to summarize the proteomic biomarkers of DR-associated retinal inflammation identified over the last several years.

https://www.mdpi.com/1422-0067/20/19/4755/pdf

Proteomic Biomarkers of Retinal Inflammation in Diabetic Retinopathy.

The purpose of this study was to investigate the association between gender and primary open-angle glaucoma (POAG) among African Americans and to assess demographic, systemic, and behavioral factors that may contribute to differences between genders. The Primary Open-Angle African American Glaucoma Genetics (POAAGG) study had a case-control design and included African Americans 35 years and older, recruited from the greater Philadelphia, Pennsylvania. Diagnosis of POAG was based on evidence of both glaucomatous optic nerve damage and characteristic visual field loss. Demographic and behavioral information, history of systemic diseases and anthropometric measurements were obtained at study enrollment. Gender differences in risk of POAG were examined using multivariate logistic regression. A total of 2,290 POAG cases and 2,538 controls were included in the study. The percentage of men among cases was higher than among controls (38.6% vs 30.3%, P<0.001). The subjects' mean age at enrollment was significantly higher for cases compared to controls (70.2±11.3 vs. 61.6±11.8 years, P<0.003). Cases had lower rates of diabetes (40% vs. 46%, P<0.001), higher rates of systemic hypertension (80% vs. 72%, P<0.001), and lower body mass index (BMI) (29.7±6.7 vs. 31.9±7.4, P<0.001) than controls. In the final multivariable model, male gender was significantly associated with POAG risk (OR, 1.64; 95% CI, 1.44-1.87; P<0.001), after adjusting for age, systemic hypertension, diabetes, and BMI. Within the POAAGG study, men were at higher risk of having POAG than women. Pending genetic results from this study will be used to better understand the underlying genetic variations that may account for these differences.

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Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study: gender and risk of POAG in African Americans.

Background/Aims: Diabetic retinopathy (DR) is one of the main causes of blindness in the world. Our previous study showed that transthyretin (TTR) regulates key g

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Transthyretin Exerts Pro-Apoptotic Effects in Human Retinal Microvascular Endothelial Cells Through a GRP78-Dependent Pathway in Diabetic Retinopathy

Purpose To evaluate vitreous humor (VH) protein expression profiles in patients with proliferative diabetic retinopathy (PDR), with and without intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) before vitrectomy. Methods We enrolled consecutive PDR patients who needed pars plana vitrectomy (PPV) with or without IVI or pan-retinal photocoagulation (PRP). Visual acuity, duration, and treatment of diabetes mellitus, ocular treatment history, and fundus examinations were recorded. VH samples were collected without artificial humor infusion. Label-free quantitative proteomics analysis was performed to determine the protein expression profiles of VH samples. Enzyme-linked immunosorbent assays were performed to validate the proteomics results. Results PDR patients who underwent IVI at a mean of 5.8 days (range, 3-8 days) before PPV (IVI group, n = 12) were younger than PDR patients with a history of PRP (PRP group, n = 29) and untreated PDR patients (control group, n = 21). The duration of diabetes mellitus was similar in the three groups. Label-free quantitative proteomics analysis showed that the signal intensities for fibronectin, fibrinogen α chain, fibrinogen β chain, fibrinogen γ chain, VEGF receptor 1 (VEGFR1), and VEGFR2 were significantly greater in the IVI group than in the other two groups. Enzyme-linked immunosorbent assays validated the results for fibronectin and fibrinogens, but found no significant differences in VEGF or VEGFR2 concentrations. VEGFR1 expression was significantly greater in the IVI and PRP groups than in the control group. Conclusions VH fibronectin and fibrinogen concentrations were highest in the IVI patients, which may promote fibrin-fibronectin complexation and fibrosis in eyes with PDR.

Vitreous Fibronectin and Fibrinogen Expression Increased in Eyes With Proliferative Diabetic Retinopathy After Intravitreal Anti-VEGF Therapy.

Intravitreal Bevacizumab for the Treatment of Vitreous Hemorrhage Due to Proliferative Diabetic Retinopathy.

Objective: African Americans have been historically underrepresented in research studies. Our aim was to evaluate factors influencing enrollment in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Design: Patients approached to enroll in the POAAGG study were asked to complete a 15-item survey addressing demographic characteristics, knowledge of genetics and glaucoma, and opinions on human research. Survey responses were compared between subjects who enrolled (Enrollers) and did not enroll (Decliners) in the POAAGG study. Results: Enrollers (N = 190) were 3.7 years younger (P = 0.007) and had similar gender, education, and income level to Decliners (N = 117). Knowledge about genetics and glaucoma was similar between groups. Enrollers were more comfortable providing DNA for research studies (93.1% vs 54.1%; P < 0.001) and more likely to have participated in prior studies (P = 0.003) and consider participating in future studies (P < 0.001). Among Decliners, lack of time was the primary reason given for not enrolling. Conclusion: To increase participation of African Americans in genetic research studies, efforts should be made to raise comfort with DNA donation.

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Factors associated with participation by African Americans in a study of the genetics of glaucoma.

Purpose To describe a case of reactive lymphoid hyperplasia (RLH) of the conjunctiva responding to cyclosporine immunosuppressant monotherapy. Methods A 66-year-old man with a 2-year history of biopsy-proven bilateral RLH presented for dry eye evaluation with chief complaints of burning, stinging, and irritation in both eyes. After slit-lamp examination and positive findings of matrix metalloproteinase 9 in the patient's tear film, he was diagnosed with meibomian gland dysfunction and tear-insufficiency dry eye disease. The patient was subsequently treated with topical cyclosporine (ophthalmic emulsion 0.5 mg/mL two times per day) in both eyes. Results Examination at the 3-month follow-up visit revealed significant reduction of the RLH lesions bilaterally. Conclusions This report represents the first case of benign ocular RLH responsive to topical cyclosporine therapy. We believe that cyclosporine could play a role in treating patients with benign ocular RLH and warrants further investigation to evaluate its full efficacy.

Benign Reactive Lymphoid Hyperplasia of the Conjunctiva Treated With Cyclosporine.

In-situ hybridization provides a convenient and reliable method to detect human papillomavirus (HPV) infection in formalin-fixed paraffin-embedded tissue. Cases of conjunctival papillomas, conjunctival intraepithelial neoplasia (CIN), conjunctival carcinoma in situ (cCIS), and invasive squamous cell carcinoma (SCC), in which low-risk (LR) and/or high-risk (HR) HPV types were evaluated by RNA or DNA in-situ hybridization, were retrospectively identified. LR HPV types were frequently detected in conjunctival papillomas (25/30, 83%), including 17/18 (94%) with RNA probes, compared to 8/12 (75%) with DNA probes. None of the CIN/cCIS or SCC cases were positive for LR HPV by either method. HR HPV was detected by RNA in-situ hybridization in 1/16 (6%) of CIN/cCIS cases and 2/4 (50%) of SCC cases, while DNA in-situ hybridization failed to detect HPV infection in any of the CIN/cCIS lesions. Reactive atypia and dysplasia observed in papillomas was generally associated with the detection of LR HPV types. Collectively, our findings indicate RNA in-situ hybridization may provide a high-sensitivity approach for identifying HPV infection in squamous lesions of the conjunctiva and facilitate the distinction between reactive atypia and true dysplasia. There was no clear association between HPV infection and atopy in papillomas or dysplastic lesions.

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Detection of Human Papillomavirus in Squamous Lesions of the Conjunctiva Using RNA and DNA In-Situ Hybridization

This case report describes a diagnosis of lamellar and sutural cataract in a patient with a history of poorly controlled type 2 diabetes who presented with bilateral visual decline and significant glare and haloes around lights. 

Rupin N. Parikh

Papers

Intravitreal Bevacizumab for the Treatment of Vitreous Hemorrhage Due to Proliferative Diabetic Retinopathy.

Factors associated with participation by African Americans in a study of the genetics of glaucoma.

Benign Reactive Lymphoid Hyperplasia of the Conjunctiva Treated With Cyclosporine.

Detection of Human Papillomavirus in Squamous Lesions of the Conjunctiva Using RNA and DNA In-Situ Hybridization

Congenital Lamellar and Sutural Cataract in a Patient With Type 2 Diabetes.