Comparison of systemic variables in patients with diabetes mellitus with and without sickle cell trait (SCT).

<p>Comparison of systemic variables in patients with diabetes mellitus with and without sickle cell trait (SCT).</p

Interaction of significant risk factors on association between sickle cell trait versus proliferative diabetic retinopathy and/or diabetic macular edema, based on logistic regression analysis.

<p>Interaction of significant risk factors on association between sickle cell trait versus proliferative diabetic retinopathy and/or diabetic macular edema, based on logistic regression analysis.</p

Association between sickle cell trait and the prevalence of proliferative diabetic retinopathy, its complications and/or diabetic macular edema.

<p>Association between sickle cell trait and the prevalence of proliferative diabetic retinopathy, its complications and/or diabetic macular edema.</p

Ocular status of right eyes of patients with diabetes mellitus with and without sickle cell trait.

<p>Ocular status of right eyes of patients with diabetes mellitus with and without sickle cell trait.</p

Demographics of patients with diabetes mellitus with and without sickle cell trait.

<p>Demographics of patients with diabetes mellitus with and without sickle cell trait.</p

Independent, non-derived stereometric parameters of the optic nerve and nerve fiber layer in HIV+ patients compared to HIV-seronegative controls.

<p>HIV+ = subjects who are human immunodeficiency virus (HIV) positive, HIV- = subjects who are HIV negative controls, CD4 = CD4 cell count, SD = standard deviation, RNFL = retinal nerve fiber layer, mm–millimeter.</p><p>*—statistically significant</p><p>Independent, non-derived stereometric parameters of the optic nerve and nerve fiber layer in HIV+ patients compared to HIV-seronegative controls.</p

Baseline characteristics of the four groups.

<p>Baseline characteristics of the four groups.</p

Variability of HRT3 retinal nerve fiber layer cross sectional area by retinal regions among HIV+ and HIV-seronegative patients.

<p>HRT = Heidelberg retina tomography, HIV+ = subjects who are human immunodeficiency virus (HIV) positive, HIV- = subjects who are HIV negative controls, CD4 = CD4 cell count, SD = standard deviation, RNFL = retinal nerve fiber layer, Sup = superior, Inf = inferior.</p><p>*—statistically significant</p><p>Variability of HRT3 retinal nerve fiber layer cross sectional area by retinal regions among HIV+ and HIV-seronegative patients.</p

A degenerative retinal process in HIV-associated non-infectious retinopathy

HIV retinopathy is the most common non-infectious complication in the eyes of HIV-positive individuals. Oncotic lesions in the retinal nerve fiber layer, referred to as cotton wool spots (CWS), and intraretinal (IR) hemorrhages are frequently observed but are not unique to this pathology. HIV-positive patients have impaired color vision and contrast sensitivity, which worsens with age. Evidence of inner-retinal lesions and damage have been documented ophthalmoscopically, however their long term structural effect has not been investigated. It has been hypothesized that they may be partially responsible for loss of visual function and visual field. In this study we utilized clinical data, retinal imaging and transcriptomics approaches to comprehensively interrogate non-infectious HIV retinopathy. The methods employed encompassed clinical examinations, fundus photography, indirect ophthalmoscopy, Farmsworth-Munsell 100 hue discrimination testing and Illumina BeadChip analyses. Here we show that changes in the outer retina, specifically in the retinal pigment epithelium (RPE) and photoreceptor outer segments (POS) contribute to vision changes in non-infectious HIV retinopathy. We find that in HIV-positive retinae there is an induction of rhodopsin and other transcripts (including PDE6A, PDE6B, PDE6G, CNGA1, CNGB1, CRX, NRL) involved in visual transduction, as well as structural components of the rod photoreceptors (ABCA4 and ROM1). This is consistent with an increased rate of renewal of rod outer segments induced via increased phagocytosis by HIV-infected RPE previously reported in culture. Cone-specific transcripts (OPN1SW, OPN1LW, PDE6C, PDE6H and GRK7) are uniformly downregulated in HIV positive retina, likely due to a partial loss of cone photoreceptors. Active cotton wool spots and intraretinal hemorrhages (IRH) may not affect photoreceptors directly and the interaction of photoreceptors with the aging RPE may be the key to the progressive vision changes in HIV-positive patients

Regression analyses of HIV status (seronegative vs seropositive) and retinal nerve fiber layers thickness with visual acuity, adjusted for gender.

<p>*Applying Generalized Estimating Equations (GEE); BCVA, best corrected visual acuity; RNFL, retinal nerve fiber layer; ETDRS, Early Treatment Diabetic Retinopathy Study; M1, full-contrast module of white letters presented on a black background; M2, 64% contrast module simulating an environment similar to a dimly lit restaurant; M3, 43% contrast module simulating an environment similar to driving at dusk; G1, full-contrast module of black letters presented on a bright background.</p