Paul G. Arrigg

Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal Disorders

BACKGROUND Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia. METHODS We measured the concentration of VEGF in 210 specimens of ocular fluid obtained from 164 patients undergoing intraocular surgery, using both radioimmuno-assays and radioreceptor assays. Vitreous proliferative potential was measured with in vitro assays of the growth of retinal endothelial cells and with VEGF-neutralizing antibody. RESULTS VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabetic retinopathy, 29 of 38 samples from patients with neovascularization of the iris, and 3 of 4 samples from patients with ischemic occlusion of the central retinal vein, as compared with 2 of 31 samples from patients with no neovascular disorders (P < 0.001, P < 0.001, and P = 0.006, respectively). The mean (+/- SD) VEGF concentration in 70 samples of ocular fluid from patients with active proliferative diabetic retinopathy (3.6 +/- 6.3 ng per milliliter) was higher than that in 25 samples from patients with nonproliferative diabetic retinopathy (0.1 +/- 0.1 ng per milliliter, P = 0.008), 41 samples from patients with quiescent proliferative diabetic retinopathy (0.2 +/- 0.6 ng per milliliter, P < 0.001), or 31 samples from nondiabetic patients (0.1 +/- 0.2 ng per milliliter, P = 0.003). Concentrations of VEGF in vitreous fluid (8.8 +/- 9.9 ng per milliliter) were higher than those in aqueous fluid (5.6 +/- 8.6 ng per milliliter, P = 0.033) in all 10 pairs of samples obtained simultaneously from the same patient; VEGF concentrations in vitreous fluid declined after successful laser photocoagulation. VEGF stimulated the growth of retinal endothelial cells in vitro, as did vitreous fluid containing measurable VEGF. Stimulation was inhibited by VEGF-neutralizing antibodies. CONCLUSIONS Our data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.

Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation

Excessive retinal vascular permeability contributes to the pathogenesis of proliferative diabetic retinopathy and diabetic macular edema, leading causes of vision loss in working-age adults. Using mass spectroscopy–based proteomics, we detected 117 proteins in human vitreous and elevated levels of extracellular carbonic anhydrase-I (CA-I) in vitreous from individuals with diabetic retinopathy, suggesting that retinal hemorrhage and erythrocyte lysis contribute to the diabetic vitreous proteome. Intravitreous injection of CA-I in rats increased retinal vessel leakage and caused intraretinal edema. CA-I–induced alkalinization of vitreous increased kallikrein activity and its generation of factor XIIa, revealing a new pathway for contact system activation. CA-I–induced retinal edema was decreased by complement 1 inhibitor, neutralizing antibody to prekallikrein and bradykinin receptor antagonism. Subdural infusion of CA-I in rats induced cerebral vascular permeability, suggesting that extracellular CA-I could have broad relevance to neurovascular edema. Inhibition of extracellular CA-I and kallikrein-mediated innate inflammation could provide new therapeutic opportunities for the treatment of hemorrhage-induced retinal and cerebral edema.

Factors associated with visual acuity outcomes after vitrectomy for diabetic macular edema: diabetic retinopathy clinical research network.

Purpose: To evaluate factors ¶associated with favorable outcomes after vitrectomy for diabetic macular edema. Methods: Data were collected prospectively on 241 eyes undergoing vitrectomy for diabetic macular edema. Multivariate models were used to evaluate associations of 20 preoperative and intraoperative factors with 6-month outcomes of visual acuity and retinal thickness. Results: Median central subfield thickness decreased from 412 μm to 278 μm at 6 months, but median visual acuity remained unchanged (20/80, Snellen equivalent). Greater visual acuity improvement occurred in eyes with worse baseline acuity (P < 0.001) and in eyes in which an epiretinal membrane was removed (P = 0.006). Greater reduction in central subfield thickness occurred with worse baseline visual acuity (P < 0.001), greater preoperative retinal thickness (P = 0.001), removal of internal limiting membrane (P = 0.003), and optical coherence tomography evidence of vitreoretinal abnormalities (P = 0.006). No associations with clinicians preoperative assessments of the posterior vitreous were identified. Conclusion: These results suggest that the removal of epiretinal membranes may favorably affect visual outcome after vitrectomy. Preoperative presence of vitreoretinal abnormalities appeared to be associated with somewhat greater reductions in retinal thickness but not with visual acuity outcome. These results may be useful for future studies evaluating vitrectomy for diabetic macular edema.

Computed tomography in the diagnosis of retinoblastoma.

The role of orbital computed tomography (CT) in the management of retinoblastoma is reviewed. All 21 patients with retinoblastoma studied with high-resolution computed tomography had intraocular calcification demonstrable in at least one eye. 83% of tumours showed evidence of calcification on CT scan. The degree of calcification appeared to depend on tumour size; only small tumours were devoid of calcification. The amount and distribution of calcification was similar on both histological study and CT scan. In patients under 3 years old in whom a retinoblastoma is suspected the presence of calcification on CT is virtually diagnostic of it. Patients with leucocoria without calcification on CT probably have a simulating lesion.

Computerized Tomography in the Management of Acute Orbital Cellulitis

The usefulness of computerized tomography (CT scanning) in managing orbital cellulitis is analyzed in six cases. What appears as orbital abscess on CT scan may not be confirmed at surgery. Careful clinical evaluation and responsiveness to antibiotic therapy are most important in determining the need for surgical intervention.

Visual outcomes from pars plana vitrectomy versus combined pars plana vitrectomy, phacoemulsification, and intraocular lens implantation in patients with diabetes.

Purpose: To compare visual acuity outcomes and diabetic retinopathy progression after pars plana vitrectomy (PPV) versus combined pars plana vitrectomy and phacoemulsification (PPVCE) in patients with diabetes. Methods: Retrospective review of 222 consecutive diabetic patients undergoing PPV or PPVCE. Results: A total of 251 eyes of 222 patients were evaluated (PPV = 122, PPVCE = 129). Four-year follow-up was 64% (161 eyes). Overall, patients undergoing PPVCE had better preoperative visual acuity (PPVCE = 20/80, PPV = 20/160, P = 0.03). At 4-year follow-up, visual acuity improved (PPV = +22, PPVCE = +11 letters) compared with baseline in both groups. After correcting for baseline differences in visual acuity, no statistically significant difference in final visual acuity was observed (PPVCE = 20/32, PPV = 20/50, P = 0.09). Results did not differ substantially by surgical indication (vitreous hemorrhage, traction retinal detachment, epiretinal membrane, and/or diabetic macular edema). Cataract progression occurred in 64%, and cataract surgery was performed in 39% of phakic eyes undergoing PPV. Rates of diabetic retinopathy progression, vitreous hemorrhage, and retinal detachment were not statistically different. Neovascular glaucoma developed in 2 patients (2%) after PPV and 6 patients (8%) after PPVCE (P = 0.07). Conclusion: In diabetic patients, equivalent visual acuity improvement over 4 years was observed after PPV or PPVCE. Visual outcomes and retinopathy progression rates were not significantly different after either intervention, suggesting that PPVCE may be appropriate when indicated in patients with diabetes.

Laser Photocoagulation of the Macula

During the past few years, several major clinical trials have been conducted to evaluate the efficacy of laser photocoagulation in the treatment of various macular diseases. There exists a wealth of outstanding literature published by the Macular Photocoagulation Study, Early Treatment Diabetic Retinopathy Study, and Branch Retinal Vein Occlusion Study groups. The conclusions of these studies have revolutionized the management of macular diseases. This book concentrates primarily on the most common retinal disorders, including age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion. In addition, succinct coverage is devoted to the less common macular diseases. This book is divided into concise chapters that review the key clinical findings of each disease. The quality of the fluorescein angiograms is excellent, and they are representative of the pathologic processes described. The major strength of this book is its excellent review of the current management of each macular disorder. The indications for treatment

Familial central serous choroidopathy.

R.Y. Kim (✉ ) Zeiss Humphrey Systems, 5160 Hacienda Drive, Dublin, CA 94568 USA e-mail: robert_kim@humphrey.com Tel: +1–925–5574699, Fax: +1–925–5574775 Fundus fluorescein angiography revealed bilateral window defects, corresponding to the areas of mottled RPE atrophy, and punctate spots of late hyperfluorescence (Fig. 1). The small RPE detachment in the left eye became hyperfluorescent in a sharply demarcated manner. A flash electroretinogram and electro-oculogram were normal. The patient’s healthy 28-year-old daughter worked as a business executive in a „stressful“ environment. A year earlier, she had noticed distortion and blurred vision in the right eye, with best-corrected visual acuities of 20/40 in the right eye and 20/25 in the left (refractive error not recorded). In the right macula was a serous retinal detachment with subretinal yellow dots. The left macula was normal. Fundus fluorescein angiography demonstrated, in the right eye, several areas of window defect and a focal leak two disc diameters temporal to the foveal center; the left eye was normal. Persistence of the symptomatic serous detachment for 10 months led to treatment of the focal leak with laser, leading to resolution.

Postoperative Complications of Pars Plana Vitrectomy for Diabetic Retinal Disease

ABSTRACT Despite recent advances in the medical management of diabetic retinal disease, there remain established indications for vitreoretinal surgery in the treatment of severe proliferative diabetic retinopathy. These include non-clearing vitreous hemorrhage and tractional retinal detachment. Advances in surgical instrumentation, technique, and experience have led to improved visual outcomes, as well as a corresponding decrease in the incidence of postoperative complications. However, the presence of systemic and ocular factors in diabetic patients increases the risk of adverse events compared to non-diabetic individuals. This review will focus on the most important postoperative complications following pars plana vitrectomy, with specific considerations for the diabetic patient.