Retinopathy Eye Research Articles

Early effect of hydroxychloroquine therapy: relationship between cumulative dose and retinal thickness

Background: Hydroxychloroquine (HCQ) is widely used for long-term treatment of autoimmune diseases such as rheumatoid arthritis. However, its long-term use is known to be associated with visual changes due to retinal damage. Retinal damage associated with long-term HCQ therapy is preventable if the drug is discontinued early when the patients are still asymptomatic. In view of contrasting reports from previous studies, we investigated the association of prolonged HCQ therapy with retinal thickness in macular area.Methods: This study included 48 patients on long-term HCQ therapy and 38 healthy controls. All subjects underwent examination for corrected visual acuity, fundus photography, visual fields and SD-OCT for retinal thickness.Results: Visual acuity, visual fields, fundus photography and SD-OCT did not reveal changes consistent with diagnosis of established HCQ retinopathy in any of the subjects from HCQ group. Retinal thickness in central, parafoveal and perifoveal areas did not show significant differences between HCQ and control groups. However, we observed negative correlation between cumulative dose and retinal thickness in the parafoveal (p = 0.003) and perifoveal areas (p = 0.019) but not in the central area.Conclusions: Correlation of cumulative dose with retinal thickness in parafoveal and perifoveal areas and not the central area is in accordance with the late appearance of HCQ-induced bull's eye retinopathy. Hence screening of asymptomatic patients using OCT seems to be of great importance for early detection of retinal changes.

Retinal Damage in Chloroquine Maculopathy, Revealed by High Resolution Imaging: A Case Report Utilizing Adaptive Optics Scanning Laser Ophthalmoscopy

A 53-year-old Asian woman was treated with hydroxychloroquine and chloroquine for lupus erythematosus. Within a few years, she noticed circle-shaped shadows in her central vision. Upon examination, the patient's visual acuity was 20 / 25 in both eyes. Humphrey visual field (HVF) testing revealed a central visual defect, and fundoscopy showed a ring-shaped area of parafoveal retinal pigment epithelium depigmentation. Fundus autofluorescence imaging showed a hypofluorescent lesion consistent with bull's eye retinopathy. Adaptive optics scanning laser ophthalmoscope (AO-SLO) revealed patch cone mosaic lesions, in which cones were missing or lost. In addition, the remaining cones consisted of asymmetrical shapes and sizes that varied in brightness. Unlike previous studies employing deformable mirrors for wavefront aberration correction, our AO-SLO approach utilized dual liquid crystal on silicon spatial light modulators. Thus, by using AO-SLO, we were able to create a photographic montage consisting of high quality images. Disrupted cone AO-SLO images were matched with visual field test results and functional deficits were associated with a precise location on the montage, which allowed correlation of histological findings with functional changes determined by HVF. We also investigated whether adaptive optics imaging was more sensitive to anatomical changes compared with spectral-domain optical coherence tomography.

Correlation between decreased choroidal blood flow velocity and the pathogenesis of acute zonal occult outer retinopathy

To evaluate changes of choroidal circulation quantitatively using laser speckle flowgraphy in patients with acute zonal occult outer retinopathy. Retrospective observational case series. Sixteen eyes of 11 acute zonal occult outer retinopathy patients: seven non-treated eyes with good visual acuity and nine systemic corticosteroid-treated eyes with progressive visual acuity loss. Six eyes with thyroid-associated ophthalmopathy receiving systemic corticosteroid therapy served as controls. The mean blur rate, an index of quantitative relative blood flow velocity, in the affected area was measured by laser speckle flowgraphy. The changes of mean blur rate, best-corrected visual acuity and the average threshold at the affected area on Humphrey perimetry during 24-week follow up were analysed. Mean blur rate, best-corrected visual acuity, and the average threshold. In non-treated eyes, the average mean blur rate significantly increased at 24 weeks, with a significant increase of the average threshold. In corticosteroid-treated eyes, the mean blur rates at 1, 4, 12 and 24 weeks were significantly higher than the pretreatment value, with significant improvement of best-corrected visual acuity and the average threshold. The increase in mean blur rate at 4 weeks in corticosteroid-treated acute zonal occult outer retinopathy eyes was significantly higher than that in corticosteroid-treated control eyes. In eyes with acute zonal occult outer retinopathy, the mean blur rate at the affected area significantly increases along with improvement of visual functions. These results suggest that impaired choroidal circulation is involved in the pathogenesis of acute zonal occult outer retinopathy.

Influence of intravitreal avastin on the expression of cell factors in retinal proliferative membrane in proliferative diabetic retinopathy eye

Background A main cause of visual impairment in proliferative diabetic retinopathy (PDR) is vitreous hemorrhage and retinal detachment due to contraction of fibrovascular membrane.To explore the pathogenic mechanism of fibrovascular membrane is a new target for the prevention and management of PDR.Objective This study was to determine the change in expression of vascular endothelial growth factor (VEGF),connective tissue growth factor(CTGF) and pigment epithelium derived factor(PEDF) in the proliferative membranes of patients with PDR after intravitreal injection of avastin,an anti-VEGF agent.Methods This study was approved by the Medical Ethic Committee of Tianjin Medical College,and written informed consent was obtained from each patient before enrollment.A prospective randomized-controlled study was designed.Twenty-six eyes of 24 patients with PDR scheduled for surgery were enrolled from January to June,2008 in Tianjin Medical College Eye Hospital.The patients were randomized into the simple vitrectomy group and avastin injection combined with vitrectomy group,with matched gender,age and disease duration.1.25 mg (0.05 ml) of avastin was intravitreally injected prior to surgery,and vitrectomy was performed 10 days after injection in the avastin injection combined with vitrectomy group,and only vitrectomy was given in the simple vitrectomy group.Preretinal membrane was collected during the surgery.Expression of VEGF,CTGF and PEDF in the preretinal membranes was assayed by immunochemistry.Results VEGF,CTGF and PEDF were expressed in the cytoplasm.The rate of VEGF expression in the preretinal membranes was 30.77％ in the avastin injection combined with vitrectomy group,showing a significant reduction in comparison with the simple vitrectomy group(100.00％)(U =4.000,P＜0.01).The rate of expression CTGF was remarkable elevated in the avastin injection combined with vitrectomy group compared with the simple vitrectomy group (92.31％ vs.62.54％)(U=7.500,P=0.048).However,no significant difference was found in the expression rate of PEDF between the two groups(100.00％ vs.92.31％) (U =65.500,P =0.299).Conclusions The results suggest that intravitreal injection of anti-VEGF drugs resulted in the decrease of VEGF expression and increased CTGF expression in proliferative membranes from patients with PDR. Key words: Anti-vascular endothelial growth factor/avastin; Diabetic retinopathy; Retinal proliferative membrane; Vascular endothelial growth factor; Connective tissue growth factor; Pigment epithelium derived factor

Peripheral Nonperfusion and Tractional Retinal Detachment Associated with Congenital Optic Nerve Anomalies

To report an association of congenital optic nerve anomalies with peripheral retina nonperfusion and to describe the clinical manifestations and treatment. Retrospective, observational case series. Fifteen patients with congenital optic nerve anomalies referred for pediatric retina consultation were studied. Sixteen eyes of 9 patients with optic nerve hypoplasia and 8 eyes of 6 patients with other congenital optic nerve anomalies, including optic nerve coloboma, morning glory disc, and peripapillary staphyloma, were included. All patients underwent examinations under anesthesia. Wide-angle retina photographs and fluorescein angiograms were reviewed. The severity of nonperfusion was graded. The presence of fibrovascular proliferation (FP), vitreous hemorrhage (VH), and tractional retinal detachment (TRD) were documented. Anatomic outcome after treatment was recorded. Severity of nonperfusion, occurrence of secondary complications, and the anatomic outcome of patients who underwent laser treatment. In patients with optic nerve hypoplasia, 12 of 16 eyes (75%) had severe peripheral nonperfusion, 12 of 16 eyes (75%) had FP, 3 of 16 eyes (19%) had VH, and 10 of 16 eyes (63%) had TRD. Six of these eyes with severe nonperfusion received laser photocoagulation to the nonperfused retina; laser-treated retinas remained attached in all 6 eyes. In patients with the other optic nerve anomalies, 7 of 8 eyes (88%) had mild to moderate nonperfusion, 2 of 8 eyes (25%) had FP, 1 of 8 eyes (12%) had VH, and 2 of 8 eyes (25%) had TRD. Six of 9 patients (67%) with optic nerve hypoplasia and 1 of 6 patients (17%) with other anomalies had a coexisting congenital brain disease. Congenital optic nerve anomalies may be associated with peripheral retina nonperfusion and the secondary complications of FP, VH, and TRD. In this select group of patients, the nonperfusion associated with optic nerve hypoplasia seemed to be more severe and associated more frequently with secondary complications. Peripheral retina examination in eyes with optic nerve anomalies may identify nonperfusion or FP. Laser treatment of the avascular retina may have helped prevent complications from proliferative retinopathy in eyes clinically observed to have progressed or considered at risk for progression to proliferative retinopathy.

Spectral imaging technique for retinal perfusion detection using confocal scanning laser ophthalmoscopy

To evaluate retinal perfusion in the human eye, a dual-wavelength confocal scanning laser ophthalmoscope (cSLO) was developed that provides spectral imaging of the fundus using a combination of red (670 nm) and near-infrared (810 nm) wavelengths. The image of the ocular fundus was analyzed to find out if quantitative measurements of the reflectivity of tissue permit assessment of the oxygen perfusion of tissue. We explored problems that affect the reproducibility of patient measurements such as non-uniformity errors on the image. For the first time, an image processing technique was designed and used to minimize the errors of oxygen saturation measurements by illumination correction in retina wide field by increasing SNR. Retinal images were taken from healthy and diabetic retinopathy eyes using the cSLO with a confocal aperture of 100 μm. The ratio image (RI) of red/IR, as oxygen saturation (SO2) index, was calculated for normal eyes. The image correction technique improved the reproducibility of the measurements. Average RI intensity variation of healthy retina tissue was determined within a range of about 5.5%. The capability of the new technique to discriminate oxygenation levels of retinal artery and vein was successfully demonstrated and showed good promise in the diagnosis of the perfused retina.

Development of Digital Image Processing using Fuzzy Gaussian Filter Tool for Diagnosis of Eye Infection

retinopathy eye disease which is harmful, cuases pressure in eye nerve fiber. Therefore it is essential to diagnose it earlier. In this paper we have process on images of retina with the help of Digital Image Processing (DIP) tool. In which images are getting detected and then processed. We distinguish the problem of detecting edges in images as a fuzzy logic problem. The edge detection problem can be separated into three stages: filtering, detection, and tracing. Images separated with the application of fuzzy reasoning based on local pixel characteristics which can control the degree of Gaussian smoothing. Filtered images are then applied to a simple edge detection algorithm which evaluates the edge fuzzy association value for each pixel, based on local image characteristics (1).

Five Year Incidence of Visual Field Loss in Adult Chinese. The Beijing Eye Study.

PurposeTo describe the cumulative 5 year incidence of visual field loss in adult Chinese in Greater Beijing.MethodsThe Beijing Eye Study 2006 included 3251 subjects (mean age 60.4±10.1 years) who had participated in the Beijing Eye Study 2001 and returned for re-examination. All participants underwent a comprehensive eye examination, including visual field test by frequency doubling threshold perimetry. An abnormal visual field was defined as reduced sensitivity in at least one test location. Incident visual field loss was defined as a change in visual field from normal at baseline to abnormal at follow-up.ResultsAn incident visual field loss was detected in 273 eyes (4.3±0.5%) /235 subjects (7.3±0.5%). It was significantly associated with higher age (P = 0.001), higher intraocular pressure (P<0.001), and higher fasting blood glucose concentration (P = 0.019). Considering only eyes (n = 140) with a detected cause for visual field loss, the most frequent causes were cataract (68 (48.6%) eyes) followed by glaucoma (23 (16.4%) eyes), diabetic retinopathy (13 (9.3%) eyes), age-related macular degeneration (10 (7.1%) eyes), and myopic degenerative retinopathy (9 (6.4%) eyes). For 133 (48.7%) eyes with a visual field loss, the cause for the VFL remained unclear.ConclusionsThe 5-year incidence of visual field loss was 4.3±0.5% per eye or 7.3±0.5% per subject. It increased significantly with age, intraocular pressure, and fasting blood glucose level. Major causes for the incidence of visual field loss were cataract, glaucoma and diabetic retinopathy.

Influence of vitrectomy for corneal thickness in diaebetic retinopathy eyes with Pentacam

Background The research of corneal thickness after pars plana vitrectomy in DM patient plays an important role not only theoretically but clinically. Objective Present study was to evaluate the change in corneal thickness after pars plana vitrectomy. Methods A prospective coherent study was designed.Seventy-five eyes of 70 consecutive diabetic retinopathy(DR) patients were collected in Tianjin Medical University Eye Center.Pentacam was used to assess the central and periphery corneal thickness by the same investigator preoperatively and 7 days,1 and 3 months postoperatively,respectively.The thickness values from five corneal zone were obtained,including cornea vertex,the thinnest point of the cornea,periphery cornea near the scleral incision of 4 mm away to vertex of cornea on vertical and 240°,120°,60° meridian ( right eye) or 300°,120°,60° meidian ( left eye ).These results were compared and analyzed with ANOVA of repeated measurement data.Subgroup analysis was performed to evaluate the influence of different corneal positions,the use of conventional 20g or 23g transconjunctival sutureless vitrectomy(TSV) groups,surgery duration,gas or fluid endotamponde on corneal thickness.This study was approved by Ethic Committee of this hospital.Written informed consent was obtained from the subjects before any relative medical procedure. Results The mean corneal thickness was ( 639.9 ± 103.1 ),( 689.5 ± 119.3 ),( 666.5 ±113.7),( 650.8 ± 108.6 ) μm before operation,postperative 7 days,1 and 3 months respectively.As covariates appearing in the model,the corneal thickness change rates were revised as the parameters as following: diabeitc duration =13.0 and age =57.2.The revised corneal thickness was significant different among various time points( F=210.928,P=0.000) and different corneal zones(F=24.843,P=0.000) with the size order in turn P4＞P3＞P1＞P2＞P5.The corneal thickness change rates were less in 23g TSV group compared with conventional 20-g group (F =53.843,P =0.000) and BSS tamponade group compared with gas tamponade group ( F =5.288,P =0.022).But no significant difference was found in the revised corneal thickness among surgery duration ＜ 1 hour group,1-2 hour group and ＞2 hour group( F=1.233,P =0.293). Conclusions Vitrectomy is a safe procedure on the ground of cornea,but TSV and fluid endotamponade appear to be more beneficial to the protection of cornea.Pentacam could offer the reliable data in not only central cornea but also periphery cornea. Key words: Corneal thickness/center, periphery; Transconjunctival sutureless vitrectomy; Diabetic retinopathy

Risk of retinal neovascularization in the second eye in patients with proliferative diabetic retinopathy

This study aimed to evaluate the risk of proliferative diabetic retinopathy (DR) in the fellow eye of an eye with existing proliferative DR. Our DR screening programme database listed 1513 diabetes patients alive at the time of the study. Seventy-six had proliferative DR in one or both eyes. In 28 of the 76 (37%) diabetes patients, proliferative DR was diagnosed in both eyes at the same examination. Another 28 patients developed proliferative DR in the second eye within 5 years of its diagnosis in the first eye, bringing the total number of diabetes patients with proliferative DR in both eyes at 5 years to 56 (74%). Almost all the diabetes patients eventually developed proliferative DR in the second eye. The median duration of diabetes before the development of proliferative retinopathy was 19 years for type 1 and 14 years for type 2 diabetes. Proliferative DR is a bilateral disease. Diabetes patients with proliferative DR in one eye are at high risk of developing neovascularization in the second eye and close follow-up is recommended.

Visual acuity of patients of proliferative diabetic retinopathy after vitreoretinal surgery

Objective To observe the visual acuity of different stages of proliferative diabetic retinopathy (PDR) eyes after vitrectomy and analyze the risk factors of blindness. Methods A total of 384 eyes of 300 patients underwent vitrectomy for PDR were followed up. All cases were divided into three groups according to different stage of PDR (stage Ⅳ, stage Ⅴ and stage Ⅵ), the effect of vitrectomy were compared among these groups. Results The final visual acuity increased in 271 eyes (70.6%), among them there were 171 eyes (185.5%) in stage Ⅳ-Ⅴ, and 100 eyes (54.3%) in stage Ⅵ, and there was statistical difference between these two groups (χ~2 = 44.78, P< 0.05). 82. 8% of early-treated and 64.6% of middle/late- treated stage Ⅵ patients had postoperative visual acuity above 0. 05 (χ~2= 4. 861, P<0. 05). 39.5% (131 eyes) of 332 eyes with diabetic blindness was still blind after surgery. Conclusion Visual acuity can be improved in the majority of PDR eyes after vitrectomy, early prevention and early treatment are the keys to avoid diabetic blindness. Key words: Diabetic retinopathy/therapy; Vitrectomy/methods; Vision, binocular

Deficient activation and different expression of transforming growth factor-beta isoforms in active proliferative diabetic retinopathy and neovascular eye disease.

An increased expression and secretion of angiogenic growth factors was proposed to occur in proliferative diabetic retinopathy and other neovascularizing retinal diseases. However, a loss of anti-angiogenic factors also might promote retinal neovascularization. Therefore we investigated the active and latent vitreous levels of the subtypes of the endothelial anti-mitogen transforming growth factor-beta in vitreous of 58 patients. Four groups of patients were compared: Controls without retinal hypoxia, patients with quiescent and active proliferative diabetic retinopathy (PDR), and patients with severe retinal hypoxia resulting in rubeosis iridis. Whereas the amount of total TGF-beta in the four groups did not differ significantly, latent TGF-beta isoform expression showed complex alterations in ocular vitreous. Levels of active TGF-beta of patients with active PDR (79.5 +/- 28 pg/ml; n = 8) were decreased to 20% of the control levels (378 +/- 55 pg/ml; n = 12; p = 0.0005) and 25% of the mean concentration in quiescent PDR (346 +/- 64 pg/ml; n = 9; p = 0.0021). Levels in rubeosis (52 +/- 10 pg/ml; n = 10) did not differ significantly from those found in active PDR but were decreased to 15% of those in patients with quiescent PDR (p = 0.0004). Furthermore a highly significant inverse correlation between active TGF-beta and alpha2-antiplasmin, a liver produced inhibitor of the activation of TGF-beta by plasmin was noted (r = -0.59; n = 28; p = 0.001). We conclude that deficient activation of TGF-beta occurs in active proliferative diabetic retinopathy and in hypoxic angiogenesis most likely as a consequence of a blood retina barrier breakdown and influx of alpha2-antiplasmin from serum. The disinhibition of endothelial cell proliferation may be a central component in the process of neovascularization.

Quantitative fluorescein angiograms

Abstract Purpose: Clinical assessment of quantitative fluorescein angiograms based on novel instrumentation adaptation. Methods: Fluorescein angiograms were simultaneously performed on patient’s retinas and on standard cells composed of two sets of five standard fluorescein solutions mimicking the environmental conditions of the plasma and vitreous, respectively. Regular gray‐scale fluorescein angiograms were converted into absolute concentration image maps, after a deconvolution step for the separation of plasma and vitreous fluorescence contributions, taking into account the respective fluorescein quantum efficiencies. Diabetic retinopathy eyes, eyes before and 3 days after laser photocoagulation, and fellow‐eyes from patients with choroidal neovascularization were imaged using this new technique. Results: Repetitive measurements over patients clearly show the advantage of correcting for instrumentation setup. Comparison of scans taken before and after laser photocoagulation demonstrates background values within the same range and the expected increase over laser spots. Conclusions: Quantitative fluorescein angiograms compare favorably with conventional fluorescein angiograms by removing instrumentation setup bias and by allowing absolute concentration image maps to be built and comparable. Furthermore, the use of a non‐linear color‐coded map allows the detection of subtle differences not visible on regular fluorescein angiograms. It is realized that this first step needs to be complemented by other standardization procedures, e.g., by fundus reflectance.

Spectrum of eye disorders among diabetes mellitus patients in Gaborone, Botswana

This cross-sectional study was designed to determine the spectrum and prevalence of eye disorders among diabetes mellitus (DM) patients in Gaborone, Botswana. All DM patients who attended Gaborone City Council (GCC) health facilities underwent eye examination at the specialist eye clinic. All of the study participants were interviewed using questionnaires and underwent laboratory investigations. A total of 401 DM patients participated in the study. About 60 % never had an eye examination before. Refractive error (29.2%) was the most prevalent followed by cataract (20.2%), retinopathy (9.2%), pterygeum (6.7%), glaucoma (2.5%) and keratopathy (0.7%). The study showed that DM patients are affected by many eye disorders other than diabetic retinopathy and regular eye examination should be part of diabetic care.

Rapid Progression of Diabetic Retinopathy in Eyes With Posterior Uveitis

To report on two patients who developed rapid progression of asymmetric diabetic retinopathy (DRP) in eyes affected by posterior uveitis in contrast to their fellow eyes not affected by uveitis. Observational case report. Two patients with diabetes mellitus (DM) and unilateral uveitis underwent repeated ophthalmologic examinations and fluorescein angiography. Two patients with DM and unilateral posterior uveitis developed proliferative DRP in eyes with previous uveitis within 3 months after the uveitis subsided. In contrast, the retinal findings of nonuveitic eyes remained unchanged on follow-up of several years. Since the pathogenesis of intraocular inflammation and diabetic retinopathy acts through similar biochemical mediators and pathways, it is feasible that posterior uveitis accelerates the progression of diabetic retinopathy. Our results support this hypothesis and point out a risk for rapid retinopathy development in eyes affected with posterior uveitis.

Diabetic papillopathy in type II diabetic patients.

To evaluate the patient characteristics and fundus findings of patients with type II diabetes presenting with diabetic papillopathy. The authors retrospectively reviewed the medical records of 3,235 patients with diabetes followed in their institution since 1986 and identified the patients with unilateral or bilateral transient disk swelling and without significant deterioration of best-corrected visual acuity. The authors investigated patient demographics, symptoms, fundus findings, ancillary test results, and clinical course of those patients. Twenty-four eyes of 16 patients with type II diabetes mellitus met the criteria. Patients had a mean age of 57.1 (+/-8.8) years and had diabetes mellitus of long duration (mean 10.0 +/- 8.6 years). Approximately half of the patients had poor metabolic control. Disk swelling was bilateral in 8 (50%) patients and resolved in an average of 7.8 +/- 3.7 months. A total of 13 (54%) eyes had nonproliferative and 2 (8%) eyes had proliferative diabetic retinopathy at presentation. In 4 (17%) eyes retinopathy progression into the proliferative stage occurred and panretinal photocoagulation was performed. Diabetic papillopathy may be found in older patients with type II diabetes. Nonproliferative or proliferative diabetic retinopathy as well as macular edema may also be associated with this disorder.

Effect of cataract surgery on the progression of diabetic retinopathy

Purpose: To study the effect of cataract surgery and other factors on the progression of diabetic retinopathy using the nonoperated contralateral eye as a control. Setting: Department of Ophthalmology, Catholic University Medical College, Uijongbu St. Mary’s Hospital, Seoul, Korea. Methods: Monocular cataract surgery was performed in 75 patients who had the same degree of retinopathy or no retinopathy in both eyes preoperatively. Patients were assigned to 1 of 2 groups as follows: Group A, progression of retinopathy in the operated eye caused by cataract surgery; Group B, no progression of retinopathy bilaterally, comparable level of progression in both eyes, or more progression of retinopathy in the nonoperated eye than in the operated eye. The differences between the 2 groups in age, duration of and treatment methods for diabetes, renal function, and presence of preoperative macular edema were compared. The 1-year follow-up included evaluation of the progression of retinopathy. Results: Surgery caused the retinopathy to progress in 23 patients (30.6%, Group A); 52 patients (69.4%, Group B) had no progression of retinopathy or a comparable level of retinopathy postoperatively. The operated eye had more progression of retinopathy than the nonoperated contralateral eye ( P < .05). There was no significant difference between the 2 groups in age, diabetes duration, surgical method, or hypertension. Preoperative macular edema and poor renal function significantly affected the progression of diabetic retinopathy after cataract surgery ( P < .05). Conclusions: Diabetic retinopathy progressed after cataract surgery. The presence of preoperative macular edema and poor renal function increased the progression of retinopathy postoperatively.

Effects of Angiogenic Growth Factor Combinations on Retinal Endothelial Cells☆

The aim of this paper was to determine if growth factors, known to be upregulated in proliferative diabetic retinopathy, exerted combined effects on retinal endothelial cells. The authors explored the individual and collective actions of insulin-like growth factor I (IGF-I), vascular endothelial growth factor (VEGF), platelet-derived growth factor-BB (PDGF-BB), fibroblast growth factor-2 (FGF-2) and placenta growth factor (PlGF) on several parameters that reflect the angiogenic potential of endothelial cells. The effect of growth factors on cell migration and survival/proliferation was examined using primary cultures of bovine retinal endothelial cells (BREC). The authors also determined the growth factor action on capillary-like tube formation on a reconstituted basement membrane matrix and on the newly described phenomenon of secondary sprouting, in which endothelial cell colonies spontaneously survive, proliferate, migrate and invade the matrix after the original capillary-like tubes have collapsed. Sprouting cells were positive for von Willebrand factor and could aggregate into larger tubes with lumens. Incubation with VEGF+IGF-I or PlGF+FGF-2 enhanced tube stability by 40–50%, more than each growth factor alone or other combinations (5–20%). The concurrent addition of four growth factors did not improve the response seen with growth factor pairs. Surprisingly, PDGF-BB induced tube collapse. IGF-I and FGF-2 mildly enhanced BREC proliferation/survival (5–15%). However, VEGF+IGF-I or PlGF+FGF-2 increased BREC proliferation/survival by 25% under low serum conditions, whereas combinations of all four growth factors exerted a clearly synergistic effect (250% increase). PDGF-BB or FGF-2 stimulated secondary sprouting and were the only factors capable of exerting this effect alone. Even though VEGF, IGF-I or PlGF were not effective, if administered in pairs, they demonstrated increased responses. PDGF-BB was also able to enhance the effect of FGF-2+IGF-I+VEGF on BREC secondary sprouting, but not of any of them individually. No other growth factor tested was able to significantly improve the action of combinations of three other growth factors. VEGF increased cell migration in a wounded monolayer assay two-fold and PDGF-BB, 2.5 times, but other individual growth factors were ineffective. PlGF+FGF-2 enhanced cell migration more than each factor alone. VEGF+IGF-I+PlGF+FGF-2, however, increased cell migration four-fold. In summary, this study indicates that growth factors, overexpressed in diabetic retinopathy eyes, enhance the angiogenic characteristics of cultured cells (tube formation, proliferation, secondary sprouting and migration). Their effects, however, can be greatly augmented by other growth factors that alone exert little or no action. Therefore, diabetic retinal neovascularization may result from the additive or synergistic action of several growth factors.

Ophthalmic health care in diabetes mellitus: a cross-sectional study in northern Sweden

The purpose of this study was to estimate the prevalence of diabetic retinopathy, visual impairment/blindness and previous surgical eye treatments in patients with older-onset vs. younger-onset diabetes mellitus. A cross-sectional study of patients with diabetes mellitus in the area of Umeå, Sweden (135,000 inhabitants) was performed during 1994-1995, comprising 1,805 diabetic patients. Diabetic patients of younger ages were referred more frequently than older for fundus examination. With age at diagnosis <30 years retinopathy was seen in 68% of the patients; with age at diagnosis 30 years or older retinopathy was seen in 66% of the insulin-treated, 30% of the oral agent-treated and 7% of the diet-treated patients. Retinopathy that had previously been treated or needed treatment was seen in about one-third of the patients in both the younger-onset and the insulin-treated older-onset groups. The corresponding values for the oral agent-treated and diet-treated older-onset diabetic patients were 9.4% and 0.6%, respectively. No older-onset diabetic patient with acceptable glycemic control and with only dietary treatment had received or needed ophthalmic treatment. In the Umeå area, patients with a relatively short duration of diabetes had a lower prevalence of diabetic retinopathy than that found in Wisconsin in 1979-1980. We conclude that demand for ophthalmic care in general is much higher for older-onset diabetic patients because of the greater number of patients with older-onset than younger-onset diabetes. In addition, older-onset patients should be examined regularly for treatable retinopathy. Diet-treated older-onset diabetic patients with acceptable glycemic control need little ophthalmic screening.

Eye abnormalities in the mentally handicapped

In 1987, a survey of eye abnormalities was undertaken of the mentally handicapped patients in Stoke Park Hospital, Bristol. The total population was 367 patients (262 females and 105 males). Of the 367 patients reviewed, 218 were found to have one or more eye anomalies (including the Down's Syndrome group), which shows that more than half the patients suffered from eye disorders (59%). The prevalence of the following anomalies is presented in detail: strabismus, refractive errors and cataracts. Corneal anomalies, nystagmus, retinopathy, glaucoma and other eye pathologies associated with various syndromes are noted. Eye anomalies in 31 patients suffering from Down's syndrome in the sample are recorded. Preventative measures to ameliorate the defects of eyesight, particularly in the aging population, relevance of regular eye examination and medical or surgical treatment of eye disorders are discussed.