Outcome of eyes developing retinal detachment during the Early Treatment for Retinopathy of Prematurity Study (ETROP).

OBJECTIVE: To report the structural and visual outcomes of eyes in which retinal detachment developed from retinopathy of prematurity (ROP) in the Early Treatment of Retinopathy of Prematurity (ETROP) Study. Method Infants in the ETROP Study with bilateral high-risk prethreshold ROP had 1 eye randomized to early treatment, with the fellow eye managed conventionally. In infants with asymmetric disease, the eye with high-risk prethreshold ROP was randomized to early treatment or conventional management. When a retinal detachment was detected, observation or vitreoretinal surgery (ie, scleral buckling and/or vitrectomy) was provided at the discretion of the individual investigator. At 9 months corrected age, retinal examinations were performed and visual acuities were assessed by masked testers using grating acuity. RESULTS: The ETROP Study enrolled 401 patients with high-risk prethreshold ROP. Retinal detachments occurred in 89 eyes of 63 patients. Follow-up was available for 78 eyes of 56 patients. The detachments were bilateral in 21 patients (38%) and were classified as stage 4A in 30 eyes, stage 4B in 14 eyes, and stage 5 in 16 eyes. Detachments were not classified in 18 eyes. Twelve eyes of 11 patients were observed and 66 eyes of 52 patients underwent vitreoretinal surgery. Attachment of the macula at 9 months persisted or was achieved in 17 (30%) of 56 eyes after vitrectomy with or without scleral buckle, in 6 (60%) of 10 eyes after scleral buckle only, and in 2 (17%) of 12 eyes followed up without surgery. Favorable visual acuity (> or =1.85 cycles/degree) was found in 13 (17%) of the 78 eyes. All 6 eyes that maintained normal visual acuity (> or =3.70 cycles/degree) had a stage 4A detachment (1 of 6 managed by observation, 3 of 6 by scleral buckle, and 2 of 18 by vitrectomy). Eleven eyes with stage 5 detachment underwent vitreoretinal surgery, resulting in 6 with no light perception, 3 with light perception only, and 2 with detection of only the low vision card. CONCLUSIONS: In the ETROP Study, the outcome of retinal detachment owing to ROP was generally poor. Vitreoretinal surgery for retinal detachment was associated with macular attachment in 16 of 48 eyes. Normal acuity was maintained after surgical repair of stage 4A retinal detachment in 5 (21%) of 24 eyes. Vitreoretinal surgery for stage 5 disease was associated with some structural successes but poor functional outcomes.

Diabetic retinopathy in Mexican Americans and non-Hispanic whites.

Mexican Americans (MAs) have a threefold greater prevalence of non-insulin-dependent diabetes mellitus (NIDDM) than non-Hispanic Whites (NHWs). Because MA diabetic subjects have greater hyperglycemia and an earlier age of onset than NHW diabetic subjects, we postulated that diabetic MAs might also have more severe diabetic retinopathy. Stereoscopic retinal photographs of the seven standard fields of each eye were taken in 257 MAs and 56 NHWs with NIDDM. The photographs were read by the University of Wisconsin Fundus Photographic Reading Center and graded with standardized criteria. The MAs had a nonsignificantly increased risk of retinopathy relative to the NHWs [odds ratio (OR) = 1.71; 95% confidence interval (Cl) = (0.93, 3.17)]. The risk of severe retinopathy (proliferative or preproliferative) relative to background or no retinopathy was significantly greater in MAs than in NHWs [OR = 2.37; 95% Cl = (1.04, 5.39)]. After control by logistic regression for duration of disease, severity of hyperglycemia, age, and systolic blood pressure, MAs still had an increased risk of severe retinopathy relative to NHWs [OR = 3.18; 95% Cl = (1.32, 7.66)]. Severe retinopathy was related to duration of disease, hyperglycemia, and insulin therapy in both ethnic groups. Previously diagnosed MA diabetic subjects also had an increased prevalence of any retinopathy [OR = 2.39; 95% Cl = (1.63, 3.50)] and severe retinopathy [OR = 3.21; 95% Cl = (2.24, 4.59)] relative to previously diagnosed White diabetic subjects (n = 896) from Wisconsin.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of socioeconomic status on hyperglycemia and retinopathy levels in Mexican Americans with NIDDM.

Mexican Americans have a threefold greater prevalence of non-insulin-dependent diabetes mellitus (NIDDM) than non-Hispanic Whites. Moreover, Mexican-American diabetic people have more severe hyperglycemia and diabetic retinopathy than non-Hispanic White diabetic people. Mexican Americans are predominantly of low socioeconomic status (SES), and low-SES Mexican Americans have a higher prevalence of NIDDM than higher-SES Mexican Americans. Therefore, we hypothesized that among diabetic people, low SES would be associated with more severe hyperglycemia and retinopathy. Three hundred forty-three Mexican Americans and 79 non-Hispanic Whites with NIDDM were identified from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Hyperglycemia was assessed as the sum of the fasting, 1-h, and 2-h plasma glucose concentrations during a standard oral glucose tolerance test. Retinopathy was assessed by 7 standard stereoretinal photographs. SES was assessed with three indicators: Duncan's socioeconomic index, education, and income. Contrary to expectations, low SES was not associated with greater levels of hyperglycemia or grades of retinopathy.

Screening for diabetic retinopathy. The wide-angle retinal camera.

OBJECTIVE: To define the test characteristics of four methods of screening for diabetic retinopathy. RESEARCH DESIGN AND METHODS: Four screening methods (an exam by an ophthalmologist through dilated pupils using direct and indirect ophthalmoscopy, an exam by a physician's assistant through dilated pupils using direct ophthalmoscopy, a single 45 degrees retinal photograph without pharmacological dilation, and a set of three dilated 45 degrees retinal photographs) were compared with a reference standard of stereoscopic 30 degrees retinal photographs of seven standard fields read by a central reading center. Sensitivity, specificity, and positive and negative likelihood ratios were calculated after dichotomizing the retinopathy levels into none and mild nonproliferative versus moderate to severe nonproliferative and proliferative. Two sites were used. All patients with diabetes in a VA hospital outpatient clinic between June 1988 and May 1989 were asked to participate. Patients with diabetes identified from a laboratory list of elevated serum glucose values were recruited from a DOD medical center. RESULTS: The subjects (352) had complete exams excluding the exam by the physician's assistant that was added later. The sensitivities, specificities, and positive and negative likelihood ratios are as follows: ophthalmologist 0.33, 0.99, 72, 0.67; photographs without pharmacological dilation 0.61, 0.85, 4.1, 0.46; dilated photographs 0.81, 0.97, 24, 0.19; and physician's assistant 0.14, 0.99, 12, 0.87. CONCLUSIONS: Fundus photographs taken by the 45 degrees camera through pharmacologically dilated pupils and read by trained readers perform as well as ophthalmologists for detecting diabetic retinopathy. Physician extenders can effectively perform the photography with minimal training but would require more training to perform adequate eye exams. In this older population, many patients did not obtain adequate nonpharmacological dilation for use of the 45 degrees camera.

Ocular perfusion pressure and choroidal blood flow in the rabbit.

PURPOSE: To compare choroidal blood pressure versus flow relationships obtained by three different methods of changing the ocular perfusion pressure. METHODS: Experiments were performed in pentobarbital-anesthetized rabbits with occluders on the aorta and inferior vena cava to control mean arterial pressure (MAP). The central ear artery was cannulated to measure MAP. Two 23-gauge needles were inserted through the pars plana into the vitreous: one connected to a saline-filled syringe to vary the ocular volume and the other to a pressure transducer to measure intraocular pressure (IOP). Choroidal perfusion was measured by laser-Doppler flowmetry with the probe in the vitreous over the posterior pole. In group 1 (n = 15), the MAP was varied while holding the IOP at 10, 15, 20, 25 and 30 mm Hg. In group 2 (n = 19), the IOP was increased while holding the MAP at 80, 70, 60, 50, 40, 30 and 20 mm Hg. In group 3 (n = 21), the MAP was varied without controlling the IOP. RESULTS: Group 1 baseline choroidal flows were similar at the five IOPs. When the flow was plotted against MAP, the curves diverged and extrapolated to intersect the pressure axis when the MAP equaled the set IOP. Group 2 baseline flows were similar at MAPs greater than 40 mm Hg. When the flow was plotted against the IOP, the curves diverged and intersected the pressure axis when the IOP equaled the MAP. In both groups, plotting the flow against the perfusion pressure (i.e., MAP minus IOP) collapsed the data points into single curves. Choroidal autoregulation occurred in all three groups; however, the low end of the autoregulatory perfusion pressure range was approximately 50 mm Hg in group 1, approximately 40 mm Hg in group 2, and approximately 30 mm Hg in group 3. CONCLUSIONS: The results show that the effective choroidal perfusion pressure gradient equals the MAP minus the IOP, and that choroidal autoregulation is most effective when the MAP varies and IOP is not controlled.

Entoptic visualization of the retinal vasculature near fixation.

The authors review (1) the range of techniques used to study the retinal vasculature near the fovea, (2) describe the need and rationale for noninvasive in vivo monitoring of the retinal vasculature, (3) present theoretic and practical considerations which show that entoptic visualization of the smallest capillaries near the fovea is optimized by a small short-wavelength source (1 mm or less) rotating at 3.5 hertz in a circular path (radius 2 mm) imaged in the plane of the eye's entrance pupil, and (4) discuss the feasibility of using these techniques as a research and clinical tool.

Entoptic evaluation of diabetic retinopathy.

PURPOSE: Studies using optimized entoptic viewing of the parafoveal retinal vasculature have shown that normal subjects see their own capillaries with greater detail in the fovea than seen typically in fluorescein angiography. The authors have extended these investigations to persons with diabetes to evaluate the sensitivity, specificity, and accuracy with which they can detect and locate their own parafoveal retinal defects untrained. METHODS: A vascular entoptoscope using Maxwellian view optics creates a high-contrast entoptic view of retinal vasculature abnormalities in the parafoveal area. Using a double-masked protocol, 70 patients with diabetes and 29 control subjects described, drew, and quantified their entoptic image. These entoptic records were compared to angiograms and color photographs obtained immediately after the entoptic evaluation. RESULTS: Angiograms or color photographs or both showed that 61 of 70 patients with diabetes had retinal defects (e.g., microaneurysms or exudates or both) within the field of view of the Vascular Entoptoscope (8.1 degrees or 11.6 degrees circular field depending on the Vascular Entoptoscope used: parafoveal area subtends approximately 9.7 degrees). Of these 61 patients with diabetes, 51% (31) observed dark "spots" or "blobs" in the entoptic field corresponding to retinal defects in the angiograms or photographs or both. Seven (18%) of the 38 patients (9 patients with diabetes and 29 control subjects without defects in the entoptic field) said they saw something when angiograms or photographs or both showed nothing (false-positive). Thus, the sensitivity and specificity (using angiograms or photographs or both as the gold standard) with which untrained patients with diabetes detect their own parafoveal area defects are 51% and 82%, respectively. Superimposition of the entoptic image (as drawn by the patient) and the angiograms or color photography or both often showed excellent correspondence. Most (22 of 29) of the control subjects and more than half (40 of 70) the patients with diabetes were able to quantify the size of their foveal avascular zone (FAZ) from the entoptic view, whereas only 22 of 70 of the capillary loops defining the FAZ were visible in the optimal frame of the capillary phase of the fluorescein angiogram. As reported previously in a smaller sample, large FAZs often were associated with poor visual acuity. CONCLUSIONS: More than half the untrained patients with diabetes were able to visualize their own parafoveal retinopathy entoptically, and most untrained patients with diabetes and control subjects where able to quantify the size of their FAZ. Patients and control subjects without parafoveal defects rarely report defects not visible photographically. Patients can be trained to detect their defects. Clinical entoptic monitoring will require verification that patients can detect changes in their retinopathy. Entoptic testing is low cost, noninvasive, and can be performed as often as needed at no risk to the patient. It is, therefore, a promising research technique for subjective monitoring of the early natural history of parafoveal area disease processes.

Retinal fixation point location in the foveal avascular zone.

The site of normal fixation is often assumed to be centered in the foveal avascular zone (FAZ). This assumed anatomic relationship is used during photocoagulation therapy as an objective guide to avoid damaging critical retinal structures on or near fixation. With laser therapy being directed closer and closer to the center of the FAZ, the accuracy with which the center of the FAZ locates the retinal point of fixation becomes an important therapeutic issue. Using an optimized technique for visualizing the retinal vasculature entoptically, the authors determined the location of the retinal point of fixation with respect to the foveal area vasculature in 26 eyes of 14 healthy subjects. In 23 eyes (12 subjects), a traditional FAZ was observed, the other three eyes (two subjects) had capillaries near or crossing the center of fixation. Of the 23 eyes with a traditional FAZ, 20 had centers of fixation located eccentric to the center but in the FAZ, (average deviation from the center of the FAZ, 66.5 +/- 49.5 microns) with the direction of deviation from the FAZ center appearing random. Consequently, when following protocols that advocate photocoagulation treatment with spot centers closer to the FAZ center than 300 microns, the center of the FAZ is a poor locator of a subject's retinal point of fixation. When using the FAZ as a reference, the resulting uncertainty in the location of the subject's retinal point of fixation increases the probability of significant damage to the actual point of fixation by up to 20%.

Is there an ethnic difference in the effect of risk factors for diabetic retinopathy?

Mexican Americans have an increased prevalence and incidence of non-insulin-dependent diabetes mellitus (NIDDM). In addition, Mexican American diabetic subjects have an increased prevalence of retinopathy relative to Caucasian diabetic subjects. In Mexican American diabetic subjects, established risk factors may have a stronger effect on diabetic retinopathy, compared to Caucasian diabetic subjects. In this report, we compare the effect of established risk factors (age at examination, gender, age at diagnosis of diabetes, duration of diabetes, glycemia, type of therapy, systolic and diastolic blood pressure, and hypertension prevalence) between Caucasian diabetic subjects (n = 478), a low-risk population for NIDDM (Wisconsin Epidemiologic Study of Diabetic Retinopathy), and Mexican American diabetic subjects (n = 231), a high-risk population for NIDDM (San Antonio Heart Study). Retinopathy was classified into two categories (any or none) as assessed by seven standard stereoscopic retinal photographs read at the University of Wisconsin Reading Center. Mexican American diabetic subjects in Texas had an increased prevalence of any retinopathy (odds ratio = 1.71, 95% confidence interval: 1.25, 2.34), compared to Caucasian diabetic subjects in Wisconsin. Longer duration of diabetes, more severe glycemia, earlier age at diagnosis, and insulin therapy were associated with diabetic retinopathy in both Mexican Americans and Caucasians. Socioeconomic status was not associated with prevalence of retinopathy. Moreover, the effect of risk factors for retinopathy was similar in both ethnic groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoproteins in human subretinal fluids.

The lipids in the subretinal fluid of rhegmatogenous retinal detachment are observed mainly in the albumin position following electrophoresis on agarose film. The lipoprotein in the subchoroidal fluid of the same eye is alpha-lipoprotein. The albumin-like lipoprotein in subretinal fluid has no reaction with the antiserum samples specific to alpha-lipoprotein and beta-lipoprotein. Instead, an apoprotein of serum alpha-lipoprotein with slow electrophoretic mobility was observed in subretinal fluid. Heterogeneous degradation products of serum lipoproteins were seen in the subretinal fluid of exudative retinitis, different from the subretinal fluid of rhegmatogenous retinal detachment and uveal effusion.

Experimental retinal vascular occlusion. I. Pathogenesis of central retinal vein occlusion.

In 45 eyes of rhesus monkeys, five types of central retinal vascular occlusion were produced by lateral orbitotomy: group 1, central retinal vein occlusion (CRVO) alone; group 2, CRVO with simultaneous central retinal artery (CRA) occlusion; group 3, CRVO with transient clamping of the CRA for either 2 to 2 1/2 hours (group 3A) or 6 to 7 1/2 hours (group 3B); and group 4, CRVO with segmental retinal ischemia. The eyes were examined by fundus photography and fluorescein angiography for up to nine months. Group 1 developed venous stasis retinopathy (VSR) and group 3B hemorrhagic retinopathy (HR). In group 4 the ischemic and nonischemic segments of the retina developed segmental HR and VSR, respectively. Groups 2 and 3A developed neither VSR nor HR. Retinal capillary obliteration occurred in groups 2 and 3B and in the ischemic part of group 4, starting one to three weeks after the occlusion and progressing thereafter. These studies indicate that clinically co-called CRVO consists of two distinct entities: VSR and HR, with retinal ischemia playing an important role in the production of HR. On the basis of the present and other available information, the pathogenesis of CRVO was concluded to be multifactorial.

Gelatin implants in scleral buckling procedures.

The use of gelatin has been evaluated in a series of 59 retinal surgical procedures over a five-year period. When used as a "trapdoor" alone, we conclude that gelatin works as well as any of the currently employed materials for simple cases. The technique gave a 90% primary reattachment rate, which was increased to 100% reattachment by subsequent surgery or photocoagulation. It also gave a desirable absorbable feature in very anterior or very posterior lesions. Used as a meridional implant and combined with one or two layers of solid silicone, the gelatin has proved to be extremely useful in closing holes that were highly elevated or significantly "fish mouthing." We wish to emphasize the value of this use as a meridional implant combined with silicone in complex cases.

Source of subretinal fluid on the basis of ascorbate analyses.

Biochemical analyses of subretinal fluid revealed a consistently high ascorbate level in the subretinal fluid of patients with rhegmatogenous retinal detachment. The average values and SDs of ascorbate in anterior chamber aqueous humor, subretinal fluid, and blood were 14.7 +/- 1.8, 27.4 +/- 2.1, and 1.8 +/- 0.2 mg/dL, respectively. The ascorbate concentration in subretinal fluid was always higher than that in aqueous humor. The high ascorbate level in subretinal fluid led to the hypothesis that aqueous humor contributes to the formation of subretinal fluid. Presumably and constant absorption of subretinal fluid by the choroid directs a portion of the aqueous humor from the posterior chamber into the subretinal space. The posterior movement of aqueous humor causes reduced ascorbate concentration in the anterior chamber and relative hypotony of eyes with rhegmatogenous retinal detachment. Closing the retinal break results in an interruption of the posterior movement of aqueous humor and rapid absorption of the remaining subretinal fluid by the choroid.

Vitreous membranes. A light and electron microscopical study.

Patients with pigmented vitreous membranes were subjected to partial vitrectomy, and the membranes were studied by light and electron microscopy. Two yellow ochre membranes from eyes removed at autopsy were also examined. The membranes were composed of degenerating red cells and a delicate matrix of collagen. Phagocytic cells of uncertain origin and migrating retinal pigment epithelial cells were present in some of the membranes. Vascular channels were observed in only two cases, in which the membranes had clinical features different from those in the remaining cases. The development of new techniques of vitrectomy and the relatively normal clinical appearance of the posterior pole of the retina in these cases both suggest the potential clinical value of vitreous membrane excision. Additional histopathologic studies of vitrectomy specimens will enhance our understanding of the indications for this procedure.

Albumin-bound bilirubin in subchoroidal fluid.

The most unique property of subchoroidal fluid was found to be the high bilirubin level. One distinct yellow band in the same position as albumin was observed when it was subjected to electrophoresis on agarose film. The yellow compound was very soluble in chloroform. Its identity to bilirubin was confirmed by its absorption maximum at 445 nm, and a positive reaction with Ehrlich's diazo reagent. Subretinal fluid and liquid vitreous often had a yellowish appearance after ocular hemorrhage. However, their bilirubin level was not elevated above that of serum. Our data indicated that the degradation of RBCs may be an important causative factor of persistant detachment.

Retinal blood flow derived from dye dilution curves: Televised fluorescein angiography.

A television system was used to record retinal fluorescein dilution curves. In pigs, fluorescein was injected intravenously (IV), into the left ventricle (ILV), and ILV during bilateral carotid occlusion (ILVco). Dye dilution curves from points on a retinal-artery-vein pair, from two points on a single artery, and from two points on a single vein were recorded by a storage oscilloscope, using two photodetectors positioned over the television image of the vessels. Dye curves were less dispersed following ILV than following IV injections, and were irregular following ILVco injection. The dye appearance time was shortest after injection with ILV and progressively longer with ILVco and IV. The artery-vein mean transit time was greatest during carotid occlusion. Retinal blood flow in a venous segment was calculated to be 0.149 +/- 0.037 mi/min. This value was reproducible following both IV and ILV injections but could not be obtained following ILVco due to irregularity of the curves. It was in the same range as that found (0.095 +/- 0.011 ml/min), using the radioactively labeled microsphere technique. The system was subsequently tested in humans and was found to give reproducible dye curves. The usefulness of the system as a clinical tool is presently being explored.

Echographic characteristics of benign orbital schwannomas (neurilemomas).

We examined two patients with orbital schwannomas (neurilemomas). The echographic findings, including a sharply outlined capsule, a well-defined central cystic space within the tumor with very low internal reflectivity surrounded by smaller cysts with variable reflectivity, slight or no compressibility, and blood flow, should help to differentiate these benign tumors from other orbital lesions. Histologic examination showed a combination of Antoni type A (dense and cellular) and Antoni type B (loose, edematous, or necrotic) patterns.

Hypopyon uveitis following panretinal photocoagulation.

The authors describe the rare complication of hypopyon uveitis following panretinal photocoagulation. A 55-year-old man with a history of diabetes mellitus and previous repair of a retinal detachment by scleral buckle and vitrectomy was referred to the authors after a hypopyon uveitis developed following supplemental panretinal photocoagulation. The patient was treated with frequent topical steroids in addition to periocular injection of steroids with resolution of the inflammation. Risk factors for anterior segment ischemia, such as a history of a scleral buckle, may predispose diabetic patients to the complication of hypopyon uveitis following panretinal photocoagulation.