ROP surgery and ocular circulation.

PURPOSE: Visual results following vitreoretinal surgery for stages 4 and 5 retinopathy of prematurity are often disappointing, even when anatomic results are good. This poses the question whether the surgery or the post-operative care causes the optic atrophy. A hypothesis is proposed that ocular perfusion pressure (mean blood pressure minus intraocular pressure) during or after surgery may be too low to provide adequate ocular blood flow. METHODS: This report analyses the published results of retinopathy of prematurity surgery, the techniques used, as well as data about blood pressure and intraocular pressure in premature infants. RESULTS: Mean blood pressure in conscious premature infants is low and labile; it falls further under anaesthesia. Pre-operative intraocular pressure in retinopathy of prematurity patients is unknown, but intraocular pressure during vitrectomy is elevated, and likely elevated postoperatively. CONCLUSIONS: Conditions during and after vitreoretinal surgery for retinopathy of prematurity are conducive to low ocular perfusion pressure and consequent ischaemia of the retina and optic nerve, which can contribute to poor visual results. Improved monitoring and control of ocular perfusion pressure is warranted.

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.

Entoptic foveal avascular zone measurement and diabetic retinopathy.

BACKGROUND: Entoptic visualization of the foveal avascular zone (FAZ) provides a noninvasive method for measurement of the FAZ. To determine if repeatability of measurement with this technique is good enough to monitor changes in diabetic retinopathy, we quantify (1) the repeatability of entoptic FAZ measurement in healthy subjects and (2) the relationship between measured FAZ diameter and the severity of retinopathy. METHODS: (1) To determine FAZ measurement repeatability, 10 healthy adults entoptically measured their FAZ diameters in 11 separate testing sessions. (2) In a separate experiment, 53 patients with varying levels of diabetic retinopathy and 21 control subjects used a vascular entoptoscope to measure their FAZ diameters. RESULTS: The disease-related increase in FAZ diameter is large (approximately 400 microm) compared to the repeatability of the entoptic measurement within a subject (SD approximately 35 microm). CONCLUSION: Entoptic measurements have the repeatability necessary to reliably monitor increases in FAZ diameter of the magnitude of those induced by diabetes.

Retinal pigment epithelial dysfunction in human immunodeficiency virus-infected patients with cytomegalovirus retinitis.

OBJECTIVE: Prior clinical observations led the authors to examine electrophysiologic measures of retinal (electroretinogram [ERG]) and retinal pigment epithelial (electro-oculogram [EOG]) function in patients infected with human immunodeficiency virus (HIV) who either had or did not have cytomegalovirus (CMV) retinitis in order to determine if the ERG or EOG measures were differentially affected in CMV retinitis. DESIGN: Cross-sectional study. PARTICIPANTS: Forty-one HIV-infected patients (20 with and 21 without CMV retinopathy) were evaluated. INTERVENTION: ERGs and EOGs were recorded. Patients' fundi were evaluated by indirect ophthalmoscopy or fundus photography. MAIN OUTCOME MEASURES: The ERG a- and b-wave amplitudes and EOG light/dark amplitude ratio (L/D ratio) from the eyes of all patients were compared with values 2 standard deviations from the mean of a normal sample. The area of the retinal lesions was estimated from fundus photographs or from careful drawings made during indirect ophthalmoscopy. RESULTS: The majority of the eyes (64.5%) of the patients with CMV retinitis had subnormal L/D ratios, and most eyes (95%) of patients without CMV retinitis had normal L/D ratios. Only six eyes (four with and two without CMV retinopathy) had subnormal a-wave amplitudes, and there was no significant correlation between a-wave amplitude and the L/D ratio for patients with CMV retinitis. Most eyes (80.6%) of the patients with CMV retinitis had subnormal b-wave amplitudes, but there was no significant correlation between b-wave amplitude and L/D ratio in the patients with CMV retinitis. In three patients with CMV retinitis selected to exemplify the range of effects on the ERG and EOG, the b-wave amplitude loss was roughly proportional to the area of retina visibly affected in indirect ophthalmoscopy. One patient had a nonrhegmatogenous retinal detachment. CONCLUSIONS: Middle retinal function, as reflected in the b-wave amplitude, and retinal pigment epithelial function, as reflected in the L/D ratio, were both compromised in CMV retinitis, but the effect on function in the two layers of the retina appeared independent because there was no significant correlation between the L/D ratio and b-wave amplitude. The decrease in L/D ratio was not secondary to loss of photoreceptor function and probably represents a dysfunction of the retinal pigment epithelium because there was no significant correlation between a-wave amplitude, which was normal in most cases, and L/D ratio. The inner retinal pathology of CMV retinitis is visible clinically and was associated with decreases in b-wave amplitude in this and previous studies. The significant independent retinal pigment epithelial dysfunction demonstrated in this study may be an important predisposing factor to retinal detachment in CMV retinitis.

Lack of efficacy of light reduction in preventing retinopathy of prematurity. Light Reduction in Retinopathy of Prematurity (LIGHT-ROP) Cooperative Group.

BACKGROUND: Hospital-nursery lighting has been suggested as a factor in causing retinopathy of prematurity. Despite ongoing debate, a causal relation has not been established. METHODS: We conducted a prospective, randomized, multicenter study of the effects of light reduction on 409 premature infants with birth weights of less than 1251 g and gestational ages of less than 31 weeks. Two hundred five infants were exposed to reduced light, and 204 to typical nursery lighting. The amount of light reaching the infants' eyes was reduced within 24 hours after birth by placing goggles on the infants that reduced visible-light exposure by 97 percent and ultraviolet-light exposure by 100 percent. The babies wore the goggles until 31 weeks' postconceptional age or 4 weeks after birth, whichever was longer. Once the goggles were removed, ophthalmologists masked to the treatment assignments assessed the infants for retinopathy of prematurity at least biweekly for up to 13 weeks. RESULTS: There were 188 infants in the group that wore goggles and 173 in the control group who survived and were available for follow-up. The mean birth weights were 906 g in the goggles group and 914 g in the control group; the mean gestational ages were 27.4 weeks and 27.2 weeks, respectively. The mean ambient-light level adjacent to the infants' faces was 399 lux for the goggles group and 447 lux for the control group. Retinopathy of prematurity was diagnosed in 102 infants (54 percent) in the goggles group and 100 (58 percent) in the control group (relative risk, 0.9; 95 percent confidence interval, 0.8 to 1.1; P=0.50). CONCLUSIONS: A reduction in ambient-light exposure does not alter the incidence of retinopathy of prematurity.

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.

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.

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.

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.

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)

Psychophysical measurement of the size and shape of the human foveal avascular zone.

We have examined two psychophysical procedures for assessing the size and shape of the human foveal avascular zone (FAZ). Both procedures used a Maxwellian view system with a rotating beam to create a high contrast entoptic view of the retinal vasculature. Most subjects readily report a clear avascular zone surrounding their fixation point. The size of this FAZ was measured by (a) reducing the circular Maxwellian view field stop until it appeared to coincide with the edge of the FAZ, and (b) by tracing the boundary of the FAZ with a point source. Consistent with earlier angiographic and anatomical studies, the first method (N = 34 eyes) showed a mean FAZ diameter of 0.736 mm (area 0.42 mm2). FAZ diameter ranged from 0.46 to 1.13 mm (area 0.166-1.00 mm2) and the FAZ from the right and left eyes of each individual subject were very similar (r2 = 0.863). The tracing technique (n = 24 eyes) showed that FAZ's were generally not spherical but well fit by ellipses with, on average, a major axis 17% longer than the minor axis. The maximum diameters of the FAZ tracings were very similar and significantly correlated with the circle diameters matched to the FAZ in experiment 1.

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.

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%.

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.

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.

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)

Experimental retinal vascular occlusion. II. A clinico-pathologic correlative study of simultaneous occlusion of central retinal vein and artery.

After experimentally occluding the central retinal vein and artery simultaneously at their point of entry into the optic nerve, acute retinal necrosis occurred, but not hemorrhagic retinopathy. In the retinal vasculature, stagnation of blood flow and thrombosis with subsequent recanalization was noted. The necrosis was extensive in the inner retinal layers but focal in the outer retinal layers. The internal limiting membrane was detached and disrupted in every case. Following the post-edematous stage, numerous micro and macroretinal cysts appeared. The peripheral retina showed much less ischemic changes. A clinico-pathologic correlation was made.

Experimental retinal vascular occlusion. III. An ultrastructural study of simultaneous occlusion of central retinal vein and artery.

The retinal changes following the simultaneous occlusion of retinal vessels were examined at an ultrastructural level. The preservation of endothelial cells that prevented leakage of blood and horseradish peroxidase tracer material in the surrounding retinal tissues explained the lack of hemorrhages observed clinically. Mueller cell death resulted in severe structural disorganization of the retina, with disruption of the inner limiting membrane, involvement of the outer retinal layers, and fleurette formation. The retinal macrocysts were derived from ischemic infarction.