The decreasing incidence and severity of retinopathy of prematurity.

PURPOSE: We sought to determine whether the incidence of retinopathy of prematurity (ROP) at our institution has changed since the Cryo-ROP recruitment period 10 years ago. METHODS: We determined the incidences of threshold ROP, prethreshold ROP, less-than-prethreshold ROP, and no disease for each of 3 birth weight classes (<750 g, 750 to 999 g, and 1000 to 1250 g) of infants born between July 1, 1995, and June 30, 1996, and cared for in the Vanderbilt Neonatal Intensive Care Unit. We then compared these with the rates from our institution during the Cryo-ROP study recruitment period (January 1, 1986, to November 30, 1987). RESULTS: The current incidence and severity of ROP have decreased substantially overall and for each weight group compared with the 1986-87 incidence (P < .001, Cochran-Mantel-Haenszel test). The incidence of "any ROP" decreased by 27% for infants with birth weights less than 750 g, by 51% for infants 750 to 999 g, and by 71% for infants 1000 to 1250 g. The incidence of "prethreshold or greater ROP" decreased by 70% for the 750 to 999 g and 77% for the 1000 to 1250 g weight groups. Although the decrease in "prethreshold or greater ROP" was not as dramatic (25%) for the infants less than 750 g, only 1 infant (10%) progressed to threshold disease in this group, whereas 7 (47%) did in 1986-87. The incidence of threshold ROP decreased by 84% for infants less than 750 g and by 66% for infants 750 to 999 g. No infant with birthweight greater than 999 g progressed to threshold ROP. CONCLUSIONS: The incidence of all levels of ROP has decreased substantially for all infants with birth weights less than 1251 g at Vanderbilt University Medical Center during the past decade. Putative factors responsible for this decrease may include surfactant use, continuous pulse oximetry, aggressive use of antenatal steroids, and improved neonatal nutritional support.

The topographic distribution of the first sites of diabetic retinal neovascularization.

PURPOSE: To examine the topographic distribution of the origin of diabetic retinal neovascularization. METHODS: The eyes of 3,121 patients with background diabetic retinopathy were investigated. These patients were volunteers in systemic medical therapy experiments. Color stereo photographs were obtained annually. The first retinal neovascularization sites were identified and the distances from the optic nerve measured. RESULTS: In 1 year, neovascularization originated in 282 eyes. The superotemporal quadrant, at 6 mm from the optic disk, was the most frequent initial site. CONCLUSIONS: The first retinal neovascularization sites cluster around specific anatomic foci. This information should influence retinopathy monitoring protocols.

New discoveries in diabetes- and thyroid-related eye disease.

Although reports from Europe indicate a reduction in the incidence of diabetes-related visual loss, diabetic retinopathy continues to be the leading cause of blindness. One agent, vascular endothelial growth factor (VEGF), has been found to stimulate angiogenesis and may be the cause of diabetic neovascularization and visual loss. New research implies that the manipulation of the VEGF pathway may be able to prevent diabetic visual loss. Type I (insulin-dependent) and type II (non-insulin-dependent) diabetes mellitus are different disease processes. There have been few attempts in the past to differentiate the retinopathy associated with these two distinct disorders. Recent reports indicate that these disorders have different responses to ocular therapy. Thyroid orbitopathy combined with ocular hypertension can produce true glaucoma. Nevertheless, this requires a prolonged duration of orbitopathy and most patients who have this combination will improve and not develop permanent glaucomatous changes. Similarly, the majority of Graves' disease patients develop improved function over time; however, the psychologic sequelae continue after the disease process is in remission, which warrants further studies.

Diabetes- and thyroid-related eye disease.

There is significant morbidity associated with diabetes- and thyroid-related eye diseases. Many different ocular changes are associated with these endocrine disorders. Vitreous hemorrhage from diabetic neovascularization remains the leading cause of blindness, and several recent studies of the etiology of this disorder are of great importance. However, in addition, other research examined aspects of diabetic visual loss that are not blinding, and the prevention of such impairment became significant this past year. During this same interval, specific diagnostic criteria for thyroid ophthalmopathy were established and are included in this review; these findings will aid in future research and patient care.

The Vanderbilt Classification System in the evaluation of diabetic retinopathy patients treated with Alredase.

BACKGROUND: The Vanderbilt Classification System is a quantitative method of measuring features detected in diabetic retinopathy photographs. It does not require comparisons to preexisting standard photographs. This is the first report of the application of this system to a large-scale, multiple-medical-center drug trial. METHODS: This was a prospective, randomized, double-masked, placebo-controlled study that involved 74 medical centers. There were 3,679 out-patients followed for more that 4 years, with some observed for over 9 years. The Vanderbilt Classification System generated patient data for the Early Treatment Diabetic Retinopathy Study (ETDRS) and the Diabetes Control and Complication Trial (DCCT) scales. The deterioration rate was one variable used to assess drug effect. A comprehensive Quality Assurance Program evaluated intergrader and intragrader reliability. RESULTS: Target values for reliability and reproducibility were met or exceeded on all measures of agreement between photo readers and over time. Kappa statistics were 0.610 or greater, with most weighted kappa values greater than 0.810. This represents "almost perfect agreement" and compares favorably with previous reports from the ETDRS and DCCT. CONCLUSION: Diabetic retinopathy can be evaluated in a reliable and reproducible manner with the VCS. The VCS is unique in that it produces a quantitative analysis of retinal lesions. Subtle variations that might be influenced by systemic medications can be measured accurately with this technique.

Diabetes and thyroid-related eye disease.

During the past year, the results of the Diabetes Control and Complications Trial became available. This event is expected to influence all future diabetes eye disease research. For this reason, this article starts with a discussion of these results.

A quantitative system to evaluate diabetic retinopathy from fundus photographs.

PURPOSE: To evaluate a quantitative system to measure the early lesions of diabetic retinopathy seen in stereoscopic fundus photographs. METHODS: Using a quantitative classification system, photographs of 4657 eyes (7 stereo pairs of 35-mm slides per eye) were scored for 16 diabetic lesions. A single severity level (identical to the ETDRS Interim Scale) was calculated for each eye. The reliability of this technique, and its reproducibility by independent examiners, was evaluated for individual lesions and severity levels using percent agreement, kappa, and weighted kappa statistics. RESULTS: This quantitative technique demonstrated an "almost perfect" agreement (weighted kappa > or = 0.810) on all but one lesion by independent observers. For the severity levels, there was a 95.7% perfect agreement (kappa = 0.9428). The reproducibility of agreement over time was "almost perfect" on all but four lesions; with 88% perfect agreement (kappa = 0.8394) for severity levels. CONCLUSIONS: When used to evaluate the early lesions of diabetic retinopathy, the Vanderbilt Classification System is highly reliable between graders and over time. This system can gather quantitative data and evaluate incremental changes in an accurate, reproducible manner.

Diabetes and thyroid-related eye disease.

Diabetes and thyroid-related eye disease cause significant morbidity. Although these are endocrine disorders, they cause different ocular manifestations. Previously unexamined epidemiologic factors offer new insight to diabetic eye disease. The association of hyperglycemia, systemic medical therapy, and visual loss is reviewed. Although retinopathy remains the leading cause of blindness, multiple "nonretinal" diabetic ocular problems occur and how these correspond with retinopathy is examined. Thyroid-related eye disease, as seen in Graves' ophthalmopathy, is an autoimmune process. This is reexamined and new ultrasound techniques to measure disease activity are described. The advantage of therapies directed against these features is reported.

The natural history of the first clinically visible features of diabetic retinopathy.

Microaneurysms are the first features of human diabetic retinopathy that can be detected with common clinical techniques. These are found, most often, in photographic field 2 (that is, an area occupying 30 degrees of the ocular fundus centered on the middle of the macula). After the first microaneurysms develop, there will be a tendency for more to appear; however, over time many of the original microaneurysms will become no longer visible with clinical techniques, while other, newer, microaneurysms mature. After the onset of microaneurysms, several years may pass before any other diabetic retinopathic lesions develop. Lesions other than microaneurysms were uncommon in this study; the following is a list in decreasing frequency: retinal hemorrhages, soft exudates, IRMA, hard exudates, and venous beading. During the 4 years of this study, there were no other diabetic retinopathic lesions detected. The duration of insulin-dependent diabetes mellitus was related to the rate of change in microaneurysm counts. The age and sex of patients did not affect this rate of change. The accuracy of metabolic control, as determined by glycosylated hemoglobin levels, may influence this rate of change; however, this was detected only at the extremes of measurement in this study. The equipment available to most ophthalmologists can detect the earliest clinical aspects of diabetic retinopathy. These features can be quantified in a reproducible manner with standardized photographic techniques to permit satisfactory data analysis.

Serum angiotensin converting enzyme in diabetic patients.

Serum angiotensin converting enzyme (ACE) levels are higher in patients with diabetes mellitus than in many others. Techniques are available to grade different degrees of diabetic retinopathy, which can demonstrate a relationship between ACE and diabetic retinopathy. In this study, patients with diabetic retinopathy had higher serum ACE levels (6.3 +/- 0.2) than nondiabetic patients (4.3 +/- 0.5) (p < 0.001). In addition, the mean serum ACE level in diabetic patients with nonproliferative retinopathy (5.55 +/- 0.4) was less than that in diabetic patients with proliferative retinopathy (6.63 +/- 0.25) (p = 0.02). Due to the variability in individual serum ACE levels and the frequent use of ACE inhibitors by hypertensive diabetics, these techniques are not suitable for retinopathy screening programs. However, the graded relationship demonstrated by these data may have relevance for the pathophysiology of diabetic retinopathy.

Retinal vascular abnormalities in patients with coarctation of the aorta.

Pulsatile three-dimensional retinal arteriolar tortuosity has been previously reported in about 50% of patients with coarctation of the aorta. In a contemporary series of 20 patients with coarctation of the aorta, none exhibited this characteristic retinal vascular abnormality. Our findings suggest that the retinal vascular abnormalities in patients with coarctation of the aorta represent secondary hemodynamic changes. The prevalence of these abnormalities may be decreasing because of earlier surgical repair of coarctation.

Intraocular tumor from disseminated histoplasmosis.

We identified and treated a solid, growing fungal tumor mass in a patient with disseminated histoplasmosis. Although the most commonly reported intraocular lesions from disseminated histoplasmosis are areas of inactive chorioretinal scars or areas of localized subretinal neovascular membrane formation, a focus of active fungal growth needs to be ruled out in all such cases. When a solid tumor mass is identified, the most effective way of preserving vision is with systemic antifungal therapy.

Retinopathy of prematurity in infants with cyanotic congenital heart disease.

We undertook a study of premature infants with cyanotic congenital heart disease to determine whether these infants develop retinopathy of prematurity despite a persistent hypoxemic state. Using the computerized registry of the neonatal intensive care unit of Vanderbilt University Medical Center, Nashville, Tenn, we identified six premature infants (less than 37 weeks' gestational age, with birth weights of 1100 to 2050 g) with cyanotic congenital heart disease who survived the neonatal period and underwent ophthalmologic evaluation. Review of their charts revealed that three of six infants developed retinopathy of prematurity (two had grade 1 and one had grade 3 disease), but none required treatment. Our data support the findings of other investigators that elevated arterial oxygen tension is not the sole factor leading to the development of retinopathy of prematurity. Premature infants with cyanotic congenital heart disease can develop retinopathy of prematurity despite persistent hypoxemia. Cyanotic premature infants should be screened for retinopathy of prematurity with the same thoroughness as other premature infants.

The effect of panretinal photocoagulation on optic nerve cupping.

Panretinal photocoagulation (PRP) can produce damage to all layers of the retina, including the nerve fiber layer. The hypothesis that these changes in the nerve fiber layer may alter the contour of the optic disc and change the cup-to-disc (C/D) ratio was tested. In a masked retrospective study, the authors evaluated the stereoscopic disc photographs of 100 patients with proliferative diabetic retinopathy (PDR) before and 1 year after undergoing PRP. The fellow untreated eyes were used as controls. Neither argon nor xenon PRP produced a significant change in the C/D ratio.

Chorioretinitis in the contralateral eye of a patient with Acanthamoeba keratitis.

Chorioretinitis developed in the right eye of a patient with contact lens-associated Acanthamoeba keratitis in the left eye during an acute exacerbation of the keratitis. This chorioretinitis may have resulted from hematogenous dissemination from his corneal infection.

Visual impairment following radial keratotomy. A cluster of cases.

Thirteen patients who underwent radial keratotomy developed complications leading to visual impairment. Three eyes were legally blind. Two groups of complications were seen: those common to surgical procedures involving the eye--optic atrophy, infections, cataract and retinal detachment, and those unique to radial keratotomy--complete failure of the procedure, marked undercorrection, marked overcorrection, and induced astigmatism. Symptoms due to anisometropia were prominent in the latter group who considered themselves visually disabled by the surgery. Radial keratotomy, like all surgical procedures, is liable to complications that may lead to visual impairment, blindness, or loss of an eye.