Joseph E. Robertson

The Age-Related Eye Disease Study (AREDS) system for classifying cataracts from photographs: AREDS Report No. 4

PURPOSE To describe the system for grading cataracts from photographs in the Age-Related Eye Disease Study (AREDS). METHODS The system for grading cataracts in AREDS uses photographs taken in a standardized fashion with specially modified cameras at 11 clinical centers. The photographs are evaluated by graders for quality and cataract severity at a central reading center. The area of lens involvement is used to assess the severity of cortical and posterior subcapsular opacities. Optical density of nuclear opacity is graded against a series of seven standard photographs. Contemporaneous variability in grading is evaluated periodically by having a second examiner regrade a subset of the photographs. Temporal variability is assessed by annually regrading a subset of photographs. RESULTS Photographs of 925 eyes, most with no or early lens opacities, were regraded to assess intergrader reliability. For cortical opacities, there was an absolute difference of 10% or greater of area involved in 1.9% of the replicate gradings. For posterior subcapsular opacities an absolute difference of 5% of area involved was noted in 2.8% of the regraded photographs. For nuclear opacities, absolute differences of 1.5 or more steps were observed in 0.6% of eyes. There was little evidence of temporal drift in grading any of the three types of opacity during four annual regrades. CONCLUSIONS We have demonstrated a high degree of reliability in grading the severity of lens opacities in a large study cohort with mostly early lens changes, the type of cohort most likely to be entered in clinical trials involving cataract prevention. The Age-Related Eye Disease Study System for Classifying Cataracts From Photographs could be useful in studies where there is a need to standardize data collection over time and across different data collection sites. Limitations of the system include the cost of implementation and, currently, the limited amount of data on grading reproducibility for more advanced lens opacities.

Cultured human retinal pigment epithelial cells express basic fibroblast growth factor and its receptor

Basic fibroblast growth factor (bFGF) has been implicated in the maintenance of neuronal differentiation, the induction of neovascularization and intravitreal proliferative diseases. We have found that human retinal pigment epithelial (RPE) cells grown in vitro transcribe the bFGF gene and synthesize a peptide that crossreacts with anti-bFGF antibodies. In culture, these cells appear to release activity with biological and biochemical properties similar to bFGF. RPE cells have specific bFGF receptors and proliferate in response to bFGF. Thus, it is possible that the RPE cell is an important source of retinal bFGF and may respond to bFGF in an autocrine manner.

Somatostatin analogues inhibit angiogenesis in the chick chorioallantoic membrane

The mechanism responsible for alterations in tumor growth following administration of somatostatin analogues is unknown. Somatostatin analogues, SMS 201-995 and RC-160, have demonstrated the potential to inhibit both tumor growth and vascularity, in vivo and in vitro. We hypothesized that SMS and RC-160 inhibit angiogenesis and this inhibition may alter tumor growth. To test this hypothesis, 2 mm methylcellulose disks containing concentrations of SMS 201-995 and RC-160 at 0, 0.5, 2.5, or 50 micrograms per disk, were implanted on the chorioallantoic membrane (CAM) of 6- to 7-day-old shell-less chick embryos. Inhibition of blood vessel growth in the region of the disk was visually assessed 24-36 hr following disk implantation and graded (0-4) based on the radius of the zone of inhibition from the center of the disk. The overall incidence of inhibition for the somatostatin analogues at concentrations of 0.5, 2.5, and 50 micrograms per disk was 13, 56, and 61% for SMS and 27, 49, and 68% for RC-160, respectively. Overall incidence of inhibition for the positive (inhibitory) control was 70.5% and those for buffer (negative) controls were 3-14%. Somatostatin analogues were associated in a dose-related fashion with both a greater percentage of inhibition of blood vessel growth and an increased grade of inhibition. Inhibition of angiogenesis may be a mechanism responsible for the tumor regression observed in vivo following SMS or RC-160 therapy.

Results and Complications of Pneumatic Retinopexy

Fifty-one patients with primary rhegmatogenous retinal detachment (RD) were treated by pneumatic retinopexy. The overall success rate for reattachment with one operation was 63%. Of the 34 phakic eyes, 25 (74%) were reattached; of the 17 aphakic or pseudophakic eyes, seven (41%) were reattached (P less than 0.05). Postoperative complications included the development of new tears (22%), inadequate closure of the original tear, shifting and delayed absorption of subretinal fluid, and opening of previously closed tears. Pneumatic retinopexy is a valuable new technique; however, careful patient selection and postoperative management is required.

Acute Retinal Necrosis Caused By Reactivation of Herpes Simplex Virus Type 2

Acute retinal necrosis is a severe form of necrotizing retinitis. Acute retinal necrosis has been demonstrated to be caused by varicella-zoster virus and herpes simplex virus type 1. We treated three patients with acute retinal necrosis apparently caused by recrudescence of latent herpes simplex virus type 2. Primary viral infection was probably congenital, with documented perinatal herpes simplex virus type 2 infection in two patients. Bilateral chorioretinal scars were present in two patients, neither of whom had a history of ocular herpetic infection, suggesting that earlier subclinical chorioretinitis had occurred. In each case, periocular trauma preceded the development of retinitis by two to three weeks. These cases are evidently caused by trauma-induced reactivation of latent virus rather than the onset of a primary infection.

Retinal pigment epithelial cells produce interleukin-1β and granulocyte-macrophage colony-stimulating factor in response to interleukin-1α

The retinal pigment epithelium (RPE) is clinically involved in diverse ocular inflammatory diseases. Because perturbed RPE cells produce a variety of inflammatory substances, RPE cells may play an integral part in these diseases. Interleukin-1 (IL-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are pleiotropic cytokines with the ability to trigger numerous inflammatory responses. This report shows that cultured human RPE cells synthesize interleukin-1 β (IL-1β) and GM-CSF in response to the potentially inflammatory cytokine, IL-1α, but not to E. coli endotoxin. Control RPE cells made little or no mRNA or protein for either IL-1β or GM-CSF. Upon stimulation of the cells by IL-1α, both IL-1β and GM-CSF mRNAs were readily apparent by 3 hours, persisted for over 24 hours, and were translated into immunologically detectable proteins. GM-CSF protein was secreted into the culture medium, whereas IL-1β protein remained cell associated. The IL-1α-induced mRNA and protein production were inhibited ...

Visual acuity of eyes after vitrectomy for retinopathy of prematurity : Follow-up at 5 1/2 years

PURPOSE To provide long-term follow-up on the structural status and visual function at 5 1/2 years of age for 128 eyes of 98 infants who participated in the multicenter randomized clinical trial of cryotherapy for retinopathy of prematurity in whom total retinal detachment developed from retinopathy of prematurity (ROP) by the 3-month study examination. Fifty-four patients had lensectomy-vitrectomy procedures in one or both eyes before 1 year of age (n=72 eyes), and 44 patients did not (n=56 eyes). METHODS When the children were 5 1/2 years of age, an eye examination was performed and residua of ROP was assessed. Recognition acuity (Early Treatment of Diabetic Retinopathy Study chart) and grating visual acuity (Teller acuity card procedure) assessments were undertaken by testers who were masked to the status of each of the childs eyes. RESULTS At least partial retinal attachment was present at 5 1/2 years in 21% compared with 28% at 1 year of age (not significant). All except one of the eyes tested at 5 1/2 years had vision limited to light perception or no light perception, regardless of whether a vitrectomy had been performed. One eye that underwent vitrectomy had minimal pattern vision. The two eyes that were reported previously to have minimal pattern vision at 1 year of age were blind at the longer-term follow-up. CONCLUSIONS The poor visual outcome after a lensectomy-vitrectomy procedure for retinal detachment due to ROP demands that emphasis be placed on prevention of retinal detachment in premature infants.

Vitreous hemorrhage is a common complication of pediatric pars planitis

OBJECTIVE To report the prevalence of vitreous hemorrhage in pars planitis and to compare the prevalence of hemorrhage for children and adults with the disease. DESIGN A retrospective, cross-sectional observational study. PARTICIPANTS One hundred eighteen consecutive patients with pars planitis who were evaluated at the Oregon Health and Science University Uveitis Clinic between September 1985 and April 2000. METHOD A review of clinical records. MAIN OUTCOME MEASURES For all patients, we recorded presence or absence of vitreous hemorrhage, as well as laterality and cause. Children were defined as being age 16 years or younger at diagnosis, and adults were defined as being aged 17 years or older at diagnosis. RESULTS Fourteen percent of patients with pars planitis experienced vitreous hemorrhage. Persons with hemorrhage were significantly younger at the time of disease diagnosis than persons without hemorrhage (P = 0.040). The difference in prevalence of vitreous hemorrhage between children (28%) and adults (6%) was statistically significant (P = 0.003). The difference in prevalence of hemorrhage as a presenting feature between children (20%) and adults (1%) was also statistically significant (P = 0.001). CONCLUSIONS Children with pars planitis are more likely than adults to experience vitreous hemorrhage. Pars planitis should be considered in the differential diagnosis of pediatric vitreous hemorrhage.

Expression of Growth Factor Mrna in Rabbit Pvr Model Systems

Proliferative vitreoretinopathy (PVR) involves the formation of intravitreal fibrocellular membranes which may lead to traction retinal detachment and blindness. The cellular component of epiretinal membranes originates from the proliferation and migration of cells within the eye. Several growth factors and other cytokines are plausible candidates for directing the processes leading to membrane formation. A reproducible animal model is needed for experimental studies of cytokine expression during PVR induction or treatment. We found that intravitreal injection of > 10(6) mixed mononuclear leukocytes or adherent monocytes along with a trans-scleral incision through the pars plana leads to the development of PVR-like disease in rabbit eyes. The severity of the disease was related to the number of monocytes injected. Typically, organized membranes extending from the incision toward the optic nerve formed within one week. Progression to extensive traction retinal detachment required 1 to 4 weeks. Injection of up to 5 x 10(6) lymphocytes or freeze-thaw killed monocytes was ineffective, and coinjecting 100 micrograms endotoxin with the monocytes did not result in enhanced disease. The histological appearance of the epiretinal membranes was similar to human PVR membranes. Macrophage, cytokeratin-positive (epithelial), and fibroblast-like cells were present. Northern blot analysis of RNA extracted from the rabbit membranes revealed the presence of mRNA for acidic fibroblast growth factor (aFGF). Acidic FGF mRNA was not expressed by the injected monocytes. A comparable level of aFGF mRNA and also mRNAs for basic FGF, platelet-derived growth factor-B, and transforming growth factor beta were found in epiretinal membranes induced by a scleral incision in association with cryopexy.(ABSTRACT TRUNCATED AT 250 WORDS)

Recognition of posterior scleritis and its treatment with indomethacin

Abstract: Posterior scleritis is a rare disease, the clinical signs of which may vary. There is no consensus on the appropriate method of treatment for this disease. Some have advocated treatment with nonsteroidal antiinflammatory drugs, whereas others have reported variable success with potentially more toxic therapy. Patients with posterior scleritis constitute approximately 1% of the uveitis clinic population at the Casey Eye Institute in Portland, Oregon. The cases of 6 patients with posterior scleritis, the diagnosis of which was elusive, are reported. Posterior scleritis was generally confirmed by ultrasound examination. Each of the patients responded to treatment with indomethacin, which was usually the sole method of nontopical therapy. Thus, recognition of this relatively rare disease had marked implications for treatment.