The risk of glaucoma in pseudoexfoliation syndrome.

PURPOSE: To determine the conversion rate of pseudoexfoliation syndrome (PEX) to pseudoexfoliative glaucoma or treated ocular hypertension. METHODS: Retrospective community-based study of newly diagnosed cases of PEX syndrome in all residents of Olmsted County, Minnesota between 1976 and 1991. The end point was considered the initiation of therapy, which included patients with glaucoma (optic disc damage or visual field defects), or with elevated intraocular pressure (IOP) >21 mm Hg in the presence of risk factors; the subsequent development of damage in the latter group was also determined. RESULTS: Two hundred fifty-five patients (318 eyes) had newly diagnosed PEX over the 15-year interval. Mean age was 73+/-10 years; 78% (199/255) were female. Of all PEX patients, 16% were placed on therapy at the time of initial diagnosis of PEX. In the remaining PEX patients, the probability of being placed on therapy was 44% at 15 years. Bilateral PEX was present in 25% at initial diagnosis and developed in another 29% by 15 years. Of those not placed on therapy, 16% (23/142) had IOP increase 5+ mm Hg during follow-up, with 11% (16/142) reaching 22 mm Hg or more. The strongest risk factors for converting to therapy were IOP at initial diagnosis of PEX and bilateral involvement. CONCLUSIONS: In a geographically defined population of PEX patients, 16% required treatment upon presentation. Of the remaining PEX patients, 44% received therapy over the next 15 years.

Prevalence of floppy eyelid syndrome in obstructive sleep apnea-hypopnea syndrome.

OBJECTIVES: To determine the prevalence of floppy eyelid syndrome (FES) in obstructive sleep apnea-hypopnea syndrome (OSAHS) and to develop a method to measure eyelid laxity. DESIGN: Masked cross-sectional (prevalence) study examining patients referred to the Mayo Sleep Disorders Center. PARTICIPANTS AND/OR CONTROLS: Fifty-nine subjects were examined before undergoing polysomnography. Forty-four subjects had OSAHS, and 15 did not have it. TESTING: Subjects underwent slit-lamp examination and eyelid laxity measurements, followed by polysomnography. MAIN OUTCOME MEASURES: Presence of FES as defined by subjectively easy eyelid eversion, tarsal papillary conjunctivitis, and lash ptosis; force required to displace the upper lid 5 mm, as measured by a strain gauge device; number of apnea or hypopnea episodes per hour (apnea-hypopnea index [AHI]); presence of OSAHS, as defined by an AHI of > or =5; and abnormalities on electrocardiography. RESULTS: One patient with OSAHS was found to have FES, yielding a prevalence of 2.3% (95% confidence interval [CI]: 0.1%-12.0%). One patient was referred to the Sleep Disorders Center due to a diagnosis of FES; if this patient were included, the prevalence would be 4.5% (95% CI: 0.5%-15.1%). Subjectively easy lid eversion was more common in OSAHS patients than in non-OSAHS patients. When adjusted for age and body mass index, there was a trend for association between subjectively easy lid eversion and OSAHS, but this did not reach statistical significance. Subjectively easy lid eversion was associated with AHI. Force required to displace the upper lid 5 mm was lower in lids with subjectively easy eversion, but was not associated with OSAHS or AHI. Intraclass correlation among 3 strain gauge measurements was good for both right (82%) and left (83%) lids. There were no statistically significant differences in frequency of electrocardiographic abnormalities among the various groups. CONCLUSIONS: The prevalence of FES among OSAHS patients is low. Patients with subjectively easy upper lid eversion are at risk for OSAHS. By recognizing the potential for OSAHS in these patients, the ophthalmologist may play an important role in initiating their evaluation and treatment.

The role of VEGF and IGF-1 in a hypercarbic oxygen-induced retinopathy rat model of ROP.

PURPOSE: We have previously described a severe form of oxygen-induced retinopathy (OIR) in the neonatal rat, analogous to human retinopathy of prematurity (ROP), where carbon dioxide is added to the inspired environment (hypercarbic OIR). We studied the time course of emergence and resolution of neovascularization (NV) in normocarbic OIR and hypercarbic OIR and the associated changes in VEGF and IGF-1 mRNA levels in hypercarbic OIR. METHODS: 550 newborn Sprague-Dawley rats were raised in 22 expanded litters of 25. Beginning at day 1 of life, rats were exposed to 7 daily cycles of hyperoxia (80% O2, 20.5 h) and hypoxia (10% O2, 0.5 h) with a gradual return to 80% O2 over 3 h. Inspired CO2 was maintained at 0.2% for 200 rats (normocarbic OIR) and 10% for 100 rats (hypercarbic OIR). Rats were sacrificed after a subsequent 5 day room air recovery period. An additional 250 rats raised in room air served as age matched controls. Retinae from left eyes were dissected and flatmounts were ADPase-stained. The presence and severity of NV was scored in a masked manner. Right eyes in hypercarbic OIR litters and room air controls were processed for analysis of VEGF and IGF-1 mRNA. RESULTS: In normocarbic OIR, NV started to emerge before room air recovery began at day 8. It was maximal at day 10 and resolved by day 20. In hypercarbic OIR, a similar pattern was seen, with emergence prior to day 8, peak at day 13 and resolution by day 20. In hypercarbic OIR, retinal VEGF mRNA was decreased at day 8 and increased at day 10 compared to room air controls, correlating with maximal NV. Retinal IGF-1 mRNA was not increased at any time in hypercarbic OIR compared to room air controls. CONCLUSIONS: Neovascularization resulting from normocarbic OIR or hypercarbic OIR occurs before room air recovery. Retinal VEGF mRNA was downregulated and subsequently upregulated prior to maximal NV in hypercarbic OIR. Neovascularization in the hypercarbic OIR model does not appear to be associated with increased retinal IGF-1 mRNA.

Estimated incidence of pseudoexfoliation syndrome and pseudoexfoliation glaucoma in Olmsted County, Minnesota.

PURPOSE: To determine the incidence of newly diagnosed pseudoexfoliation syndrome and pseudoexfoliation glaucoma in residents of Olmsted County, Minnesota from 1976 to 1991. MATERIALS AND METHODS: The database of the Rochester Epidemiology Project was used to identify all patients residing in Olmsted County who were newly diagnosed with pseudoexfoliation syndrome from 1976 to 1991. The criterion used to diagnose pseudoexfoliation syndrome was the presence of pseudoexfoliation material on 1 or more anterior segment structures. Criteria used to diagnose pseudoexfoliation glaucoma were diagnosis of pseudoexfoliation syndrome with evidence of glaucomatous changes or ocular hypertension receiving therapy. The overall age and sex-adjusted annual incidences of pseudoexfoliation syndrome and pseudoexfoliation glaucoma, adjusted to the 1990 US white population, were determined with differences across age and sex using Poisson regression. RESULTS: Pseudoexfoliation syndrome was diagnosed in 290 patients (mean age, 73 +/- 10 years). Two hundred twenty-one (76%) were female. The overall age and sex-adjusted annual incidence of pseudoexfoliation syndrome was 25.9 per 100,000. The age-adjusted incidence was higher in females than in males (32.7 vs 16.9 per 100,000; P<0.001). Pseudoexfoliation syndrome diagnoses increased with age, from 2.8 per 100,000 in persons 40 to 49 years to 205.7 per 100,000 in persons > or =80 years (P<0.001). Thirty-five patients were excluded from pseudoexfoliation glaucoma diagnosis. Of the remaining 255 patients, 113 (44%) were diagnosed with pseudoexfoliation glaucoma during the study period (mean age, 76 +/- 10 years), 84 (74%) of whom were female. The overall age- and sex-adjusted annual incidence of pseudoexfoliation glaucoma was 9.9 per 100,000. The age-adjusted incidence was higher in females than in males (11.7 vs 7.2 per 100,000; P < 0.001). Pseudoexfoliation glaucoma was increasingly diagnosed with age, rising from 0.6 per 100,000 in persons 40 to 49 years to 114.3 per 100,000 in persons > or =80 years, (P<0.001). CONCLUSIONS: In a defined population, the estimated overall age- and sex-adjusted annual incidence of pseudoexfoliation syndrome was 25.9 per 100,000 population, while the estimated overall age- and sex-adjusted annual incidence of pseudoexfoliation glaucoma was 9.9 per 100,000 population. The incidence of both diseases was higher in females and increased with advancing age.

Duration of acidosis and recovery determine preretinal neovascularization in the rat model of acidosis-induced retinopathy.

PURPOSE: Systemic acidosis is a risk factor for retinopathy of prematurity (ROP). The present study tested the hypotheses that: a) a short period of acidosis is sufficient to produce neovascularization and b) recovery from acidosis is not needed for the development of preretinal neovascularization. METHODS: Newborn Sprague-Dawley rats raised in 38 litters of 25 were randomly assigned within litters to 1, 3, or 6 days of acidosis, induced by twice daily gavage with NH4Cl (10 mM/kg) beginning on the second day of life. Recovery time ranged from 0 to 15 days. All animals were raised in room air. Animals were sacrificed and retinal vasculature was assessed for preretinal neovascularization and retinal vascular areas. RESULTS: Neovascularization occurred in up to 34% of rats exposed to 1 day of acidosis, 38% of rats exposed to 3 days of acidosis, and 55% of rats exposed to 6 days of acidosis. The incidence of neovascularization was maximal after 2 to 5 days of recovery regardless of the duration of NH4Cl exposure. However, recovery was not a requirement for the development of neovascularization. CONCLUSIONS: Periods of systemic acidosis as brief as 24 hours are associated with preretinal neovascularization in our newborn rat model of ROP using expanded litters. Systemic acidosis may damage the developing retinal vasculature and induce neovascularization, even without a period of recovery. A brief episode of systemic acidosis may be a risk factor for ROP in human neonates. Further attention should be directed to systemic acid-base balance in infants at risk for ROP.