Showing papers in "Archives of Ophthalmology in 2002"

The Ocular Hypertension Treatment Study: A Randomized Trial Determines That Topical Ocular Hypotensive Medication Delays or Prevents the Onset of Primary Open-Angle Glaucoma

Abstract: Background Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. Three to 6 million people in the United States are at increased risk for developing POAG because of elevated intraocular pressure (IOP), or ocular hypertension. There is no consensus on the efficacy of medical treatment in delaying or preventing the onset of POAG in individuals with elevated IOP. Therefore, we designed a randomized clinical trial, the Ocular Hypertension Treatment Study. Objective To determine the safety and efficacy of topical ocular hypotensive medication in delaying or preventing the onset of POAG. Methods A total of 1636 participants with no evidence of glaucomatous damage, aged 40 to 80 years, and with an IOP between 24 mm Hg and 32 mm Hg in one eye and between 21 mm Hg and 32 mm Hg in the other eye were randomized to either observation or treatment with commercially available topical ocular hypotensive medication. The goal in the medication group was to reduce the IOP by 20% or more and to reach an IOP of 24 mm Hg or less. Main Outcome Measures The primary outcome was the development of reproducible visual field abnormality or reproducible optic disc deterioration attributed to POAG. Abnormalities were determined by masked certified readers at the reading centers, and attribution to POAG was decided by the masked Endpoint Committee. Results During the course of the study, the mean ± SD reduction in IOP in the medication group was 22.5% ± 9.9%. The IOP declined by 4.0%± 11.6% in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group (hazard ratio, 0.40; 95% confidence interval, 0.27-0.59; P Conclusions Topical ocular hypotensive medication was effective in delaying or preventing the onset of POAG in individuals with elevated IOP. Although this does not imply that all patients with borderline or elevated IOP should receive medication, clinicians should consider initiating treatment for individuals with ocular hypertension who are at moderate or high risk for developing POAG.

Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial.

Abstract: Objective To provide the results of the Early Manifest Glaucoma Trial, which compared the effect of immediately lowering the intraocular pressure (IOP), vs no treatment or later treatment, on the progression of newly detected open-angle glaucoma. Design Randomized clinical trial. Participants Two hundred fifty-five patients aged 50 to 80 years (median, 68 years) with early glaucoma, visual field defects (median mean deviation, −4 dB), and a median IOP of 20 mm Hg, mainly identified through a population screening. Patients with an IOP greater than 30 mm Hg or advanced visual field loss were ineligible. Interventions Patients were randomized to either laser trabeculoplasty plus topical betaxolol hydrochloride (n = 129) or no initial treatment (n = 126). Study visits included Humphrey Full Threshold 30-2 visual field tests and tonometry every 3 months, and optic disc photography every 6 months. Decisions regarding treatment were made jointly with the patient when progression occurred and thereafter. Main Outcome Measures Glaucoma progression was defined by specific visual field and optic disc outcomes. Criteria for perimetric progression were computer based and defined as the same 3 or more test point locations showing significant deterioration from baseline in glaucoma change probability maps from 3 consecutive tests. Optic disc progression was determined by masked graders using flicker chronoscopy plus side-by-side photogradings. Results After a median follow-up period of 6 years (range, 51-102 months), retention was excellent, with only 6 patients lost to follow-up for reasons other than death. On average, treatment reduced the IOP by 5.1 mm Hg or 25%, a reduction maintained throughout follow-up. Progression was less frequent in the treatment group (58/129; 45%) than in controls (78/126; 62%) ( P =.007) and occurred significantly later in treated patients. Treatment effects were also evident when stratifying patients by median IOP, mean deviation, and age as well as exfoliation status. Although patients reported few systemic or ocular conditions, increases in clinical nuclear lens opacity gradings were associated with treatment ( P = .002). Conclusions The Early Manifest Glaucoma Trial is the first adequately powered randomized trial with an untreated control arm to evaluate the effects of IOP reduction in patients with open-angle glaucoma who have elevated and normal IOP. Its intent-to-treat analysis showed considerable beneficial effects of treatment that significantly delayed progression. Whereas progression varied across patient categories, treatment effects were present in both older and younger patients, high- and normal-tension glaucoma, and eyes with less and greater visual field loss.

The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma.

Abstract: Background The Ocular Hypertension Treatment Study (OHTS) has shown that topical ocular hypotensive medication is effective in delaying or preventing the onset of primary open-angle glaucoma (POAG) in individuals with elevated intraocular pressure (ocular hypertension) and no evidence of glaucomatous damage. Objective To describe baseline demographic and clinical factors that predict which participants in the OHTS developed POAG. Methods Baseline demographic and clinical data were collected prior to randomization except for corneal thickness measurements, which were performed during follow-up. Proportional hazards models were used to identify factors that predicted which participants in the OHTS developed POAG. Results In univariate analyses, baseline factors that predicted the development of POAG included older age, race (African American), sex (male), larger vertical cup-disc ratio, larger horizontal cup-disc ratio, higher intraocular pressure, greater Humphrey visual field pattern standard deviation, heart disease, and thinner central corneal measurement. In multivariate analyses, baseline factors that predicted the development of POAG included older age, larger vertical or horizontal cup-disc ratio, higher intraocular pressure, greater pattern standard deviation, and thinner central corneal measurement. Conclusions Baseline age, vertical and horizontal cup-disc ratio, pattern standard deviation, and intraocular pressure were good predictors for the onset of POAG in the OHTS. Central corneal thickness was found to be a powerful predictor for the development of POAG.

Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment.

Abstract: Objective To evaluate the safety and efficacy of intravitreal injections of an antigen-binding fragment of a recombinant humanized monoclonal antibody directed toward vascular endothelial growth factor (rhuFab VEGF) in a monkey model of choroidal neovascularization (CNV). Methods In phase 1 of the study, each animal received intravitreal injections, 500 µg per eye, of rhuFab VEGF in one eye (prevention eye), while the contralateral eye received rhuFab VEGF vehicle (control eye) at 2-week intervals. On day 21, laser photocoagulation was performed to induce CNV. In phase 2, the vehicle-treated eye was crossed over and both eyes received 500 µg of rhuFab VEGF beginning 21 days following laser-induced injury at days 42 and 56. The eyes were monitored by ophthalmic examinations, color photographs, and fluorescein angiography. Results rhuFab VEGF did not cause any ocular hemorrhages. All eyes treated with rhuFab VEGF developed acute anterior chamber inflammation within 24 hours of the first injection that resolved within 1 week, and this inflammation was less severe with subsequent injections. The incidence of CNV, defined angiographically, was significantly lower in the prevention eyes than the control eyes ( P P = .001). Conclusions Intravitreal rhuFab VEGF injections prevented formation of clinically significant CNV in cynomolgus monkeys and decreased leakage of already formed CNV with no significant toxic effects. Clinical Relevance This study provides the nonclinical proof of principle for ongoing clinical studies of intravitreally injected rhuFab VEGF in patients with neovascular age-related macular degeneration.

The Role of Apoptosis in Age-Related Macular Degeneration

Abstract: Objective To investigate apoptosis in human age-related macular degeneration (AMD). Methods Postmortem retinas with AMD and normal retinas were studied by terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) to identify dying cells, and by immunocytochemistry with cell-specific antibodies to identify rods and cones. Sections were also labeled for Fas, a cell surface receptor that triggers apoptosis in other cell types. The maculas with AMD had geographic atrophy (GA) or exudative AMD. Results Maculas with AMD had statistically significant increases in TUNEL-positive cells in the inner choroid, retinal pigment epithelium (RPE), photoreceptors, and inner nuclear layers compared with normal retinas. In eyes with GA, TUNEL-positive rod and RPE cell nuclei were present near edges of RPE atrophy. Photoreceptors in the maculas of eyes with AMD were strongly Fas-positive, while normal photoreceptors were only weakly labeled. Conclusions Evidence in this study suggests that in human AMD, RPE, photoreceptors, and inner nuclear layer cells die by apoptosis. Most TUNEL-positive RPE and photoreceptor cells were at edges of atrophy, correlating with clinically observed expansion of atrophic areas with vision loss in patients with GA. Increased Fas labeling in AMD photoreceptors indicates that the Fas/Fas ligand system may be involved in photoreceptor apoptosis. This information is essential for developing rational therapy for AMD.

A randomized trial of atropine vs patching for treatment of moderate amblyopia in children

Abstract: Results: Visual acuity in the amblyopic eye improved in both groups (improvement from baseline to 6 months was 3.16 lines in the patching group and 2.84 lines in the atropine group). Improvement was initially faster in the patching group, but after 6 months, the difference in visual acuity between treatment groups was small and clinically inconsequential (mean difference at 6 months, 0.034 logMAR units; 95% confidence interval, 0.0050.064 logMAR units). The 6-month acuity was 20/30 or better in the amblyopic eye and/or improved from baseline by 3 or more lines in 79% of the patching group and 74% of the atropine group. Both treatments were well tolerated, although atropine had a slightly higher degree of acceptability on a parental questionnaire. More patients in the atropine group than in the patching group had reduced acuity in the sound eye at 6 months, but this did not persist with further follow-up.

Anatomical outcomes of surgery for idiopathic macular hole as determined by optical coherence tomography

Abstract: Objectives To determine the rate of anatomical closure of idiopathic macular holes undergoing vitreous surgery with respect to preoperative horizontal diameter as determined by optical coherence tomography (OCT) and to correlate postoperative visual acuity, duration of symptoms, and late reopening with initial idiopathic macular hole diameter by OCT. Materials and Methods Forty eyes of 40 patients with an idiopathic macular hole were examined with OCT before and after vitreous surgery. All eyes were treated with pars plana vitrectomy, peeling of posterior cortical vitreous, and dilute perfluoropropane or sulfur hexafluoride gas. Face-down positioning was maintained for 7 to 14 days. Results Twenty-two (92%) of 24 eyes with a preoperative idiopathic macular hole diameter smaller than 400 µm measured by OCT attained anatomical closure following surgery. Anatomical closure was observed in 9 (56%) of 16 eyes with a macular hole diameter of 400 µm or larger measured by OCT ( P = .02). The median postoperative visual acuity improvement was 4 Snellen lines in the 31 eyes achieving anatomical closure and no change in the 9 eyes not achieving anatomical closure ( P P = .02) and duration of symptoms( P = .02) were factors predictive of anatomical closure of the macular hole postoperatively. Conclusions The postoperative closure of idiopathic macular holes following vitreous surgery was related to the preoperative macular hole diameter determined by OCT, with lesions smaller than 400 µm demonstrating higher success rates. A trend toward greater visual acuity improvement was demonstrated for idiopathic macular holes smaller than 400 µm. Late reopening was only seen in macular holes that were 400 µm or larger measured by OCT. Preoperative analysis and measurement of idiopathic macular holes with OCT may help delineate postoperative expectations for successful anatomical closure of the macular hole, visual acuity, and long-term closure.

How does visual impairment affect performance on tasks of everyday life? The SEE Project

Abstract: Objective To determine the association between performance on selected tasks of everyday life and impairment in visual acuity and contrast sensitivity. Methods Visual acuity and contrast sensitivity were obtained on a population-based sample of 2520 older African American and white subjects. Performance was assessed on mobility, daily activities with a strong visual component, and visually intensive tasks. Disability was defined as performance less than 1 SD below the mean. Receiver operating characteristic curve analyses were used to evaluate the sensitivity and specificity of thresholds in acuity and contrast loss for determining disability. Results Both visual acuity and contrast sensitivity loss were associated with decrements in function. The relationship of function to the vision measures was mostly linear, therefore, receiver operating characteristic curves were not helpful in identifying cutoff points for predicting disabilities. For mobility tasks, most persons were not disabled until they had significant acuity loss (logMAR visual acuity >1.0 or Conclusions Both contrast sensitivity and visual acuity loss contribute independently to deficits in performance on everyday tasks. Defining disability as deficits in performance relative to a population, it is possible to identify visual acuity and contrast loss where most are disabled. However, the cutoff points depend on the task, suggesting that defining disability using a single threshold for visual acuity or contrast sensitivity loss is arbitrary.

Goblet cell numbers and epithelial proliferation in the conjunctiva of patients with dry eye syndrome treated with cyclosporine.

Abstract: Objectives To compare conjunctival goblet cell numbers as well as epithelial turnover in patients with non–Sjogren syndrome–associated keratoconjunctivitis sicca (NSS-KCS) and those with SS-KCS before and after 6 months of treatment with topical cyclosporine A (CsA) ophthalmic emulsion. Methods Conjunctival biopsy specimens from 16 patients with NSS-KCS and 12 with SS-KCS were obtained at baseline and after 6 months' therapy with CsA or vehicle alone. Conjunctival biopsy specimens were also obtained from 11 normal subjects. Periodic acid–Schiff staining determined the number of goblet cells present. Immunofluorescence microscopy for Ki-67 localization was used to evaluate the number of actively cycling cells. Results Periodic acid–Schiff staining showed fewer goblet cells at baseline in both dry eye populations when compared with normal subjects ( P P P P Conclusions Treatment of dry eye syndrome for 6 months with topical CsA resulted in an increase in goblet cell numbers in patients with NSS-KCS and SS-KCS and a decrease in epithelial turnover in those with NSS-KCS. Reducing ocular surface inflammation might have an effect on the proliferative activity of the epithelium.

Incidence of Late-Onset Bleb-Related Complications Following Trabeculectomy With Mitomycin

Abstract: Objectives To determine the incidence of late-onset bleb-related complications following trabeculectomy with mitomycin and to report the management and outcome of bleb leaks following trabeculectomy with mitomycin. Methods A retrospective medical record review of all patients who underwent trabeculectomy with mitomycin from June 1, 1991, through April 30, 1998, at our institution was performed. The Kaplan-Meier survival method was used to estimate the probability of (1) endophthalmitis, (2) blebitis, (3) a bleb leak, and (4) the combined outcome (the first occurrence of a bleb leak, blebitis, or endophthalmitis). This survival analysis included only the first trabeculectomy in an eye, with at least 3 months of follow-up during the study period. A separate description of bleb leak management and outcome was performed. Results Two hundred thirty-nine eyes of 198 patients were included in the survival analysis. The average follow-up was 2.7 (range, 0.3-7.3) years. Twenty eyes(8%) from 19 patients experienced a bleb leak; the adjusted incidence was 3.2% per patient-year. Five eyes (2%) had an episode of blebitis. Eight eyes(3%) experienced an episode of endophthalmitis; the follow-up adjusted incidence(number of events per patient-year) was 1.3%. Twenty-seven eyes (11%) from 26 patients had at least 1 of the complications of a bleb leak, blebitis, or endophthalmitis; the adjusted incidence was 4.4% per patient-year. A Kaplan-Meier analysis estimated the 5-year probability of developing a bleb leak, blebitis, or endophthalmitis to be 17.9%, 6.3%, and 7.5%, respectively. Two hundred fifty-eight trabeculectomies in 242 eyes of 198 patients were included in the description of bleb leak management and outcome. Bleb leaks occurred in 22 eyes (9% of the 258 trabeculectomies). Seventeen eyes were successfully treated with office-based measures, and 4 ultimately underwent surgical bleb revision. One eye without infection continued to leak after 11 months of office-based therapy. Conclusions There is significant morbidity associated with a trabeculectomy with mitomycin. The incidence of a bleb leak or an infection continues at a fairly constant rate over time, such that at 5 years, up to 23% of all patients might develop one of these complications. An isolated bleb leak seems to be a relatively benign condition, as three quarters resolve with office-based methods.

Evidence-based screening criteria for retinopathy of prematurity: natural history data from the CRYO-ROP and LIGHT-ROP studies.

Abstract: Background The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity(CRYO-ROP) demonstrated the efficacy of treatment for threshold ROP and indicated the need for worldwide ROP screening. Previous guidelines for ROP screening have been largely based on clinical impression; we can now develop evidence-based screening recommendations. Objective To define the appropriate ages and retinal ophthalmoscopic signs that determine when to commence and conclude acute phase ROP screening. Design Analysis of data from 2 prospective randomized controlled trials: CRYO-ROP(January 1, 1986, to November 30, 1987) and Light Reduction in ROP (LIGHT-ROP)(July 1, 1995, to March 31, 1997). Setting Neonatal intensive care units in 23 study centers in the United States for CRYO-ROP and 3 centers for LIGHT-ROP. Patients Eyes were examined sequentially in 4099 infants with birth weight less than 1251 g (CRYO-ROP study) and in 361 infants with birth weight less than 1251 g and gestational age less than 31 weeks (LIGHT-ROP study). Results In 99% of infants, retinal conditions indicating a risk of poor outcome were not observed before 31 weeks' postmenstrual age or 4 weeks' chronologic age. Signs indicating that the risk of visual loss from ROP was minimal or had passed were the infant's attainment of 45 weeks' postmenstrual age without the development of prethreshold ROP or worse, progression of retinal vascularization into zone III without previous zone II ROP, and full vascularization. Conclusions The initial eye examination should be conducted by 31 weeks' postmenstrual age or 4 weeks' chronologic age, whichever is later. Acute phase ROP screening can be discontinued when any of the 3 signs is present, indicating that the risk of visual loss from ROP is minimal or passed.

Incident open-angle glaucoma and blood pressure.

Abstract: Background The risk of open-angle glaucoma (OAG) may be related to low blood pressure(BP) relative to intraocular pressure (IOP), ie, to low perfusion pressure(PP). Alternatively, systemic hypertension may increase OAG risk. Objective To clarify these possible relationships by evaluating hypertension and PP (where PP = BP − IOP) as risk factors for incident OAG in a black population. Design Population-based cohort study (85% participation); simple random sample of residents of Barbados, West Indies, aged 40 years and older. Participants Two thousand nine hundred eighty-nine black participants at risk; 67 developed OAG after 4 years (2.2% incidence). Main Outcome Measure Adjusted relative risk (RR) of OAG from logistic regression analyses. Results The 4-year risk increased markedly with baseline IOP. With an IOP less than or equal to 17 mm Hg, incidence was 0.7%, increasing to 18.3% with IOP greater than 25 mm Hg, for a 25-fold increase in RR. However, OAG developed throughout the IOP range and two thirds of incident cases had baseline IOP less than 25 mm Hg. Baseline hypertension was associated with a halving of the RR of OAG (RR, 0.49; 95% confidence interval [CI], 0.29-0.85); the RR also tended to decrease as systolic BP increased ( P = .07). Consistent with these findings, a lower baseline PP increased RR (systolic PP Conclusions As baseline IOP increased, the risk of OAG substantially increased. In contrast, persons with systemic hypertension at baseline had half the RR, suggesting that hypertension does not increase (and may decrease) the 4-year risk of OAG. Lower PP at baseline increased RR approximately 3-fold, a result consistent with the vascular hypothesis of OAG pathogenesis.

Effect of depression on vision function in age-related macular degeneration.

Abstract: Objectives To report the prevalence rate of depression in older patients with recent vision loss due to age-related macular degeneration (AMD) and to describe the effect of depression on self-reported vision function during 6 months. Methods Prospective cohort study of 51 older patients with recent-onset bilateral AMD attending the Retina Clinic of Wills Eye Hospital, Philadelphia, Pa. Main outcome measures included the Center for Epidemiological Studies Depression Scale, visual acuity, Functional Vision Screening Questionnaire, Chronic Disease Score, and Community Disability Scale. Results Seventeen patients (33%) were depressed at baseline and had worse visual acuity ( P = .04) and greater levels of vision-specific( P = .03) and general ( P = .002) physical disability than nondepressed patients. The correlations of Center for Epidemiological Studies Depression Scale score with visual acuity and visual-specific disability, however, were not significant after controlling for general physical disability. An increase in depressive symptoms over time predicted decline in self-reported vision function independent of changes in visual acuity or medical status ( P Conclusions The prevalence and disabling effects of depression in older patients with AMD are substantial. Recognizing that depression is a treatable disorder that exacerbates the effects of AMD will lead to improved outcomes. Innovative interventions to prevent or treat depression in specialty eye clinics are possible.

The Distribution of Mitochondrial Activity in Relation to Optic Nerve Structure

Abstract: Background The observation of a buildup of mitochondria at the level of the lamina cribrosa in the optic nerve head has traditionally been attributed to axoplasmic stasis. However, this region is also the transition zone for myelination, resulting in differing energy requirements. Objective To investigate the relationship between myelination and mitochondrial activity in optic nerve tissue. Methods Histological, histochemical, and immunocytochemical techniques were used to demonstrate the distribution of myelin, cytochrome- c oxidase activity, and laminar structure in human optic nerve tissue. A study of rabbit optic nerve and retina and unmyelinated human pituitary stalk was also performed. Cytochrome- c oxidase activity in the human optic nerve tissue was measured using microphotometry. Results There was a striking inverse relationship between myelination and mitochondrial distribution in all tissue studied. Statistical analysis of microphotometric data showed this distribution to be highly significant. Conclusion We caution against the previous inference of a process of axoplasmic stasis and suggest that, instead, the distribution of mitochondria reflects the functional requirement of different regions of the ganglion cell axon. Clinical Relevance Optic neuropathy is associated with several inherited disorders of mitochondria. We suggest that a fine balance exists between energy demand and tissue function in the optic nerve, which may explain why optic nerve pathological features are seen in those with mitochondrial disease.

Postenucleation Adjuvant Therapy in High-Risk Retinoblastoma

Abstract: Purpose: The main purpose of this study was to determine the efficacy of postenucleation adjuvant therapy in preventing metastasis in cases of high-risk retinoblastoma. Methods: This was a retrospective, nonrandomized comparative study. Of 1020 consecutive patients with retinoblastoma had were managed at a referral center between January 1974 and December 1999, 80 (8%) of those analyzed had unilateral sporadic cases that were treated by primary enucleation and that had high-risk characteristics for metastasis on histopathology reports (anterior chamber seeding, iris infiltration, ciliary body infiltration, massive choroidal infiltration, invasion of optic nerve lamina cribrosa, retrolaminar optic nerve invasion, invasion of optic nerve transection, scleral infiltration, and extrascleral extension). The main outcome measure was the development of metastasis at a minimum follow-up period of 12 months. Results: There were 44 male and 36 female patients, with age ranging from 1 day to 16 years (median, 33 months). A single histopathologic high-risk characteristic was present in 50 patients (62.5%). Thirty patients (37.5%) manifested 2 or more high-risk characteristics. Forty-six patients (58%) had received postenucleation adjuvant therapy (chemotherapy with or without orbital external beam radiotherapy). Adjuvant therapy was not administered in 34 patients (42%). Metastasis occurred in 10 patients (13%) at a median of 9 months (range, 6-57 months) following enucleation. Eight (80%) of those who developed metastasis had not received adjuvant therapy. A significant difference (P=.02) was found in the incidence of metastasis between the group that had received adjuvant therapy (4%; 2/46) and the group that had not (24%; 8/34). The beneficial effect of adjuvant therapy was statistically significant in subgroups of patients with massive choroidal infiltration (P=.04) or retrolaminar optic nerve invasion (P=.04). There were no adjuvant therapy–related serious systemic complications. Conclusion: Postenucleation adjuvant therapy is safe and effective in significantly reducing the occurrence of metastasis in patients with retinoblastoma manifesting histopathologic high-risk characteristics. Arch Ophthalmol. 2002;120:923-931

The Association of Cataract and Cataract Surgery With the Long-Term Incidence of Age-Related Maculopathy: The Beaver Dam Eye Study

Abstract: Objective To examine the association between cataract and cataract surgery and the 10-year incidence of age-related maculopathy (ARM). Methods A population-based cohort study of persons aged 43 to 86 years at baseline, living in Beaver Dam, Wis, of whom 3684 participated in a 5-year and 2764 in a 10-year follow-up. We used standardized protocols for physical examination, blood collection, health history, slitlamp and retroillumination photography of the lenses to determine the presence of cataract, and stereoscopic color fundus photography to determine the presence of ARM. We used the Kaplan-Meier(product-limit) survival approach and discrete linear logistic regression in analyses. Main Outcome Measures The risk ratios (RRs) of persons with cataract or cataract surgery at baseline. Results While controlling for age, sex, systolic blood pressure, history of heavy drinking and smoking, and vitamin use, cataract at baseline was associated with incidence of early ARM (RR, 1.30; 95% confidence interval [CI], 1.04-1.63), soft indistinct drusen (RR, 1.38; 95% CI, 1.08-1.75), increased retinal pigment(RR, 1.38; 95% CI, 1.07-1.79), and progression of ARM (RR, 1.37; 95% CI, 1.06-1.77). We found no association with the incidence of late ARM. In contrast, cataract surgery before baseline was associated with incidence of late ARM (RR, 3.81; 95% CI, 1.89-7.69), increased retinal pigment (RR, 1.89; 95% CI, 1.18-3.03), retinal pigment epithelial depigmentation (RR, 1.95; 95% CI, 1.17-3.25), pure geographic atrophy (RR, 3.18; 95% CI, 1.33-7.60), exudative macular degeneration(RR, 4.31; 95% CI, 1.71-10.9), and progression of ARM (RR, 1.97; 95% CI, 1.29-3.02), but not with the incidence of early ARM. Conclusions These findings indicate an association of cataract with subsequent risk for early ARM. Cataract surgery increased the risk for late ARM.

Verteporfin therapy for subfoveal choroidal neovascularization in age-related macular degeneration: three-year results of an open-label extension of 2 randomized clinical trials--TAP Report no. 5.

Abstract: To report vision and safety outcomes from an extension of a 2-year investigation evaluating verteporfin photodynamic therapy in patients with age-related macular degeneration with subfoveal choroidal neovascularization (CNV).

One-year, randomized study comparing bimatoprost and timolol in glaucoma and ocular hypertension.

Abstract: Objective To compare bimatoprost with timolol maleate in patients with glaucoma or ocular hypertension. Methods In 2 identical, multicenter, randomized, double-masked, 1-year clinical trials, patients were treated with 0.03% bimatoprost once daily (QD) (n = 474), 0.03% bimatoprost twice daily (BID) (n = 483), or 0.5% timolol maleate BID (n = 241). Main Outcome Measures Diurnal intraocular pressure (IOP) at 8 AM, 10 AM, and 4 PM and safety variables (IOP was also measured at 8 PM at selected sites). Results Bimatoprost QD provided significantly lower mean IOP than timolol at every time of the day at each study visit ( P P P P Conclusions Bimatoprost QD provides sustained IOP lowering superior to timolol or bimatoprost BID and achieves low target IOPs in significantly more patients.

Association Between Sleep Apnea Syndrome and Nonarteritic Anterior Ischemic Optic Neuropathy

Abstract: Objective To determine if patients with nonarteritic ischemic optic neuropathy(NAION) have sleep apnea syndrome (SAS), an entity characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption. Methods We recruited 17 patients with NAION and 17 age- and sex-matched controls from patients referred for treatment because of suspected restless legs syndrome. We performed overnight polysomnography and determined the respiratory disturbance index during night sleep, a value used to diagnose and grade SAS. We compared the proportions of patients with SAS among patients with NAION and matched controls using the χ 2 test. Additionally, we compared the proportions of patients with SAS among patients with NAION and a large SAS prevalence study using the binomial test. Results Twelve (71%) of 17 patients with NAION had SAS. According to the respiratory disturbance index, 4 patients (24%) had mild, 4 patients (24%) had moderate, and 4 patients (24%) had severe SAS. Only 3 (18%) of 17 controls had SAS ( P = .005). In the 45- to 64-year age group, 4 (50%) of 8 patients with NAION had SAS; 51 (11.9%) of 430 of the random sample in the prevalence study had SAS ( P = .005). In the group older than 64 years, 8 (89%) of 9 patients with NAION had SAS; 18 (24%) of 75 of the random sample in the prevalence study had SAS ( P Conclusions We found a high prevalence of SAS in patients with NAION, which supports previous case reports suggesting that such an association exists. This association may explain why approximately 75% of all patients with NAION discover visual loss on first awakening or when they first use vision critically after sleeping. Our findings indicate that SAS may play an important role in the pathogenesis of NAION.

Corneal optical aberrations and retinal image quality in patients in whom monofocal intraocular lenses were implanted.

Abstract: Objectives: To compare retinal image quality and optical corneal aberrations in patients in whom monofocal polymethyl methacrylate intraocular lenses (IOLs) were implanted with those in healthy subjects of a similar older age (60-70 years old) and to use the results to suggest improved optical designs of IOLs to maximize retinal image quality. Methods: A double-pass apparatus was used to measure retinal image quality for 3-, 4-, and 6-mm pupil diameters. Corneal aberrations for a 4-mm pupil were calculated by a ray-tracing technique from the elevations provided by cornealtopography.Twogroupsof20subjectsofasimilarolder age were studied: in one group, polymethyl methacrylate monofocal IOLs were implanted; and in a second group, healthy subjects were used as a reference. Results: The average retinal image quality was similar in older healthy patients and in patients in whom IOLs were implanted, with both groups having a significantly worse image quality than healthy younger subjects (aged 20-30 years). Both groups were more tolerant to defocus than younger subjects. Conclusions: The average retinal image quality of patients in whom IOLs were implanted was worse than that of healthy younger subjects despite the good optical quality of isolated IOLs. This apparent paradox can be understood by the nature of the aberration coupling in the eyes that undergo implantation. The ideal substitute for the natural lens is not an IOL with the best-isolated optical performance, but rather one designed to compensate for the aberrations of the cornea—a design somehow inspired by the crystalline lens of younger subjects.

Quality of Life With Visual Acuity Loss From Diabetic Retinopathy and Age-Related Macular Degeneration

Abstract: Objective To compare the quality of life in patients with visual acuity loss occurring secondary to diabetic retinopathy with visual acuity loss occurring secondary to age-related macular degeneration (ARMD). Methods Consecutive patients with diabetic retinopathy and ARMD were evaluated using the time trade-off method of utility value analysis. Both groups were stratified according to the degree of visual acuity loss in the better-seeing eye (group 1: 20/20-20/25, group 2: 20/30-20/40, group 3: 20/50-20/100, group 4: ≤20/200). Utility values obtained from the patients, once stratified for visual acuity group, were compared with use of the t test and the Mann-Whitney U test. In addition, a 2-way analysis of variance was performed to control for potential confounding variables. Results No difference was found between the utility value means of the diabetic retinopathy (n = 333) and ARMD (n = 246) subgroups stratified according to visual acuity levels: group 1, P = .54; group 2, P = .96; group 3, P = .09; and group 4, P = .32. A 2-way analysis of variance demonstrated that, among the variables of ocular disease, sex, age, and visual acuity in the better-seeing eye, only visual acuity was significantly associated with utility values ( P = .003). Conclusions At similar levels of visual acuity loss, that associated with diabetic retinopathy causes a similar reduction in quality of life to that associated with ARMD. This information has important implications for use in cost-utility analyses of ophthalmic interventions.

Glaucoma in zulus: a population-based cross-sectional survey in a rural district in south africa

Abstract: Objectives To determine the prevalence and the main types of glaucoma in a representative adult population in rural Zululand, and to describe the distribution of glaucoma-related variables in healthy subjects and those with glaucoma. Design A population-based, cross-sectional study. Setting Hlabisa district, Northern KwaZulu-Natal Province, South Africa. Participants Resident individuals of Zulu ethnic origin, 40 years or older. Main Outcome Measures Glaucoma was diagnosed by means of strict objective criteria, based on binocular indirect ophthalmoscopic optic disc appearances validated by results of disc photography and threshold visual field testing. Results From an eligible sample of 1115 subjects, 1005 (90.1%) were examined in the survey. The adjusted prevalence of glaucoma of all types was 4.5%, and primary open-angle glaucoma accounted for 2.7%. Secondary glaucoma occurred with an adjusted prevalence of 1.7%, of which the principal contributors were exfoliative and aphakic glaucoma. The prevalence of primary angle-closure glaucoma was low. Normal tension (intraocular pressure, ≤21 mm Hg) was measured in 16 (57.1%) of 28 cases of primary open-angle glaucoma. Age- and sex-adjusted prevalence of bilateral blindness was 3.2%, which was exclusively due to glaucoma in 9 (22.0%) of 41 cases. Conclusions Primary and secondary glaucoma constitute a significant public health problem in rural Zululand. The prevalence and types of glaucoma vary among different black populations.

Near-work activity, night-lights, and myopia in the Singapore-China study.

Abstract: Objective To investigate the relationship among near-work activity, night-lights, and myopia in schoolchildren in Singapore and Xiamen, China. Methods The refractive error and ocular dimensions of 957 Chinese schoolchildren aged 7 to 9 years in Singapore and Xiamen, China, were determined using cycloplegic autorefraction and A-scan ultrasound biometry. Information on near-work activity(number of books read per week, reading in hours per day) and night-light use before age 2 years was obtained. Results The prevalence rate of myopia was 36.7% (95% confidence interval [CI], 33.0%-40.3%) in Singapore and 18.5% (95% CI, 14.0%-23.1%) in Xiamen, China. The crude odds ratio (OR) of higher myopia (at least –3.0 diopters) for children who read more than 2 books per week was 3.50 (95% CI, 2.15-5.70). In a multivariate logistic regression model, the OR of higher myopia for children who read more was 2.81 (95% CI, 1.69-4.69), adjusted for age, night-light use, parental myopia, and country, whereas there was no association between night-light use before age 2 years and higher myopia (OR, 1.54; 95% CI, 0.92-2.58), after controlling for age, books read per week, parental myopia, and country. Main Outcome Measures The ORs of higher myopia for children who read more and children who are exposed to night-lights before age 2 years. Conclusions Reading (number of books per week) may be associated with higher myopia in Chinese schoolchildren. However, night-light use does not seem to be related to higher myopia.

Verteporfin therapy of subfoveal choroidal neovascularization in patients with age-related macular degeneration: additional information regarding baseline lesion composition's impact on vision outcomes-TAP report No. 3.

Abstract: To explore how baseline lesion composition influenced vision outcomes in patients with age-related macular degeneration (AMD) undergoing photodynamic therapy with verteporfin (Visudyne) for subfoveal choroidal neovascularization (CNV) in the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy Investigation.

Correlation of increased vascular endothelial growth factor with neovascularization and permeability in ischemic central vein occlusion.

Abstract: Objective To establish a role for vascular endothelial growth factor (VEGF) during the onset and clinical course of neovascularization of the iris (NVI) in ischemic central retinal vein occlusion. Methods Sixteen patients with ischemic central retinal vein occlusion were followed up for 12 months by clinical examination, retinal and iris angiography, and serial anterior chamber sampling of aqueous humor. Aqueous VEGF level was determined by enzyme-linked immunoassay, and permeability changes were estimated by capillary zone electrophoretic assessment of aqueous albumin. Results A correlation was found between aqueous VEGF concentrations and the onset, persistence, and regression of NVI; extent of retinal capillary nonperfusion; and vascular permeability. The NVI occurred when aqueous VEGF concentrations were 849 to 1569 pg/mL and regressed fully when they fell below 550 pg/mL. Aqueous concentrations of serum albumin, a marker of increased permeability, correlated with increased VEGF. Placental growth factor was found at low levels only when VEGF levels exceeded 330 pg/mL. The NVI remained VEGF-dependent during the course of the disease, regressing only if VEGF concentrations were reduced after laser ablation of hypoxic retina. Conclusions The close temporal correlation between aqueous VEGF levels and the course of neovascularization and permeability in human ischemic central retinal vein occlusion indicates that increased aqueous VEGF level may predict the need for treatment, and that anti-VEGF therapy at an early stage of ischemic central retinal vein occlusion may be therapeutically beneficial.

Smoking and the 5-year incidence of age-related maculopathy: the Blue Mountains Eye Study.

Abstract: Objective To assess the relationship between baseline smoking and the 5-year incidence of late and early age-related maculopathy (ARM) in an older population cohort. Methods The Blue Mountains Eye Study examined 3654 participants aged 49 years or older during 1992 to 1994 and then 2335 survivors (75.1%) after 5 years. Retinal photographs were graded using the Wisconsin Age-Related Maculopathy Grading System. Those with any ARM lesions at either examination were regraded in detail using a side-by-side method similar to that developed for the Beaver Dam Eye Study. We also used similar definitions for incident ARM lesions. Smoking status was recorded at interview. Results Age-standardized incidence rates for any late ARM lesions were 3.1%, 1.2%, and 1.4%, respectively, among baseline current, past, or never smokers. Corresponding age-standardized incidence rates for early ARM were 10.6%, 8.2%, and 9.3%, respectively. The mean age for cases with incident late ARM was 67 years for baseline current smokers, 73 years for past smokers, and 77 years for those who had never smoked (P= .02). After adjusting for age, current smokers, compared with never smokers, had an increased risk of incident geographic atrophy (age-adjusted relative risk [RR], 3.6; 95% confidence interval [CI], 1.1-11.3) and any late ARM lesions (RR, 2.5; 95% CI, 1.0-6.2). Current smokers had an increased risk of incident retinal pigmentary abnormalities (RR, 1.7; 95% CI, 1.1-2.7), with the risk higher in men (RR, 2.8; 95% CI, 1.4-5.6). Outcome Measures Five-year incidence of early ARM, late ARM, and ARM lesions. Conclusions In this cohort, persons who were current smokers had an increased risk of 5-year incident late ARM lesions and retinal pigmentary abnormalities. Current smokers developed late ARM at a significantly earlier age than never or past smokers.

Evidence-based estimates of outcome in patients irradiated for intraocular melanoma

Abstract: Background Melanoma of the eye is the only potentially fatal ocular malignancy in adults. Until radiation therapy gained wide acceptance in the 1980s, enucleation was the standard treatment for the tumor. Long-term results after proton beam irradiation are now available. Methods We developed risk score equations to estimate probabilities of the 4 principal treatment outcomes—local tumor recurrence, death from metastasis, retention of the treated eye, and vision loss—based on an analysis of 2069 patients treated with proton beam radiation for intraocular melanoma between July 10, 1975, and December 31, 1997. Median follow-up in surviving patients was 9.4 years. Results Tumor regrowth occurred in 60 patients, and 95% of tumors (95% confidence interval, 93%-96%) were controlled locally at 15 years. Risk scores were developed for the other 3 outcomes studied. Overall, the treated eye was retained by 84% of patients (95% confidence interval, 80%-87%) at 15 years. The probabilities for vision loss (visual acuity worse than 20/200) ranged from 100% to 20% at 10 years and for death from tumor metastases from 95% to 35% at 15 years, depending on the risk group. Conclusions High-dose radiation treatment was highly effective in achieving local control of intraocular melanomas. In most cases, the eye was salvaged, and functional vision was retained in many patients. The mortality rate was high in an identifiable subset of patients who may benefit from adjuvant therapies directed at microscopic liver metastases.

Trypan Blue Staining of Epiretinal Membranes in Proliferative Vitreoretinopathy

Abstract: Objective To determine whether trypan blue staining facilitates epiretinal membrane(ERM) removal in proliferative vitreoretinopathy. Methods In 10 patients undergoing vitrectomy for proliferative vitreoretinopathy, ERM peeling was performed without staining the tissue, until no additional ERMs were clearly visible. Then, after a fluid-air exchange, 0.06% trypan blue solution was applied onto the retinal surface. After 1 minute, all excess dye was removed and, after an air-fluid exchange, ERM peeling was completed. Excised ERM specimens were analyzed by transmission electron microscopy. Main Outcome Measures For each patient, the efficacy of trypan blue staining of ERMs during surgery was scored. Results In all patients, intraoperative staining of ERMs with trypan blue was found to be a useful adjunct, since the dye consistently improved direct visualization and delineation of ERMs and facilitated ERM removal. A clear contrast was created between the stained ERMs and the nonstaining, underlying retina. Electron microscopy showed that only ERM tissue was removed. No adverse reactions related to the use of the dye were observed up to 3 months after surgery. Conclusions Trypan blue may be an important new tool in the surgical management of proliferative vitreoretinopathy, since it may allow a more complete and safer ERM removal.