Deep learning based retinal OCT segmentation.

We look at the recent application of deep learning (DL) methods in automated fine-grained segmentation of spectral domain optical coherence tomography (OCT) images of the retina. We describe a new method combining fully convolutional networks (FCN) with Gaussian Processes for post processing. We report performance comparisons between the proposed approach, human clinicians, and other machine learning (ML) such as graph based approaches. The approach is demonstrated on an OCT dataset consisting of mild non-proliferative diabetic retinopathy from the University of Miami. The method is shown to have performance on par with humans, also compares favorably with the other ML methods, and appears to have as small or smaller mean unsigned error (equal to 1.06), versus errors ranging from 1.17 to 1.81 for other methods, and compared with human error of 1.10.

Manifest refraction versus autorefraction for patients with subfoveal choroidal neovascularization.

PURPOSE: To compare the results from manifest refraction using trial lenses and a standard visual acuity protocol to results from autorefraction for obtaining refractive error and best corrected visual acuity in patients enrolled in a randomized clinical trial. METHODS: During a 4-month period, 29 patients with subfoveal choroidal neovascularization (CNV), who were enrolled in the Submacular Surgery Trials (SSTs) Pilot Study at the Wilmer Ophthalmological Institute, gave verbal consent to participate in this study. Best corrected visual acuity was obtained using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts and standardized room lighting after performance of manifest refraction, according to the SST protocol, and autorefraction. Refractive error (spherical equivalent) and visual acuity scores were obtained in both eyes of all patients. RESULTS: On average, manifest refraction gave a spherical equivalent that was 1.04 D more plus than autorefraction (95% limits of agreement = 0.74, 1.34). On average, the visual acuity score was 1.5 letters better after manifest refraction than after autorefraction (95% limits of agreement = 0, 3.0). The comparison of the two methods of refraction was subdivided according to visual acuity level and eye disease (age-related macular degeneration or ocular histoplasmosis syndrome). CONCLUSIONS: Despite large differences in spherical equivalent between manifest refraction and autorefraction, the visual acuity scores were close (mean difference, 1.5 letters). Other studies comparing subjective refraction and autorefraction have shown similar results. Autorefraction in patients with subfoveal CNV may be a satisfactory alternative to manifest refraction in clinical trials and field studies in which best corrected visual acuity is of interest.

Measuring geographic atrophy in advanced age-related macular degeneration.

PURPOSE: To present a method developed for measuring areas of geographic atrophy (GA) in advanced age-related macular degeneration, METHODS: A microfilm reader projected the 30 degrees fundus photograph of the macula. Retinal landmarks, atrophic areas, and spared areas within the atrophy were traced, without access to drawings of other years. The total atrophic area was calculated, as was the atrophy within a four-disc-area circle entered on the estimated foveal center. The configuration of the atrophy was documented. RESULTS: Avoidable sources of discrepancy included variability in peripapillary atrophy seen on the photograph, and variability seen in the extent of the field. Reproducibility studies found a median absolute difference of 0.19 Macular Photocoagulation Study disc areas (DA) in total atrophy between repeat drawings, with 75% of repeat drawings having a difference of less than 0.33 DA. For central atrophy measures, there was a median difference of 0.08 DA, with 75% of pairs having a difference of less than 0.18 DA. Features making the definition of borders of GA difficult include the presence of drusen and pigmentary alteration, a fundus in which choroidal vessels are easily visible, and variation in the appearance of GA within a single area of atrophy. CONCLUSIONS: This method provides a reliable means of measuring the size of atrophic areas in GA and will be useful for measuring longitudinal change. It may be difficult to determine whether central spared areas are present, and correlation with visual acuity and macular perimetry may be helpful.

Cortical lenticular opacification: distribution and location in a longitudinal study.

PURPOSE: To examine the distribution of cortical opacification of the lens by lens quadrant in a longitudinal study. METHODS: In 1990, a follow-up assessment of a cohort of Chesapeake Bay watermen, initially studied in 1985, was performed. Four hundred thirty-seven subjects (834 eyes) had gradable cortical photographs for at least one eye in both 1985 and 1990. Cortical photographs were graded by both estimating total area and determining the quadrant with the greatest degree of cortical opacification. RESULTS: The prevalence and severity of cortical opacification increased with age with a high degree of concordance (84%) between eyes. For the 47 eyes with cortical opacification > or = 1/8 at baseline, the principal locations of opacification were: inferonasal 63.8%, inferotemporal 17.0%, superonasal 6.4%, and superotemporal 12.8% (P < 0.001, compared with equal distribution by quadrant). Five-year development of new cortical opacification and five-year progression of existing cortical opacification showed even greater preferential occurrence in the inferonasal quadrant of the lens. CONCLUSIONS: In this population, the inferonasal quadrant of the lens is the principal site of cortical opacification in both cross-sectional and longitudinal assessment. This finding is consistent with the hypothesis that sunlight exposure is a significant risk factor for cortical opacification.

Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials-tap report 2.

OBJECTIVE: To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, Ga) in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD). DESIGN: Two multicenter, double-masked, placebo-controlled, randomized clinical trials. SETTING: Twenty-two ophthalmology practices in Europe and North America. PARTICIPANTS: Patients with subfoveal CNV lesions caused by AMD with greatest linear dimension on the retina measuring 5400 micrometer or less, with evidence of classic CNV and best-corrected visual acuity (approximate Snellen equivalent) between 20/40 and 20/200. METHODS: The methods were similar to those described in our 1-year results, with follow-up examinations beyond 1 year continuing every 3 months (except for Photograph Reading Center evaluations, which occurred only at month 18 and month 24 examinations). During the second year, the same regimen (with verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV. The primary outcome was the proportion of eyes with fewer than 15 letters (approximately 3 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis. The last observation was carried forward to impute for any missing data. RESULTS: Three hundred fifty-one (87%) of 402 patients in the verteporfin group compared with 178 (86%) of 207 patients in the placebo group completed the month 24 examination. Beneficial outcomes with respect to visual acuity and contrast sensitivity noted at the month 12 examination in verteporfin-treated patients were sustained through the month 24 examination. At the month 24 examination for the primary outcome, 213 (53%) of 402 verteporfin-treated patients compared with 78 (38%) of 207 placebo-treated patients lost fewer than 15 letters (P<.001). In subgroup analyses for predominantly classic lesions (in which the area of classic CNV makes up at least 50% of the area of the entire lesion) at baseline, 94 (59%) of 159 verteporfin-treated patients compared with 26 (31%) of 83 placebo-treated patients lost fewer than 15 letters at the month 24 examination (P<.001). For minimally classic lesions (in which the area of classic CNV makes up <50% but >0% of the area of the entire lesion) at baseline, no statistically significant differences in visual acuity were noted. Few additional photosensitivity adverse reactions and injection site adverse events were associated with verteporfin therapy in the second year of follow-up. CONCLUSIONS: The visual acuity benefits of verteporfin therapy for AMD patients with predominantly classic CNV subfoveal lesions are safely sustained for 2 years, providing more compelling evidence to use verteporfin therapy for these cases. For AMD patients with subfoveal lesions that are minimally classic, there is insufficient evidence to warrant routine use of verteporfin therapy.

Clinical characteristics of choroidal neovascular membranes.

Eighty-three choroidal neovascular membranes (CNVMs) associated with pathologic entities other than age-related macular degeneration (study group) were compared with 64 CNVMs associated with macular degeneration (comparison group). Nine CNVMs (11%) in the study group, compared with 28 CNVMs (44%) in the comparison group, were occult membranes. Of the remaining well-defined CNVMs, 16 (22%) in the study group, compared with 21 (58%) in the comparison group, were subfoveal. Of the well-defined subfoveal membranes, four (25%) in the study group, compared with 17 (81%) in the control group, were large (greater than 1500 micron in size). All large subfoveal membranes occurred in patients over 55 years of age. Thus, in this study the majority of CNVMs associated with pathologic entities other than age-related macular degeneration were well defined and not subfoveal at initial presentation. The majority of CNVMs associated with macular degeneration were occult or subfoveal. Membranes in patients over 55 years of age, regardless of cause, were commonly found to be occult or subfoveal at presentation.

Sudden visual loss associated with sexual activity.

OBJECTIVE: To characterize the ocular fundus findings of patients who suffered sudden visual loss associated with sexual activity. DESIGN: Case series. SETTING: Outpatient ophthalmic practice. PATIENTS: Six patients presented with a precipitous decrease in vision in one eye with no apparent predisposing factors. After obtaining a careful history, each patient revealed that he or she had been engaging in rigorous sexual activity immediately before experiencing the visual loss. INTERVENTION: Five of the six patients were followed up without intervention. One patient required prophylactic laser photocoagulation of a retinal tear to decrease the risk of retinal detachment. RESULTS: Six patients aged 24 to 53 years suffered sudden loss of vision secondary to intraretinal, preretinal, or vitreous hemorrhaging. Visual acuity in the affected eyes ranged from a mild decrease (20/40) to profound visual loss (counting fingers at 6 in). Five of the six patients were followed up for at least 1 month and showed spontaneous improvement in vision as the blood cleared. Those who returned for long-term follow-up enjoyed complete visual recovery without any sequelae. CONCLUSIONS: Sudden debilitating visual loss may occur during sexual activity from the rupture of retinal blood vessels in the macular region or from the development of vitreous bleeding from an induced retinal tear. The long-term prognosis after such hemorrhaging appears to be excellent, with good visual recovery occurring as the blood resorbs spontaneously.

Loculated fluid. A previously undescribed fluorescein angiographic finding in choroidal neovascularization associated with macular degeneration. Macular Photocoagulation Study Reading Center.

The Foveal Photocoagulation Study, a component of the Macular Photocoagulation Study, is designed to evaluate whether laser treatment can reduce the risk of severe visual loss in eyes with well-defined choroidal neovascular membranes associated with macular degeneration that extend through the foveal center. On one third of the 554 baseline angiograms of study patients enrolled in and whose eyes were graded in the study as of January 31, 1990, the Reading Center staff has noted an unusual pattern of hyperfluorescence in the late-transit frames that has not been described previously. This pattern, which we call "loculated fluid," consists of a well-demarcated area of hyperfluorescence that appears to represent pooling of fluorescein in a compartmentalized space anterior to the choroidal neovascular leakage. Although the loculated fluid may conform to a pattern of typical cystoid macular edema, it can also pool within an area deep to the sensory retina in a shape that does not bear any resemblance to cystoid macular edema. This pattern is important to recognize because it (1) should not be confused with the angiographic pattern or extent of choroidal neovascularization and (2) should be differentiated from a serous detachment or tear of the retinal pigment epithelium.

Natural course of poorly defined choroidal neovascularization associated with macular degeneration.

We obtained follow-up data on 84 eyes with age-related macular degeneration and poorly defined angiographic leakage presumed to represent choroidal neovascularization. A poorly defined neovascular membrane was presumed to be present when subsensory retinal fluid was present in association with choroidal leakage on fluorescein angiography and in which the extent of leakage was not well defined. Among the 84 eyes, the average initial visual acuity was 20/80. In 75 (89%) of 84 eyes, the leakage involved the foveal center at initial presentation. At follow-up (average, 28 months; range, six to 53 months), the average visual acuity was 20/250; the final acuity declined at least three but less than six lines in 18 eyes (21%) and six or more lines in 35 eyes (42%). There was a statistically significant difference in the percentage of eyes that developed moderate or severe visual loss among eyes that progressed to disciform scarring compared with eyes that continued to manifest poorly defined leakage without evidence of scarring. Given that most severe visual loss associated with macular degeneration can be attributed to consequences of neovascular membranes and that many membranes associated with age-related macular degeneration are poorly defined, our study results support the possibility that poorly defined neovascular membranes represent a major cause of severe visual loss among the elderly in the United States.

Retinal pigment epithelial tears through the fovea with preservation of good visual acuity.

We describe two patients with spontaneous retinal pigment epithelial tears through the fovea who have maintained at least 20/40 visual acuity for 1 year and 3 years following the rip. Both patients had long-standing serous detachments of the retinal pigment epithelium associated with age-related macular degeneration prior to the development of the tear. Each tear was at least five disc areas in size and centered on the fovea. Foveal fixation was documented despite the presumed absence of pigment epithelium. This observation suggests either that there may be remaining or redundant pigment epithelium or that pigment epithelium directly beneath the central macula is not required for maintenance of 20/40 visual acuity.

Detecting recurrent choroidal neovascularization. Comparison of clinical examination with and without fluorescein angiography.

OBJECTIVE/DESIGN: To evaluate prospectively the ability of three retina specialists to detect recurrent choroidal neovascularization (CNV) after clinical examination alone and then with fluorescein angiography at 3 and 6 weeks and at 3, 6, 9, and 12 months after laser photocoagulation. SETTING: Single tertiary retinal referral center. PATIENTS: All patients who had laser treatment for CNV within 14 months of their study visit. One hundred thirty-seven eyes of 134 patients were evaluated during 401 visits. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value, and negative predictive value of clinical examination with biomicroscopy to detect recurrent CNV when defined as leakage on the periphery of the laser-treated area on the fluorescein angiogram. RESULTS: Ninety-seven definite or probable recurrences in 56 eyes were identified on the fluorescein angiogram. Clinical examination had a sensitivity of 59%, specificity of 94%, positive predictive value of 76%, and negative predictive value of 88%. These figures varied somewhat by underlying cause, age, time since treatment, and lesion location. Using either a reported or measured loss of vision with the results of biomicroscopy as an indication of recurrence increased the sensitivity to 77% but reduced the specificity to 81%. CONCLUSIONS: Clinical examination probably cannot replace fluorescein angiography in detecting all recurrent CNV after laser treatment. However, for follow-up visits in which recurrent CNV was not suspected on biomicroscopy, definite or questionable recurrent CNV was identified on the fluorescein angiogram only 12% of the time, while the absence of recurrent CNV using this method was confirmed 88% of the time.

The long-term effects of visible light on the eye.

The relationship between exposure to sunlight and senile cataract, age-related macular degeneration, pterygium, and climatic droplet keratopathy was examined in 838 watermen who work on the Chesapeake Bay. The presence and severity of lenticular, corneal, and macular changes were assessed by either clinical examination or from stereo macular photographs. From detailed exposure histories, ocular exposure was estimated for three bands of visible radiation-violet (400 to 450 nm), blue (400 to 500 nm), or all visible (400 to 700 nm)-as well as for UV-A (320 to 340 nm) and UV-B (290 to 320 nm). The results with each band of visible radiation were similar. Neither cortical nor nuclear cataract was associated with ocular exposure to blue or all visible radiation, but pterygium and climatic droplet keratopathy were more common with higher exposures. Compared with age-matched controls, patients with advanced age-related macular degeneration (geographic atrophy or disciform scarring) had significantly higher exposure to blue or visible light over the preceding 20 years (odds ratio, 1.36 [1.00 to 1.85]) but were not different in respect to exposure to UV-A or UV-B. These data suggest that high levels of exposure to blue or visible light may cause ocular damage, especially later in life, and may be related to the development of age-related macular degeneration.

Relationship of drusen and abnormalities of the retinal pigment epithelium to the prognosis of neovascular macular degeneration. The Macular Photocoagulation Study Group.

We graded macular features of 127 fellow eyes of participants in the Macular Photocoagulation Study who had an extrafoveal choroidal neovascular membrane secondary to age-related macular degeneration in the first eye and no initial evidence of the neovascular form of age-related macular degeneration in the fellow eye. Our aims were to determine the relationship of drusen characteristics and retinal pigment epithelial abnormalities to the risk of subsequent development of neovascularization in the fellow eye and the risk of subsequent development of recurrent neovascular membranes after photocoagulation in the first eye. Regression analysis demonstrated that the presence of large drusen and focal hyperpigmentation of the retinal pigment epithelium were independent risk factors for the subsequent development of neovascularization in the fellow eye (relative risk, 2.4 and 2.5, respectively). Only 10% of eyes with no large drusen or any retinal pigment epithelial hyperpigmentation compared with 58% of eyes with both large drusen and retinal pigment epithelial hyperpigmentation developed neovascularization in the fellow eye within 5 years. Using multivariate Cox regression analysis, we noted that the risk of developing recurrent neovascular membranes in the first eye was significantly increased when large drusen (relative risk, 2.8) were noted in the fellow eye at the time of laser treatment in the first eye. Fundus features in the fellow eye appear to help identify patients at high risk of developing visual loss from recurrent neovascular membranes following laser treatment in the first eye and from development of a neovascular membrane in the fellow eye.

The grading and prevalence of macular degeneration in Chesapeake Bay watermen.

A new grading scheme was developed to classify the fundus features of macular degeneration. This scheme identifies the earliest fundus changes associated with macular degeneration, as well as specific drusen characteristics felt to be associated with an increased risk of developing the exudative forms of this disease. Agreement between two graders using this scheme indicated good interobserver reliability. Using this scheme, fundus photographs of 777 participants were graded in a population-based study of watermen from the eastern shore of Maryland. The prevalence of at least one druse within 1500 microns of the foveal center was extremely common (over 80% in each age group over 30 years of age) and not age related. The prevalence of large, confluent, or soft drusen was relatively uncommon and was age related; by the eighth decade, 26% of all participants had large or soft drusen, and 17% of them had confluent drusen. These latter characteristics are more likely to be markers of early changes consistent with age-related macular degeneration rather than simply the presence of a few drusen.

Clinicopathologic correlation of occult choroidal neovascularization in age-related macular degeneration.

We report the clinicopathologic features of an eye with occult choroidal neovascularization associated with age-related macular degeneration. Ophthalmoscopic findings at presentation included subretinal fluid and lipid. We noted angiographic staining of irregularly elevated areas of retinal pigment epithelium. In the late phase of the angiogram, fluorescein leakage at the level of the outer retina was observed that did not correspond to well-demarcated areas of hyperfluorescence in earlier phases. The patient was randomized to treatment in a pilot trial comparing the effects of grid laser treatment with the effects of no treatment for occult choroidal neovascularization. Three weeks after treatment, some of the subretinal fluid had cleared and vision improved. The patient died 6 weeks after laser treatment. Histopathologic study disclosed a subretinal pigment epithelial fibrovascular membrane. Neovascularization originated from the choroid.

Choroidal neovascularization in black patients.

OBJECTIVE: To characterize choroidal neovascularization (CNV) in black patients examined at a retinal disease referral center. DESIGN: Retrospective review of the medical records of all patients diagnosed as having CNV to identify black patients with CNV. SETTING: Single tertiary retinal referral center that included four ophthalmologists. PATIENTS: All patients diagnosed as having CNV between April 1990 and October 1992. MAIN OUTCOME MEASURES: Prevalence, demographic information, fundus photographic and fluorescein angiographic characteristics, natural history, and response to laser photocoagulation of CNV in black patients. RESULTS: Black patients comprise 15% of all patients seen at this center. Of 1725 patients identified as having CNV who were seen at the center during a 2.5-year period, only 25 were black (1.4%). In these patients, CNV was associated with a variety of retinal diseases, the most frequent being age-related macular degeneration. The average age of the study group was 54 years, women outnumbered men 2:1, and 13 of the patients developed bilateral lesions. Twelve of the 38 lesions were extrafoveal on presentation, and five of these were peripapillary. In the laser-treated eyes, recurrence of CNV was frequent and associated with visual loss. CONCLUSIONS: Choroidal neovascularization seems to be rare in blacks among a retinal disease referral center population. The overall presentation, natural history, and response to laser treatment seems to be similar to that of white patients. No feature of CNV in black patients was identified that would suggest that results of randomized clinical trials of laser photocoagulation for CNV are not valid for these patients.

Are antioxidants or supplements protective for age-related macular degeneration?

OBJECTIVES: The relationships between fasting plasma levels of retinol, ascorbic acid, alpha-tochopherol, and beta-carotene and age-related macular degeneration (AMD) were studied in a population enrolled in the Baltimore Longitudinal Study of Aging (BLSA), in which most of the data were collected 2 or more years before assessment of macular status. DESIGN: A total of 976 participants in the study were scheduled for a biennial examination from January 1988 through January 1, 1990, which included taking lens and macular photographs. A total of 827 (85%) of the participants had fundus photographs taken, and most plasma data were available for 82% of those subjects with fundus photographs. Age-related macular degeneration was defined as neovascular changes, geographic and nongeographic atrophy, large or confluent drusen, or hyperpigmentation. A total of 226 cases of AMD were available for analysis. RESULTS: Logistic regression analyses suggested that alpha-tocopherol was associated with a protective effect for AMD, adjusted for age, sex, and nuclear opacity. An antioxidant index, including ascorbic acid, alpha-tocopherol, and beta-carotene, was also protective for AMD. Our conclusions must be tempered with the knowledge that the population under study was basically well nourished, and few individuals had any clinically deficient status. The study cannot exclude the possibility that quite low levels of micronutrients, lower than those observed in this study, might be risk factors for AMD. CONCLUSIONS: The data suggest a protective effect for AMD of high plasma values of alpha-tocopherol. An antioxidant index, composed of plasma ascorbic acid, alpha-tocopherol, and beta-carotene, was also protective. The use of vitamin supplements to prevent AMD is not supported by these data, which showed no protective effect of vitamin use.

Availability of color fundus photographs from previous visit affects practice patterns for patients with diabetes mellitus.

OBJECTIVE: To determine whether access to color fundus photographs from a patient's previous visit would alter the recommendations rendered to a cohort with diabetic retinopathy. PATIENTS AND METHODS: One hundred sixty patients with diabetic retinopathy returning for a follow-up visit and who had color fundus photographs obtained at a previous visit were evaluated by trained retina specialists. Their clinical impression and recommendations regarding management of diabetic retinopathy were recorded without reference to previous photographs. Color fundus photographs from the patient's most recent visit were then reviewed and new recommendations with regard to appropriate treatment and follow-up were recorded. RESULTS: In 21% of cases, after reviewing the patient's most recent color fundus photographs, the clinical recommendation changed. In 14% of cases, photographs clearly demonstrated that the patient's condition was stable or improved, resulting in a change from recommending treatment to recommending deferral of treatment. In 4% of cases, photographs clearly demonstrated clinical worsening and the recommendation was changed from observation to treatment. In 3% of cases, review of photographs prompted a change in the recommended follow-up interval. CONCLUSION: Access to color fundus photographs from a patient's previous visit frequently changed the clinical recommendations made to patients with diabetic retinopathy regarding appropriate treatment and follow-up. Availability of color fundus photographs therefore has implications about quality of care and may affect the cost of care.

Exposure to sunlight and other risk factors for age-related macular degeneration.

As some ultraviolet (UV) radiation is transmitted by the ocular media, there is a growing concern that there may be a possible relationship between long-term exposure to ultraviolet radiation and increased risk of age-related macular degeneration. To address this question, a survey was conducted of 838 Maryland watermen who had well-characterized ocular UV-A and UV-B exposure. Fundus photographs were taken and graded for presence of exudative disease, geographic atrophy, focal hyperpigmentation of the retinal pigment epithelium, and drusen that were large and/or confluent. None of the subjects in these analyses were aphakic. The results suggested that age-related macular degeneration was not associated with cumulative exposure to either UV-A or UV-B. Age and the presence of nuclear opacity were independently associated with an increased risk of macular degeneration. Thus, we found that in phakic subjects, even with high levels of sunlight exposure, there was no evidence of increased risk of age-related macular degeneration associated with UV-B or UV-A exposure.

Cigarette smoking and risk for progression of nuclear opacities.

OBJECTIVE: To examine the relationships between smoking and the 5-year incidence of new nuclear opacities and between smoking and the progression of nuclear opacities in a prospective study of a cohort of Chesapeake Bay watermen. METHODS: A total of 442 men (age, > or = 30 years in 1985) with paired, gradable lens photographs in at least one eye in both 1985 and 1990 were studied. Photographs were graded by two readers who used the grading scheme of the Wilmer Institute, Baltimore, Md, with severity ranging in decimal units between 0.0 and 4.0. Data on the smoking history of the subjects were collected by personal interviews that were conducted in 1985 and updated in 1990. RESULTS: The incidence and progression of opacities increased with age. A nonsignificant association was observed between smoking (for both current and ex-smokers) and the incidence of a nuclear opacity. The risk of progression of nuclear opacities of less than grade 3 at baseline to grade 3 or worse was 2.4-fold higher among current smokers in 1985, compared with that among ex-smokers and nonsmokers (95% confidence limits: 1.0, 6.0) after adjustment for age, baseline opacity status, and alcohol use. An 18% increased risk of progression was significantly associated with each pack-year that a subject smoked between 1985 and 1990. CONCLUSION: These data confirm previous findings that smoking is associated with a nuclear opacity, particularly with progression to severe opacities.