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James B. Herrick's 1910 article presenting the case of an anemic West Indian student with peculiar-shaped red blood cells was the first description of sickle cell anemia in Western medical literature. However, he told only part of the story. Records in Chicago, Washington, DC, and Grenada, West Indies, reveal more information about the events surrounding Herrick's discovery and help put them in historical perspective. Herrick's intern, Ernest E. Irons, abreast of the latest developments in medicine, actually performed the blood work and alerted Herrick about the odd-looking cells. Changing patterns in American race relations allowed the patient, Walter Clement Noel, to study dentistry in Chicago. He continued to receive care from Irons for 2 1/2 years, then returned to Grenada to practice dentistry. Noel died nine years after his return to Grenada, at age 32. [ABSTRACT FROM AUTHOR]

Discusses the association of syphilis to drug use and prostitution in Connecticut and Philadelphia, Pennsylvania. Annual rates of syphilis; Use of the information on patients' lifestyles to help locate sexual contacts; Decrease in the proportion of men with syphilis who reported sexual contact with men.

Importance: Cardiovascular health may be used for prevention of depressive symptoms. However, data on the association of cardiovascular health across midlife with depressive symptoms are lacking., Objective: To evaluate whether better baseline cardiovascular health and improvement of cardiovascular health over time are associated with a lower risk of both incident depressive symptoms and unfavorable trajectories of depressive symptoms., Design, Setting, and Participants: Participants without depressive symptoms were included from a prospective community-based cohort in France (GAZEL cohort). Cardiovascular health examinations occurred in 1990 and 1997 and assessment of depressive symptoms in 1997 and every 3 years thereafter until 2015. Data were analyzed from January to October 2022., Exposures: Number of cardiovascular health metrics (smoking, body mass index, physical activity, diet, blood pressure, glucose, and cholesterol) at an intermediate or ideal level in 1997 (range, 0-7) and 7-year change in cardiovascular health between 1990 and 1997., Main Outcomes and Measures: Primary outcome was incident depressive symptoms (20-item Center for Epidemiologic Studies-Depression Scale [CES-D] score of 17 or greater in men or 23 or greater in women); secondary outcome was trajectories of depressive symptoms scores. Trajectories included consistently low scores, moderately elevated scores, low starting then increasing scores, moderately high starting, increasing, then remitting scores, and moderately high starting then increasing scores., Results: Of 6980 included patients, 1671 (23.9%) were women, and the mean (SD) age was 53.3 (3.5) years. During a follow-up spanning 19 years after 1997, 1858 individuals (26.5%) had incident depressive symptoms. Higher baseline cardiovascular health in 1997 and improvement in cardiovascular health over 7 years were each associated with lower risk of depressive symptoms (odds ratio [OR] per additional metric at intermediate or ideal level at baseline, 0.87; 95% CI, 0.84-0.91; OR per 1 higher metric at intermediate or ideal level over 7 years, 0.91; 95% CI, 0.86-0.96). Also, better cardiovascular health was associated with lower risk of unfavorable depressive symptoms trajectories. Compared with the consistently low score trajectory, the lowest risks were observed for the low starting then increasing score trajectory (OR per additional metric at intermediate or ideal level at baseline, 0.70; 95% CI, 0.64-0.76; OR per 1 higher metric at intermediate or ideal level over 7 years, 0.73; 95% CI, 0.68-0.79) and the moderately high starting then increasing score trajectory (OR per additional metric at intermediate or ideal level at baseline, 0.71; 95% CI, 0.64-0.79; OR per 1 higher metric at intermediate or ideal level over 7 years, 0.71; 95% CI, 0.64-0.77)., Conclusions and Relevance: In this prospective community-based cohort study of adults, higher cardiovascular health was associated with a lower risk of depressive symptoms over time. Elucidating which set of cardiovascular factors may affect depression risk could be important for prevention.

Importance: Persistent symptoms after SARS-CoV-2 infection are an emerging public health problem. The duration of these symptoms remains poorly documented., Objective: To describe the temporal dynamics of persistent symptoms after SARS-CoV-2 infection and the factors associated with their resolution., Design, Setting, and Participants: This cross-sectional study involved 53 047 participants from 3 French adult population-based cohorts (CONSTANCES [Consultants des Centres d'Examens de Santé], E3N/E4N, and Nutrinet-Santé) who were included in a nationwide survey about SARS-CoV-2 infection. All participants were asked to complete self-administered questionnaires between April 1 and June 30, 2020. Variables included sociodemographic characteristics, comorbid conditions, COVID-19 diagnosis, and acute symptoms. Blood samples were obtained for serologic analysis between May 1 and November 30, 2020, from patients with SARS-CoV-2 infection defined as enzyme-linked immunosorbent assay immunoglobulin G antispike detection confirmed with a neutralization assay. A follow-up internet questionnaire was completed between June 1 and September 30, 2021, with details on persistent symptoms, their duration, and SARS-CoV-2 infection diagnosis by polymerase chain reaction., Main Outcomes and Measures: Persistent symptoms were defined as symptoms occurring during the acute infection and lasting 2 or more months. Survival models for interval-censored data were used to estimate symptom duration from the acute episode. Multivariable adjusted hazard ratios (HRs) were estimated for age, sex, and comorbid conditions. Factors associated with the resolution of symptoms were assessed., Results: A total of 3972 participants (2531 women [63.7%; 95% CI, 62.2%-65.2%]; mean [SD] age, 50.9 [12.7] years) had been infected with SARS-CoV-2. Of these 3972 participants, 2647 (66.6% [95% CI, 65.1%-68.1%]) reported at least 1 symptom during the acute phase. Of these 2647 participants, 861 (32.5% [95% CI, 30.8%-34.3%]) reported at least 1 persistent symptom lasting 2 or more months after the acute phase. After 1 year of follow-up, the estimated proportion of individuals with complete symptom resolution was 89.9% (95% CI, 88.7%-90.9%) with acute symptoms. Older age (>60 years; HR, 0.78; 95% CI, 0.68-0.90), female sex (HR, 0.64; 95% CI, 0.58-0.70), history of cancer (HR, 0.61; 95% CI, 0.47-0.79), history of tobacco consumption (HR, 0.80; 95% CI, 0.73-0.88), high body mass index (≥30: HR, 0.75; 95% CI, 0.63-0.89), and high number of symptoms during the acute phase (>4; HR, 0.43; 95% CI, 0.39-0.48) were associated with a slower resolution of symptoms., Conclusions and Relevance: In this cross-sectional study, persistent symptoms were still present in 10.1% of infected individuals at 1 year after SARS-CoV-2 infection. Given the high level of cumulative incidence of COVID-19, the absolute prevalent number of people with persistent symptoms is a public health concern.

Importance: Although hearing loss is common in the population worldwide, the prevalence of hearing loss and hearing aid use is not known., Objective: To estimate the prevalence of hearing loss and hearing aid use in the adult French population., Design, Setting, and Participants: This cohort study used data from the CONSTANCES cohort, a representative sample of the French population. Volunteers aged 18 to 75 years were recruited at 21 preventive health centers between January 1, 2012, and December 31, 2019. The present study included participants with audiometric data., Main Outcomes and Measures: The main outcomes were prevalence of hearing loss and disabling hearing loss overall and by sex and age group and prevalence of self-reported hearing aid use among those with disabling hearing loss. Hearing loss was defined as a pure-tone average (PTA) in the better ear of 20 dB or higher, and disabling hearing loss was defined as a PTA in the better ear of 35 dB or higher., Results: Of 200 870 participants in the CONSTANCES study, 186 460 had full audiometric data and were included in this study (mean [SD] age, 47.1 [13.5] years); 100 330 (53.8%) were female, and 86 130 (46.2%) were male. Of these participants, 24.8% (95% CI, 24.6%-25.0%) had hearing loss and 4.3% (95% CI, 4.2%-4.4%) had disabling hearing loss. The prevalence rates of hearing loss increased from 3.4% (95% CI, 2.8%-3.9%) at age 18 to 25 years to 73.3% (95% CI, 69.5%-77.2%) at age 71 to 75 years among men and from 4.4% (95% CI, 3.9%-5.0%) at age 18 to 25 years to 64.1% (95% CI, 59.7%-68.4%) at age 71 to 75 years among women. The prevalence of disabling hearing loss increased from 0.3% (95% CI, 0.2%-0.4%) among participants aged 18 to 25 years to 23.3% (95% CI, 20.7%-26.0%) among participants aged 71 to 75 years. Among the 8050 participants with disabling hearing loss, 36.8% (95% CI, 35.8%-37.9%) reported using hearing aids, including 56.7% (95% CI, 38.9%-74.4%) aged 18 to 25 years and 32.9% (95% CI, 26.8%-39.2%) aged 71 to 75 years., Conclusions and Relevance: In this cohort study, hearing loss was prevalent in France, and the prevalence of hearing loss increased with age among both men and women. Hearing aids were underused, particularly among older individuals. These findings suggest that hearing loss prevention and screening in the French population are needed.

Importance: After an infection by SARS-CoV-2, many patients present with persistent physical symptoms that may impair their quality of life. Beliefs regarding the causes of these symptoms may influence their perception and promote maladaptive health behaviors., Objective: To examine the associations of self-reported COVID-19 infection and SARS-CoV-2 serology test results with persistent physical symptoms (eg, fatigue, breathlessness, or impaired attention) in the general population during the COVID-19 pandemic., Design, Setting, and Participants: Participants in this cross-sectional analysis were 26 823 individuals from the French population-based CONSTANCES cohort, included between 2012 and 2019, who took part in the nested SAPRIS and SAPRIS-SERO surveys. Between May and November 2020, an enzyme-linked immunosorbent assay was used to detect anti-SARS-CoV-2 antibodies. Between December 2020 and January 2021, the participants reported whether they believed they had experienced COVID-19 infection and had physical symptoms during the previous 4 weeks that had persisted for at least 8 weeks. Participants who reported having an initial COVID-19 infection only after completing the serology test were excluded., Main Outcomes and Measures: Logistic regressions for each persistent symptom as the outcome were computed in models including both self-reported COVID-19 infection and serology test results and adjusting for age, sex, income, and educational level., Results: Of 35 852 volunteers invited to participate in the study, 26 823 (74.8%) with complete data were included in the present study (mean [SD] age, 49.4 [12.9] years; 13 731 women [51.2%]). Self-reported infection was positively associated with persistent physical symptoms, with odds ratios ranging from 1.39 (95% CI, 1.03-1.86) to 16.37 (95% CI, 10.21-26.24) except for hearing impairment (odds ratio, 1.45; 95% CI, 0.82-2.55) and sleep problems (odds ratio, 1.14; 95% CI, 0.89-1.46). A serology test result positive for SARS-COV-2 was positively associated only with persistent anosmia (odds ratio, 2.72; 95% CI, 1.66-4.46), even when restricting the analyses to participants who attributed their symptoms to COVID-19 infection. Further adjusting for self-rated health or depressive symptoms yielded similar results. There was no significant interaction between belief and serology test results., Conclusions and Relevance: The findings of this cross-sectional analysis of a large, population-based French cohort suggest that persistent physical symptoms after COVID-19 infection may be associated more with the belief in having been infected with SARS-CoV-2 than with having laboratory-confirmed COVID-19 infection. Further research in this area should consider underlying mechanisms that may not be specific to the SARS-CoV-2 virus. A medical evaluation of these patients may be needed to prevent symptoms due to another disease being erroneously attributed to "long COVID."

Importance: Evidence on alcohol consumption as a risk factor for dementia usually relates to overall consumption. The role of alcohol-induced loss of consciousness is uncertain., Objective: To examine the risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers., Design, Setting, and Participants: Seven cohort studies from the UK, France, Sweden, and Finland (IPD-Work consortium) including 131 415 participants were examined. At baseline (1986-2012), participants were aged 18 to 77 years, reported alcohol consumption, and were free of diagnosed dementia. Dementia was examined during a mean follow-up of 14.4 years (range, 12.3-30.1). Data analysis was conducted from November 17, 2019, to May 23, 2020., Exposures: Self-reported overall consumption and loss of consciousness due to alcohol consumption were assessed at baseline. Two thresholds were used to define heavy overall consumption: greater than 14 units (U) (UK definition) and greater than 21 U (US definition) per week., Main Outcomes and Measures: Dementia and alcohol-related disorders to 2016 were ascertained from linked electronic health records., Results: Of the 131 415 participants (mean [SD] age, 43.0 [10.4] years; 80 344 [61.1%] women), 1081 individuals (0.8%) developed dementia. After adjustment for potential confounders, the hazard ratio (HR) was 1.16 (95% CI, 0.98-1.37) for consuming greater than 14 vs 1 to 14 U of alcohol per week and 1.22 (95% CI, 1.01-1.48) for greater than 21 vs 1 to 21 U/wk. Of the 96 591 participants with data on loss of consciousness, 10 004 individuals (10.4%) reported having lost consciousness due to alcohol consumption in the past 12 months. The association between loss of consciousness and dementia was observed in men (HR, 2.86; 95% CI, 1.77-4.63) and women (HR, 2.09; 95% CI, 1.34-3.25) during the first 10 years of follow-up (HR, 2.72; 95% CI, 1.78-4.15), after excluding the first 10 years of follow-up (HR, 1.86; 95% CI, 1.16-2.99), and for early-onset (<65 y: HR, 2.21; 95% CI, 1.46-3.34) and late-onset (≥65 y: HR, 2.25; 95% CI, 1.38-3.66) dementia, Alzheimer disease (HR, 1.98; 95% CI, 1.28-3.07), and dementia with features of atherosclerotic cardiovascular disease (HR, 4.18; 95% CI, 1.86-9.37). The association with dementia was not explained by 14 other alcohol-related conditions. With moderate drinkers (1-14 U/wk) who had not lost consciousness as the reference group, the HR for dementia was twice as high in participants who reported having lost consciousness, whether their mean weekly consumption was moderate (HR, 2.19; 95% CI, 1.42-3.37) or heavy (HR, 2.36; 95% CI, 1.57-3.54)., Conclusions and Relevance: The findings of this study suggest that alcohol-induced loss of consciousness, irrespective of overall alcohol consumption, is associated with a subsequent increase in the risk of dementia.

Importance: It is well established that selected lifestyle factors are individually associated with lower risk of chronic diseases, but how combinations of these factors are associated with disease-free life-years is unknown., Objective: To estimate the association between healthy lifestyle and the number of disease-free life-years., Design, Setting, and Participants: A prospective multicohort study, including 12 European studies as part of the Individual-Participant-Data Meta-analysis in Working Populations Consortium, was performed. Participants included 116 043 people free of major noncommunicable disease at baseline from August 7, 1991, to May 31, 2006. Data analysis was conducted from May 22, 2018, to January 21, 2020., Exposures: Four baseline lifestyle factors (smoking, body mass index, physical activity, and alcohol consumption) were each allocated a score based on risk status: optimal (2 points), intermediate (1 point), or poor (0 points) resulting in an aggregated lifestyle score ranging from 0 (worst) to 8 (best). Sixteen lifestyle profiles were constructed from combinations of these risk factors., Main Outcomes and Measures: The number of years between ages 40 and 75 years without chronic disease, including type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease., Results: Of the 116 043 people included in the analysis, the mean (SD) age was 43.7 (10.1) years and 70 911 were women (61.1%). During 1.45 million person-years at risk (mean follow-up, 12.5 years; range, 4.9-18.6 years), 17 383 participants developed at least 1 chronic disease. There was a linear association between overall healthy lifestyle score and the number of disease-free years, such that a 1-point improvement in the score was associated with an increase of 0.96 (95% CI, 0.83-1.08) disease-free years in men and 0.89 (95% CI, 0.75-1.02) years in women. Comparing the best lifestyle score with the worst lifestyle score was associated with 9.9 (95% CI 6.7-13.1) additional years without chronic diseases in men and 9.4 (95% CI 5.4-13.3) additional years in women (P < .001 for dose-response). All of the 4 lifestyle profiles that were associated with the highest number of disease-free years included a body-mass index less than 25 (calculated as weight in kilograms divided by height in meters squared) and at least 2 of the following factors: never smoking, physical activity, and moderate alcohol consumption. Participants with 1 of these lifestyle profiles reached age 70.3 (95% CI, 69.9-70.8) to 71.4 (95% CI, 70.9-72.0) years disease free depending on the profile and sex., Conclusions and Relevance: In this multicohort analysis, various healthy lifestyle profiles appeared to be associated with gains in life-years without major chronic diseases.

Importance: The electronic cigarette (EC) has become popular among smokers who wish to reduce their tobacco use levels or quit smoking, but its effectiveness as a cessation aid is uncertain., Objective: To examine the association of regular EC use with the number of cigarettes smoked per day, smoking cessation among current smokers, and smoking relapse among former smokers., Design, Setting, and Participants: The CONSTANCES (Consultants des Centres d'Examens de Santé) cohort study, based in France, began recruiting participants January 6, 2012, and is currently ongoing. Participants were enrolled in CONSTANCES through 2015, and included 5400 smokers (mean [SD] follow-up of 23.4 [9.3] months) and 2025 former smokers (mean [SD] follow-up of 22.1 [8.6] months) at baseline who quit smoking in 2010, the year in which ECs were introduced in France, or afterward. Analyses were performed from February 8, 2017, to October 15, 2018., Main Outcomes and Measures: The association between EC use and the number of cigarettes smoked during follow-up was studied using mixed regression models. The likelihood of smoking cessation was studied using Poisson regression models with robust sandwich variance estimators. The association between EC use and smoking relapse among former smokers was studied using Cox proportional hazards regression models. All statistical analyses were adjusted for sociodemographic characteristics, duration of follow-up, and smoking characteristics., Results: Among the 5400 daily smokers (2906 women and 2494 men; mean [SD] age, 44.9 [12.4] years), regular EC use was associated with a significantly higher decrease in the number of cigarettes smoked per day compared with daily smokers who did not use ECs (-4.4 [95% CI, -4.8 to -3.9] vs -2.7 [95% CI, -3.1 to -2.4]), as well as a higher adjusted relative risk of smoking cessation (1.67; 95% CI, 1.51-1.84]). At the same time, among the 2025 former smokers (1004 women and 1021 men; mean [SD] age, 43.6 [12.1] years), EC use was associated with an increase in the rate of smoking relapse among former smokers (adjusted hazard ratio, 1.70; 95% CI, 1.25-2.30)., Conclusions and Relevance: This study's findings suggest that, among adult smokers, EC use appears to be associated with a decrease in smoking level and an increase in smoking cessation attempts but also with an increase in the level of smoking relapse in the general population after approximately 2 years of follow-up.

Importance: Early breast development is a risk factor for breast cancer, and girls with a breast cancer family history (BCFH) experience breast development earlier than girls without a BCFH., Objectives: To assess whether prepubertal androgen concentrations are associated with timing of breast development (analysis 1) and to compare serum androgen concentrations in girls with and without a BCFH (analysis 2)., Design, Setting, and Participants: Prospective cohort study of 104 girls aged 6 to 13 years at baseline using data collected between August 16, 2011, and March 24, 2016, from the Lessons in Epidemiology and Genetics of Adult Cancer From Youth (LEGACY) Girls Study, New York site., Exposures: Analysis 1 included serum concentrations of dehydroepiandrosterone sulfate, androstenedione, and testosterone (free and total) measured before breast development and divided at the median into high and low categories. Analysis 2 included the degree of BCFH: first-degree was defined as having a mother with breast cancer and second-degree was defined as having a grandmother or aunt with breast cancer., Main Outcomes and Measures: Analysis 1 included age at onset of breast development measured using the Pubertal Development Scale (scores range from 1-4; scores ≥2 indicate breast development), and analysis 2 included serum androgen concentrations. We also assessed breast cancer-specific distress using the 8-item Child Impact of Events Scale., Results: Our analyses included 36 girls for the prospective model, 92 girls for the cross-sectional model, and 104 girls for the longitudinal model. Of the 104 girls, the mean (SD) age at baseline was 10.3 (2.5) years, and 41 (39.4%) were non-Hispanic white, 41 (39.4%) were Hispanic, 13 (12.5%) were non-Hispanic black, and 9 (8.7%) were other race/ethnicity. Forty-two girls (40.4%) had a positive BCFH. Girls with prepubertal androstenedione concentrations above the median began breast development 1.5 years earlier than girls with concentrations below the median (Weibull survival model-estimated median age, 9.4 [95% CI, 9.0-9.8] years vs 10.9 [95% CI, 10.4-11.5] years; P = .001). Similar patterns were observed for dehydroepiandrosterone sulfate (1.1 years earlier: age, 9.6 [95% CI, 9.1-10.1] years vs 10.7 [95% CI, 10.2-11.3] years; P = .009), total testosterone (1.4 years earlier: age, 9.5 [95% CI, 9.1-9.9] years vs 10.9 [95% CI, 10.4-11.5] years; P = .001), and free testosterone (1.1 years earlier: age, 9.7 [95% CI, 9.2-10.1] years vs 10.8 [95% CI, 10.2-11.4] years; P = .01). Compared with girls without BCFH, girls with a first-degree BCFH, but not a second-degree BCFH, had 240% higher androstenedione concentrations (geometric means: no BCFH, 0.49 ng/mL vs first-degree BCFH, 1.8 ng/mL vs second-degree, 1.6 ng/mL; P = .01), 10% higher total testosterone concentrations (12.7 ng/dL vs 14.0 ng/dL vs 13.7 ng/dL; P = .01), and 92% higher free testosterone concentrations (1.3 pg/mL vs 2.5 pg/mL vs 0.3 pg/mL; P = .14). The dehydroepiandrosterone sulfate concentration did not differ between BCFH-positive and BCFH-negative girls but was elevated in girls with breast cancer-specific distress., Conclusions and Relevance: Our findings suggest that androgen concentrations may differ between girls with and without a BCFH and that elevated hormone concentrations during adolescence may be another factor to help explain the familial clustering of breast cancer.

Objective: To identify risk factors associated with higher rates of ocular complications in children with traumatic hyphema., Methods: Consecutive inpatient records from July 1990 through December 1997 were retrospectively reviewed for all children (aged < or = 18 years) who were admitted to the Wilmer Ophthalmological Institute, Baltimore, Md, within 48 hours of a closed-globe injury leading to hyphema. Data obtained included age, sex, race, sickle cell status, initial and final visual acuities, hyphema size and intraocular pressure at presentation, the occurrence of a secondary hemorrhage, subsequent intraocular pressure elevations, and therapeutic interventions., Results: Forty children fulfilled the inclusion criteria: 20 African American, 1 Asian American, and 19 white. Five of the 20 African American children had sickle cell trait, and 1 had sickle cell anemia. The rate of secondary hemorrhage was statistically higher in the African American population (P =.05), but no statistical difference existed between the rate of secondary hemorrhage in patients with and without sickle cell hemoglobinopathy. Sickle cell hemoglobinopathy was associated with a higher intraocular pressure at presentation (P =.03) and during inpatient follow-up (P =.02)., Conclusions: In the setting of traumatic hyphema, African American children appear to be at greater risk for developing a secondary hemorrhage. In our patients, sickle cell hemoglobinopathy increased the risk of intraocular pressure elevation, but did not seem to increase the risk of rebleeding beyond that associated with race. Larger studies are needed to validate these observations.

Objective: To assess the morphologic characteristics of the foveal abnormality in juvenile X-linked retinoschisis using the scanning retinal thickness analyzer (RTA). This characteristic foveal abnormality is present in 83% to 100% of patients with X-linked retinoschisis and has not been demonstrated histopathologically., Methods: The RTA is a noncontact imaging device. The RTA scans an obliquely oriented slit laser beam across the macula to obtain a series of optical cross sections, which are digitized., Participants: The RTA was used to examine 7 eyes of 5 patients with X-linked retinoschisis., Results: The RTA demonstrated foveal schisis in all eyes examined. In 2 eyes of 2 patients, a single schisis cavity, with an inner leaf in a dome-shaped configuration, was present. In 4 eyes of 3 patients, a single schisis cavity containing fine strands was present. Some of these strands partially, and others completely, bridged the cavity. In 1 eye of 1 patient, 2 separate schisis cavities with bridging strands were present in the fovea., Conclusions: Scanning RTA is a noninvasive imaging modality capable of producing optical cross sections that demonstrate the extent and structural details of the foveal schisis in X-linked retinoschisis. Scanning RTA seems to be effective in the detection, characterization, and quantification of foveal schisis.

Objective: To establish a communication between an obstructed retinal vein and the choroid by means of laser in eyes with nonischemic central or branch vein occlusion., Methods: Retrospective review identified eyes with nonischemic central or branch vein occlusion, and with decreasing or persistently decreased visual acuity of 20/100 or worse for 4 months or more before treatment, that received 1 or more sessions of laser photocoagulation to create a chorioretinal anastomosis., Results: Of 24 eyes with central vein occlusion, an anastomosis formed in 9 (38%) within 2 months after treatment, with visual improvement of 6 or more lines in 2 (8%) of 24 eyes, 1 to 3 lines in 5 (21%), and no improvement in 2 (8%). Of 6 eyes with branch vein occlusion, an anastomosis formed in 3 (50%) within 2 months after treatment, with visual improvement of 1 to 3 lines in 2 (33%) of 6 and no improvement in 1 (16%). No permanent, vision-limiting complications occurred during a mean follow-up of 13 months after the first treatment session or 8 months after the last session., Conclusions: Laser photocoagulation of a retinal vein and Bruch's membrane may create a chorioretinal anastomosis in some eyes with a nonischemic vein occlusion. Progression to an ischemic status may possibly be prevented with successful anastomosis formation. Marked visual improvement may occur. Treatment techniques to create reliably an anastomosis with subsequent visual improvement, while minimizing potential complications, continue to evolve.

Objective: To describe a series of patients with proved herpes simplex virus keratitis (herpetic keratitis) who also had documented Acanthamoeba keratitis., Methods: Herpetic keratitis was documented with viral cultures, immunologic stains, or histopathologic examination for multinucleated giant cells in the corneal epithelium. Acanthamoeba organisms were identified using confocal microscopy and epithelial biopsy with hematoxylin-eosin staining. Biopsy of the stroma and epithelium was used to identify Acanthamoeba organisms in 1 case., Results: Cultures for herpes simplex virus were positive in 6 of the 9 cases. Immunologic stains were positive in an additional 2 cases, and in 1 case multinucleated giant cells were present in the epithelium consistent with the diagnosis of herpes simplex virus keratitis. Tandem scanning confocal microscopic findings were positive for Acanthamoeba in 8 of the 9 cases, and all of them demonstrated Acanthamoeba organisms in epithelial scrape biopsy specimens. In 1 case, which was not evaluated with confocal microscopy, Acanthamoeba was detected using a stromal and epithelial biopsy. Two of the 9 patients had a history of contact lens use., Conclusion: Acanthamoeba keratitis may be present as a secondary or opportunistic infection in patients with herpetic keratitis.

Objective: To evaluate patients with incontinentia pigmenti for evidence of cerebrovascular disease using magnetic resonance imaging techniques., Design: A prospective case series of seven patients (four of whom were related) with incontinentia pigmenti using magnetic resonance imaging, magnetic resonance angiography, and multislice proton (1H) magnetic resonance spectroscopic imaging., Setting: The Johns Hopkins Medical Institutions, Baltimore, Md, a tertiary, referred care center., Patients: Seven patients with a diagnosis of incontinentia pigmenti., Results: Five of the seven patients had abnormal magnetic resonance imaging consistent with small-vessel occlusions. Of these five patients, four had normal magnetic resonance angiography and spectroscopic imaging, and one patient had reduced middle cerebral artery flow on magnetic resonance angiography and increased lactate level in the cerebrospinal fluid on spectroscopic imaging. The remaining two patients had normal magnetic resonance imaging and spectroscopic imaging. Of these two patients, one had normal magnetic resonance angiography and the other had a right supraclinoid internal carotid aneurysm. There was substantial concordance between clinical (ophthalmic/neurologic) and imaging abnormalities., Conclusions: The central nervous system changes in patients with incontinentia pigmenti may represent the result of small-vessel occlusive phenomena in the brain. These central nervous system findings may share a common pathophysiologic state with the vascular occlusive disease seen in the retinas of these patients. The changes in the retinal vasculature may serve as a potential marker for central nervous system disease. Physicians should be aware of the systemic and debilitating nature of incontinentia pigmenti.

It is estimated that 49% to 74% of cases of contact lens-associated ulcerative keratitis could be prevented by eliminating overnight wear. Heavy alcohol consumption appears to be associated with all types of cataracts. Cigarette smokers have a nearly threefold greater risk of developing age-related macular degeneration than nonsmokers.

Objective: Norrie's disease (ND) is a rare X-linked hereditary disorder characterized by congenital blindness. A putative gene for ND has been isolated and mapped to Xp11.3. Four point mutations in this gene have been identified recently in patients with ND, thus providing strong evidence that this gene is associated with the disease. We report a new mutation., Design: Clinical findings from the proband were correlated with results from DNA analysis. The proband's DNA was compared with that from his mother, an unaffected brother, and four unrelated normal males., Patient: The proband was a male infant referred for ocular evaluation at 3 months of age., Interventions: The patient was evaluated with a general ocular examination at 4 months of age, a computed tomographic scan at 8 months of age, and then periodic follow-up examinations over the next 7 years. Blood samples were also collected from the proband, his family, and four unrelated normal males. DNA was extracted, amplified using polymerase chain reactions, and then cloned and sequenced., Results/conclusions: We identified a new mutation at codon 128 of the ND gene, a dinucleotide GC-to-AA substitution that changed the normal codon for cysteine, TGC, to TAA, which is a stop codon. Thus, this patient lacks the last six amino acids of the carboxyl terminus of the ND protein. The normal ND protein has 11 cysteines in conserved positions that are proposed to be functionally significant. The mutation at codon 128 occurs at the 10th cysteine and might be expected to alter the function of the ND protein. Since the phenotype of this patient is similar to those of other patients with point mutations in the ND gene, this mutation is likely to be the molecular basis of the phenotype.

Objective: To examine the sickle cell retina in dual perspective (vascular patterns en bloc and structure in serial sections) to gain new insights into sickle cell retinopathy., Methods: We analyzed the retinas of two patients with sickle cell disease (a 54-year-old patient with hemoglobin SC, heterozygous for the S and C mutation in the beta chain of the globin gene, and a 20-month-old patient with sickle cell anemia [SS], homozygous for the S mutation) using the previously described adenosine diphosphatase flat-embedding technique., Results: The dual-perspective analysis afforded by our technique revealed that the primary site of occlusions was located at the precapillary level. An unusual neovascular formation, the hairpin loop, was observed in both patients' retinas and appeared to result from recanalization of the wall of an occluded vessel. Many autoinfarcted pre-retinal neovascular formations were observed in the older SC patient. Two patent preretinal formations were studied in detail and their evolution appeared to be influenced by mechanical factors. The vessels appeared to have been extruded from the retina, perhaps owing to hydrostatic pressure secondary to downstream occlusions. Small pigmented lesions consisting of retinal pigment epithelial cells ensheathing channels that resembled autoinfarcted vessels were found in the eye of the SC patient., Conclusions: This study illustrates unusual morphological features of intraretinal and preretinal neovascularization and of chorioretinal lesions in sickle cell retinopathy and suggests alternative mechanisms for their formation.

Objective: To evaluate the safety and efficacy of the transscleral diode laser for retinopexy in rhegmatogenous retinal detachments., Design: Ten consecutive patients with primary rhegmatogenous retinal detachments underwent scleral buckling surgery, using the transscleral diode laser for retinopexy. Patients were followed up for at least 6 months., Study Participants: Ten patients with primary rhegmatogenous retinal detachments were enrolled. Patients with chronic detachments, a retinal break greater than 90 degrees, history of uveitis or infectious retinopathy, or proliferative vitreoretinopathy were excluded., Main Outcome Measure: Retinal reattachment. Secondary measures: visual acuity and complications, including choroidal, retinal, and vitreous hemorrhage, inflammation, and scleral damage., Results: By 6 months, nine of 10 retinas were successfully repaired following only one operation. The retina of the 10th patient redetached at 6 1/2 weeks owing to proliferative vitreoretinopathy. Following a vitrectomy and retinal reattachment procedure, the retina of the 10th patient has remained attached for 1 year. No significant complications were encountered with the laser retinopexy, although small presumed breaks in Bruch's membrane occurred in three eyes and a moderate scleral thermal effect occurred in two. Visual results in the postoperative course were comparable to those achieved previously with cryotherapy., Conclusion: In this pilot series, transscleral diode laser retinopexy served as a safe and effective means of obtaining chorioretinal adhesion in retinal detachment surgery.

Two patients with choroidal hemangiomas developed choroidal neovascularization. One patient with Sturge-Weber syndrome, a unilateral diffuse choroidal hemangioma, and a serous detachment of the macula was treated with yellow dye laser photocoagulation in a grid pattern to the tumor before glaucoma filtration surgery. Four years after successful laser treatment, the patient developed subfoveal choroidal neovascularization in an area of treatment. A second patient with a circumscribed choroidal hemangioma developed spontaneous subfoveal choroidal neovascularization 12 years after initial diagnosis of the hemangioma. The development of choroidal neovascularization associated with choroidal hemangiomas represents a potential cause of poor visual outcome in these patients.

Tissue plasminogen activator was used to evaluate the clearance of traumatic hyphema in a rabbit model. A neodymium-YAG laser was used to disrupt iris vessels, creating a traumatic hyphema. Tissue plasminogen activator (1800 IU/0.1 mL) was injected into the anterior chamber 24 hours after creation of the hyphema. Two control groups (one receiving balanced salt solution and one receiving no treatment) were used for comparison. A multivariate analysis of covariance indicated that the greatest difference in hyphema clearance between the groups occurred at days 3, 4, and 5. Five days after tissue plasminogen activator treatment, the mean size of the clot remaining in the anterior chamber was 27% of that of the original hyphema. In control eyes, almost 60% of the original clot remained at day 5. Treatment of animals with tissue plasminogen activator doses of 5000 IU and 10,000 IU produced a substantial increase in repeated bleeding episodes in our rabbit model. We concluded that although the use of tissue plasminogen activator in our rabbit model of traumatic hyphema significantly improved clearance of blood from the anterior chamber, the remaining clot was of such size that the clinical benefit was questionable.

In a study of Georgia women aged 40 years and older, 15% made use of prenatal chromosomal diagnosis. There was, however, substantial racial and geographic variation, ranging from a use ratio of 60% among whites in two large urban counties to 0.5% among blacks outside Augusta and Atlanta health districts. This simple population-based epidemiologic analysis suggests that future program planning for genetic services in Georgia should address ways to increase access by rural women, especially blacks. Similar analyses in other states could be used for planning genetic services.

Forty-eight patients (49 eyes) had nonperforating traumatic hyphema. Twenty-eight patients (28 eyes with hyphema) received oral aminocaproic acid, an antifibrinolytic agent, in a dosage of 100 mg/kg every four hours for five days, up to a maximum daily dose of 30 g. Twenty patients (21 eyes with hyphema) received placebo in an identical regimen. One eye treated with aminocaproic acid rebled; seven eyes receiving the placebo rebled. The results of this study show a statistically significant reduction in the incidence of secondary hemorrhage in the patients receiving aminocaproic acid.

The incidence of birth defects increases with maternal age. Recent advances in fetal diagnosis, coupled with elective abortion, offer the older pregnant woman an opportunity to reduce this risk. To determine the magnitude of potential risk reduction, we reviewed the maternal age-specific incidence of infants born with one or more severe birth defects in metropolitan Atlanta from 1968 to 1975, removing from analysis certain anomalies that were preventable by currently available methods. For women aged 35 to 44 years, the risk of bearing an infant with a severe birth defect was reduced to a level comparable with that for younger women. Despite prenatal diagnosis and elective abortion, the risk for women aged 45 years or older, although reduced considerably, was two times greater than that for women aged 34 years or younger.

We performed 400 consecutive pars plana vitrectomies, using the vitrophage. Most patients (68%) showed some degree of visual improvement; only 8% had a decline in visual acuity postoperatively. The major operative complications were controllable bleeding from iris vessels and intravitreal stalks (19%) and retinal tears (2%). No retinal dialysis was noted. The major, early postoperative complications were related to corneal decompensation in 38% of the cases; this persisted beyond two weeks in only 7%. Increased intraocular pressure occurred in 19% and postoperative rubeosis iridis developed in 10% of the diabetic patients. Complications related to rebleeding occurred in 18% of the diabetic patients within the first two weeks, and an additional 9% had late rebleeding. Less frequent complications included one case of endophthalmitis, late retinal detachment in 5%, and phthisis bulbi in 2% of all cases. All complications were considerably more frequent and severe in the diabetic population.

Eight monkeys and five humans were subjected to photocoagulation with single argon laser burns of varying intensity on the optic nerve head. Energies greater than 400 milliwatts, 0.2 second and 100 mu spot size consistently caused neural parenchymal damage, even in the absence of heat-generating pigment epithelium. Papillary burns in monkeys and humans created with powers less than 400 mW showed only small, focal submicroscopic areas of degeneration, and were therefore considered relatively safe except for the occasional involvement of critical foveal fibers in which scotomas of disproportionately greater severity than one would expect from the size of the lesion could result. The threshold for toxicity following peripapillary photocoagulation is lower, because the burned pigment epithelium can radiate heat into the adjacent optic nerve fibers. Normal capillaries within the optic nerve were seldom destroyed or occluded, even after high energy densities. In normal vessels, we have found it impossible to create a highly selective lesion without concurrently causing neural damage about the vessel.

Autosomal dominant vitreoretinochoroidopathy is a newly described fundus dystrophy characterized by abnormal chorioretinal hypopigmentation and hyperpigmentation, usually lying between the vortex veins and the ora serrata for 360 degrees. In this zone, there are a discrete posterior boundary, preretinal punctate white opacities, retinal arteriolar narrowing and occlusion, and, in some cases, choroidal atrophy. Most affected family members have diffuse retinal vascular incompetence, cystoid macular edema, and presenile cataracts. The vitreous is characterized by fibrillar condensation and a moderate number of cells. Electroretinograms are normal in younger affected individuals and are only moderately abnormal in older ones. Preretinal neovascularization, present in the posterior pole, is progressive in the proband. There are no identifiable systemic or skeletal abnormalities, high myopia, optically empty vitreous, lattice degeneration, areas of white-without-pressure, retinal breaks, or retinal detachment; thus, previously described vitreoretinopathies can be excluded from diagnostic consideration. Progression of this diagnostic seems to be extremely slow in most family members.

Two patients with acute retinal necrosis were treated with vitrectomy, intravitreal infusion of acyclovir, and prophylactic scleral buckling procedures. Both patients have had a uneventful postoperative course and a recovery of visual acuity; follow-up has been at five and 14 months. There has been no sign of toxicity from the intravitreally administered acyclovir by electroretinographic or clinical criteria.

With prospective observations we have documented by fluorescein angiography the development of retinal neovascularization in the eyes of patients with sickle cell-hemoglobin C disease (hemoglobin SC). In each patient, arteriolarvenular (AV) anastomoses occurred before the development of neovascular sea fans. To our knowledge, this report constitutes the first such documentation in the literature. New sea fans from AV anastomoses appeared throughout an average interval of 18 months (range, 8 to 36 months) in approximately 21% of young adults with hemoglobin SC. Each year approximately 14% of young patients with hemoglobin SC may develop retinal neovascularization.

A 43-year-old black woman showed ophthalmoscopic evidence of retinal arteriolitis two weeks after being treated for uniocular panuveitis. Angiographic examination suggested that these deposits were not intraluminal or endothelial atherosclerotic emboli or plaques, but were deposits in the outer walls of retinal arterioles. Sequential ophthalmoscopic and angiographic examinations at one-month intervals for 12 months showed no progression or change in location of these deposits. Results of clinical and laboratory investigations suggested the diagnosis of syphilis. We believe it is rare for syphilitic infection to be implicated in the diagnosis of isolated retinal arteriolitis without periphlebitis.

Six patients with proliferative sickle cell retinopathy and vitreous bands were treated with the neodymium-YAG (Nd-YAG) laser to accomplish lysis of avascular traction bands or to clear the media in front of the macula. Transection of bands was possible in five of the six cases but in two of these the effect was only partial. Three cases were satisfactorily treated with the Nd-YAG laser application alone, two eventually required conventional vitreoretinal surgery, and one patient's condition stabilized despite failure of the treatment. Complications from the treatment occurred in three cases and included subretinal (choroidal) hemorrhage, preretinal hemorrhage, microperforation of a retinal vein, and focal areas of damage to the retinal pigment epithelium. Neodymium-YAG vitreolysis may be a useful modality in carefully selected patients with proliferative sickle cell retinopathy, but potentially sight-threatening complications may occur.

Fluorescein angiography during the choroidal phase of perfusion has been used to study the origin of blood vessels comprising neovascular tissue of the disc. These newly formed vessels were shown to derive their blood supply primarily from the uveal circulation rather than from the retinal circulation. This is related to the observation that many normal disc blood vessels originate from the choroidal or posterior ciliary circulation.