Mitochondrial Haplogroups Modify the Effect of Diabetes Duration and HbA1c on Proliferative Diabetic Retinopathy Risk in Patients With Type 2 Diabetes.

Purpose: We previously demonstrated an association between European mitochondrial haplogroups and proliferative diabetic retinopathy (PDR). The purpose of this study was to determine how the relationship between these haplogroups and both diabetes duration and hyperglycemia, two major risk factors for diabetic retinopathy (DR), affect PDR prevalence. Methods: Our population consisted of patients with type 2 diabetes with (n = 377) and without (n = 480) DR. A Kruskal-Wallis test was used to compare diabetes duration and hemoglobin A1c (HbA1c) among mitochondrial haplogroups. Logistic regressions were performed to investigate diabetes duration and HbA1c as risk factors for PDR in the context of European mitochondrial haplogroups. Results: Neither diabetes duration nor HbA1c differed among mitochondrial haplogroups. Among DR patients from haplogroup H, longer diabetes duration and increasing HbA1c were significant risk factors for PDR (P = 0.0001 and P = 0.011, respectively). Neither diabetes duration nor HbA1c was a significant risk factor for PDR in DR patients from haplogroup UK. Conclusions: European mitochondrial haplogroups modify the effects of diabetes duration and HbA1c on PDR risk in patients with type 2 diabetes. In our patient population, longer diabetes duration and higher HbA1c increased PDR risk in patients from haplogroup H, but did not affect PDR risk in patients from haplogroup UK. This relationship has not been previously demonstrated and may explain, in part, why some patients with nonproliferative DR develop PDR and others do not, despite similar diabetes duration and glycemic control.

Mitochondrial Haplogroups Affect Severity But Not Prevalence of Diabetic Retinopathy.

Purpose: We previously reported European mitochondrial haplogroup H to be a risk factor for and haplogroup UK to be protective against proliferative diabetic retinopathy (PDR) among Caucasian patients with diabetic retinopathy (DR). The purpose of this study was to determine whether these haplogroups are also associated with the risk of having DR among Caucasian patients with diabetes. Methods: Deidentified medical records for 637 Caucasian patients with diabetes (223 with DR) were obtained from BioVU, Vanderbilt University's electronic, deidentified DNA databank. An additional 197 Caucasian patients with diabetes (98 with DR) were enrolled from the Vanderbilt Eye Institute (VEI). We tested for an association between European mitochondrial haplogroups and DR status. Results: The percentage of diabetes patients with DR did not differ across the haplogroups (P = 0.32). The percentage of patients with nonproliferative DR (NPDR; P = 0.0084) and with PDR (P = 0.027) significantly differed across the haplogroups. In logistic regressions adjusting for sex, age, diabetes type, duration of diabetes, and hemoglobin A1c, neither haplogroup H nor haplogroup UK had a significant effect on DR compared with diabetic controls. Haplogroup UK was a significant risk factor (OR = 1.72 [1.13-2.59], P = 0.010) for NPDR compared with diabetic controls in the unadjusted analysis, but not in the adjusted analysis (OR = 1.29 [0.79-2.10], P = 0.20). Conclusions: Mitochondrial haplogroups H and UK were associated with severity, but not presence, of DR. These data argue that the effect of these haplogroups is related to ischemia and neovascularization, the defining features of PDR.

Precision of Epithelial Defect Measurements.

PURPOSE: To ensure optimal care of patients, cornea specialists measure corneal features, including epithelial defects (ED), with slit-lamp calipers. However, caliper measurements are subject to interphysician variability. We examined the extent of variability in ED measurements between cornea specialists and discuss the potential clinical impact. METHODS: A total of 48 variably sized EDs were created in pig eyes. Three cornea specialists measured the maximum vertical and horizontal ED lengths to the nearest 10th of a millimeter using slit-lamp microscopy. An absolute difference in ED measurement between cornea specialists of 0.5 mm was chosen to be the a priori threshold for clinical significance and was evaluated by the Wilcoxon signed-rank test. Interrater reliability was assessed by intraclass correlation coefficients. RESULTS: The average absolute difference in the vertical ED length between pairs of examiners ranged from 0.54 to 0.63 mm, and that of the horizontal ED length ranged from 0.44 to 0.46 mm. These differences in ED measurement were not significantly different from 0.5 mm (all P > 0.06). However, pairs of examiners differed in vertical ED length measurements by >0.5 mm in 44% to 52% of EDs and by >1.0 mm in 13% to 17% of EDs. Pairs of examiners differed in horizontal ED length measurements by >0.5 mm in 31% to 40% of EDs and by >1.0 mm in 10% to 15% of EDs. The intraclass correlation coefficient was 0.85 (95% confidence interval, 0.77-0.91) for vertical and 0.84 (95% confidence interval, 0.74-0.90) for horizontal ED measurements. CONCLUSIONS: Cornea specialists showed good reliability in the measured EDs; however, depending on the threshold for clinical significance, a nontrivial percentage of cases have high interexaminer clinical variability.

Geographic Disparities in the Etiology of Bacterial and Fungal Keratitis in the United States of America.

Infectious keratitis is a serious cause of vision loss. Proper treatment of infectious keratitis requires antimicrobials that target the organism responsible for a patient's ulcer. The frequency of infection by a given organism varies by location. We examined the literature to determine geographic disparities in the etiology of bacterial and fungal keratitis in the United States of America. Bacterial keratitis makes up a greater proportion of cases in northern locations, and fungal keratitis increases in prevalence in southern locations. Gram-negative organisms make up a greater proportion of bacterial keratitis in southern locations when compared to northern locations.

Mitochondrial haplogroups are associated with severity of diabetic retinopathy.

PURPOSE: To determine if specific mitochondrial haplogroups associate with nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). METHODS: Deidentified medical records for Caucasian patients with diabetic retinopathy (DR; 153 NPDR and 138 PDR) were obtained from BioVU, Vanderbilt University's electronic, deidentified DNA databank. An independent cohort of Caucasian patients with DR (44 NPDR and 57 PDR) from the Vanderbilt Eye Institute (VEI) was used for validation. We tested for an association between mitochondrial haplogroups and PDR among patients with DR. RESULTS: In the BioVU cohort, PDR frequency among Caucasian DR patients differed significantly by mitochondrial haplogroup (P = 0.027). Replication in the VEI cohort confirmed this association (P = 0.0064). In the combined cohort, patients from the common haplogroup H were more likely to have PDR (odds ratio [OR] = 2.0 [95% confidence interval (CI) = 1.3-3.0], P = 0.0012), while patients from haplogroup Uk were less likely to have PDR (OR = 0.5 [95% CI = 0.3-0.8], P = 0.0049). In logistic regression analyses, the addition of diabetes duration, hemoglobin A1c (HgbA1c) levels, and hypertension had no effect on the associations of haplogroups H and Uk with PDR. CONCLUSIONS: In this study, DR patients from mitochondrial haplogroup H were more likely to have PDR, while DR patients from haplogroup Uk were less likely to have PDR. The association was independent of the major clinical variables affecting PDR. The mitochondrial haplogroups were as strong a risk factor for PDR as were elevated HgbA1c levels.

Retinoblastoma detected by preschool vision screening using visual-evoked potentials.

Two cases of otherwise healthy children with no known family history of retinoblastoma who were diagnosed as having retinoblastoma after failing a visual-evoked potential test during a well-child visit are reported. This early detection allowed for eye-sparing treatment.

Access to ophthalmologic care in Thailand: a regional analysis.

PURPOSE: The World Health Organization (WHO) recommends that Southeast Asian countries have ≥ 1 ophthalmologist per 100,000 persons, equally distributed in urban and rural areas. However, regional patterns of eye care have been poorly characterized. This study investigates the distribution of ophthalmologists in Thailand and provides regional estimates of access to ophthalmologists. METHODS: We geocoded the work address of ophthalmologists listed in the 2008 directory of the Royal College of Ophthalmologists of Thailand. We determined the number of ophthalmologists per 100,000 persons at the national, provincial, and district levels using data from the 2000 Thai Population Census, and assessed demographic factors associated with meeting the WHO recommendation of ≥ 1 ophthalmologist per 100,000 persons. RESULTS: In 2008, Thailand had 1.52 ophthalmologists per 100,000 persons; however, only 20 of 76 provinces (26%) and 134 of 926 districts (14%) met the WHO recommendation of ≥ 1 ophthalmologist per 100,000 persons. District factors associated with not meeting the WHO recommendation included a high proportion of children, a high proportion of elderly, and a high proportion of rural residents. CONCLUSION: Thailand meets the WHO's goal for access to ophthalmologic care, but the distribution of ophthalmologists is uneven, with less access to ophthalmologic care in rural areas.

Availability of volunteer-led home-based care system and baseline factors as predictors of clinical outcomes in HIV-infected patients in rural Zambia.

BACKGROUND: We assessed the impact of home-based care (HBC) for HIV+ patients, comparing outcomes between two groups of Zambians receiving antiretroviral therapy (ART) who lived in villages with and without HBC teams. METHODS: We conducted a retrospective cohort study using medical charts from Macha Mission Hospital, a hospital providing HIV care in Zambia's rural Southern Province. Date of birth, date of ART initiation, place of residence, sex, body mass index (BMI), CD4+ cell count, and hemoglobin (Hgb) were abstracted. Logistic regression was used to test our hypothesis that HBC was associated with treatment outcomes. RESULTS: Of 655 patients, 523 (80%) were eligible and included in the study. There were 428 patients (82%) with favorable outcomes (alive and on ART) and 95 patients (18%) with unfavorable outcomes (died, lost to follow-up, or stopped treatment). A minority of the 523 eligible patients (n = 84, 16%) lived in villages with HBC available. Living in a village with HBC was not significantly associated with treatment outcomes; 80% of patients in a village with HBC had favorable outcomes, compared to 82% of patients in a village without HBC (P = 0.6 by χ(2)). In bivariable analysis, lower BMI (P<0.001), low CD4+ cell count (P = 0.02), low Hgb concentration (P = 0.02), and older age at ART initiation (P = 0.047) were associated with unfavorable outcomes. In multivariable analysis, low BMI remained associated with unfavorable outcomes (P<0.001). CONCLUSIONS: We did not find that living in a village with HBC available was associated with improved treatment outcomes. We speculate that the ART clinic's rigorous treatment preparation before ART initiation and continuous adherence counseling during ART create a motivated group of patients whose outcomes did not improve with additional HBC support. An alternative explanation is that the quality of the HBC program is suboptimal.

Retinoblastoma in a child after normal autorefraction and traditional vision screening.

Retinoblastoma is an ocular malignancy that can put a patient's sight and, in some instances, life at risk. Here we report the case of a 2-year-old child who presented to her pediatrician with a 2-week history of left-sided leukocoria caused by retinoblastoma. Results of traditional office-based vision screening and automated vision screening, which often identify but are not specifically designed to detect rare diseases such as retinoblastoma, had been normal in the antecedent 7 months. She underwent enucleation of the left eye and has done well postoperatively. This case highlights the importance of assessing ocular media clarity by using red-reflex testing at multiple intervals during the preschool years, particularly in light of the recently published US Preventive Services Task Force guidelines for preschool vision screening, which gave an "insufficient evidence" level for vision screening in children younger than 3 years and failed to address red-reflex examination.