Ritch, Robert

Abstract Purpose: To compare vascular parameters, assessed by endothelin-1 (ET-1) blood levels, Laser Doppler Imaging (LDI) of distal phalanx, and nailfold capillaroscopy (NC), between open-angle glaucoma (OAG) patients with low (LTDH) and high-tension optic disc hemorrhages (HTDH). Methods: In this prospective study, patients were classified as LTDH if presenting an IOP<16 mmHg and HTDH if an IOP³16 mmHg at the time of DH detection. Demographic and ophthalmological data, ET-1 concentration, LDI (before and after 1, 10 and 20 minutes after cold stimulation) and NC findings were evaluated. Results: Thirty-tree patients were included (mean age, 62.3±13 years). Regarding ET-1 blood level, it was 65% higher in the LTDH group (2.27±1.46 pg/ml) compared to the HTDH (1.37±0.57 pg/ml; p=0.03). In addition, there was a significant negative correlation between ET-1 blood concentration and IOP at the time of DH detection (r=-0.45; p=0.02). Blood flow measurement in LTDH patients were lower than those observed in patients with HTDH 10 and 20 minutes after cold stimulus (p<0.01). Conclusion: Patients developing DH with lower IOPs have higher ET-1 blood levels and more peripheral vascular dysfunction (than those with higher IOPs), as estimated by LDI. These findings suggest that distinct underling mechanisms maybe involved in patients developing DH with different IOP ranges.

Abstract Objective: Several attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG. Methods: Using data from the Nurses’ Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method. Results: The genetic risk score was associated with self-reported ANM (P = 2.2 × 10–77) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P ≥0.20). Compared to the middle 80 percent, there was also no association with the lowest 10th percentile or highest 90th percentile of genetic risk score with POAG (OR = 0.75; 95% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95% CI: 0.72, 1.69; P = 0.65, respectively). Conclusions: A genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.

AbstractBackgroundTo investigate anatomical configuration of ciliary body and iris using ultrasound biomicroscopy as a predictor of malignant glaucoma development.DesignRetrospective study in a tertiary care hospital.ParticipantsCohort of 31 consecutive patients diagnosed with post‐surgical malignant glaucoma.MethodsAnterior chamber angle, iris and ciliary body configuration of involved eyes that had ultrasound biomicroscopy evaluation prior to the malignant glaucoma onset were evaluated. In cases with no presurgical ultrasound biomicroscopy exam of the involved eye, images from the fellow eye (imaged within 6 months) were analysed.Main Outcome MeasuresQualitative parameters.ResultsThirty‐one eyes (31 patients) had confirmed malignant glaucoma between 1996 and 2008. Most patients were women (65%) and had an anatomical narrow angle or angle‐closure glaucoma (77%). Mean intraocular pressure at diagnosis was 30.4 ± 13.5 mmHg. The most common operation was trabeculectomy with mitomycin C (55%, 17/31 eyes), combined (3/17) or not (14/17) with cataract extraction and intraocular lens implantation. Among these 31 cases, we were able to evaluate the ultrasound biomicroscopy images of 13 patients (13 eyes) including involved eyes imaged prior to the malignant glaucoma onset or eligible fellow eyes. A narrow angle with or without iridotrabecular contact was found in all eyes. A large and/or anteriorly positioned ciliary body associated with an iris root angulating forward and centrally, revealing a plateau iris configuration, was noticed in 85% (11/13) of these eyes.ConclusionIdentification of plateau iris configuration by ultrasound biomicroscopy should be considered as a possible predictor of post‐operative malignant glaucoma development.