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Objective: To report a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) followed by massive unilateral uveal proliferation. Methods: Retrospective case report. Results: A 47-year-old female with history of metastatic ovarian carcinoma initially presented with bilateral vision loss and multifocal red patches on posterior poles consistent with BDUMP. Five years later, she presented with bilateral neovascular glaucoma and unilateral iris and ciliary body mass concerning for malignancy. Enucleation revealed diffuse uveal growth involving almost the entirety of the uveal tract. Conclusions: BDUMP can rarely be associated with uveal proliferation. Routine examinations are recommended to monitor for any changes concerning malignancy. [ABSTRACT FROM AUTHOR]

ObjectiveSeveral 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.MethodsUsing 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.ResultsThe genetic risk score was associated with self-reported ANM (P = 2.2 × 10) 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 10 percentile or highest 90 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).ConclusionsA 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.

Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) is the most common subtype and is a complex trait with multigenic inheritance. Genome-wide association studies have previously identified a significant association between POAG and the SIX6 locus (rs10483727, odds ratio (OR) = 1.32, p = 3.87×10(-11)). SIX6 plays a role in ocular development and has been associated with the morphology of the optic nerve. We sequenced the SIX6 coding and regulatory regions in 262 POAG cases and 256 controls and identified six nonsynonymous coding variants, including five rare and one common variant, Asn141His (rs33912345), which was associated significantly with POAG (OR = 1.27, p = 4.2×10(-10)) in the NEIGHBOR/GLAUGEN datasets. These variants were tested in an in vivo Danio rerio (zebrafish) complementation assay to evaluate ocular metrics such as eye size and optic nerve structure. Five variants, found primarily in POAG cases, were hypomorphic or null, while the sixth variant, found only in controls, was benign. One variant in the SIX6 enhancer increased expression of SIX6 and disrupted its regulation. Finally, to our knowledge for the first time, we have identified a clinical feature in POAG patients that appears to be dependent upon SIX6 genotype: patients who are homozygous for the SIX6 risk allele (His141) have a statistically thinner retinal nerve fiber layer than patients homozygous for the SIX6 non-risk allele (Asn141). Our results, in combination with previous SIX6 work, lead us to hypothesize that SIX6 risk variants disrupt the development of the neural retina, leading to a reduced number of retinal ganglion cells, thereby increasing the risk of glaucoma-associated vision loss.

Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) is the most common subtype and is a complex trait with multigenic inheritance. Genome-wide association studies have previously identified a significant association between POAG and the SIX6 locus (rs10483727, odds ratio (OR) = 1.32, p = 3.87×10(-11)). SIX6 plays a role in ocular development and has been associated with the morphology of the optic nerve. We sequenced the SIX6 coding and regulatory regions in 262 POAG cases and 256 controls and identified six nonsynonymous coding variants, including five rare and one common variant, Asn141His (rs33912345), which was associated significantly with POAG (OR = 1.27, p = 4.2×10(-10)) in the NEIGHBOR/GLAUGEN datasets. These variants were tested in an in vivo Danio rerio (zebrafish) complementation assay to evaluate ocular metrics such as eye size and optic nerve structure. Five variants, found primarily in POAG cases, were hypomorphic or null, while the sixth variant, found only in controls, was benign. One variant in the SIX6 enhancer increased expression of SIX6 and disrupted its regulation. Finally, to our knowledge for the first time, we have identified a clinical feature in POAG patients that appears to be dependent upon SIX6 genotype: patients who are homozygous for the SIX6 risk allele (His141) have a statistically thinner retinal nerve fiber layer than patients homozygous for the SIX6 non-risk allele (Asn141). Our results, in combination with previous SIX6 work, lead us to hypothesize that SIX6 risk variants disrupt the development of the neural retina, leading to a reduced number of retinal ganglion cells, thereby increasing the risk of glaucoma-associated vision loss.

The lamina cribrosa (LC) is a layer of fenestrated connective tissue tethered to the posterior sclera across the scleral canal in the optic nerve head (ONH). It is located at the interface of intracranial and intraocular compartments and is exposed to intraocular pressure (IOP) anteriorly and intracranial pressure (ICP) or Cerebrospinal fluid (CSF) pressure (CSFP) posteriorly. We hypothesize that the pressure difference across LC will determine LC position and meridional diameter of scleral canal (also called Bruch's membrane opening diameter; BMOD). We enrolled 19 human subjects undergoing a medically necessary lumbar puncture (LP) to lower CSFP and 6 anesthetized pigs, whose ICP was increased in 5 mm Hg increments using a lumbar catheter. We imaged ONH using optical coherence tomography and measured IOP and CSFP/ICP at baseline and after each intervention. Radial tomographic ONH scans were analyzed by two independent graders using ImageJ, an open-source software. The following ONH morphological parameters were obtained: BMOD, anterior LC depth and retinal thickness. We modeled effects of acute CSFP/ICP changes on ONH morphological parameters using ANOVA (human study) and generalized linear model (pig study). For 19 human subjects, CSFP ranged from 5 to 42 mm Hg before LP and 2 to 19.4 mm Hg after LP. For the six pigs, baseline ICP ranged from 1.5 to 9 mm Hg and maximum stable ICP ranged from 18 to 40 mm Hg. Our models showed that acute CSFP/ICP changes had no significant effect on ONH morphological parameters in both humans and pigs. We conclude that ONH does not show measurable morphological changes in response to acute changes of CSFP/ICP. Proposed mechanisms include compensatory and opposing changes in IOP and CSFP/ICP and nonlinear or nonmonotonic effects of IOP and CSFP/ICP across LC. [ABSTRACT FROM AUTHOR]

Orbital veins such as the retinal veins and episcleral veins drain into the cavernous sinus, an intracranial venous structure. We studied the effects of acute intracranial pressure (ICP) elevation on episcleral venous pressure, intraocular pressure and retinal vein diameter in an established non-survival pig model. In six adult female domestic pigs, we increased ICP in 5 mm Hg increments using saline infusion through a lumbar drain. We measured ICP (using parenchymal pressure monitor), intraocular pressure (using pneumatonometer), episcleral venous pressure (using venomanometer), retinal vein diameter (using OCT images) and arterial blood pressure at each stable ICP increment. The average baseline ICP was 5.4 mm Hg (range 1.5–9 mm Hg) and the maximum stable ICP ranged from 18 to 40 mm Hg. Linear mixed models with random intercepts were used to evaluate the effect of acute ICP increase on outcome variables. With acute ICP elevation, we found loss of retinal venous pulsation and increased episcleral venous pressure, intraocular pressure and retinal vein pressure in all animals. Specifically, acute ICP increase was significantly associated with episcleral venous pressure (β = 0.31; 95% CI 0.14–0.48, p <.001), intraocular pressure (β = 0.37, 95%CI 0.24–0.50; p <.001) and retinal vein diameter (β = 11.29, 95%CI 1.57–21.00; p =.03) after controlling for the effects of arterial blood pressure. We believe that the ophthalmic effects of acute ICP elevation are mediated by increased intracranial venous pressure producing upstream pressure changes within the orbital and retinal veins. These results offer exciting possibilities for the development of non-invasive ophthalmic biomarkers to estimate acute ICP elevations following significant neuro-trauma. [ABSTRACT FROM AUTHOR]

Purpose/Aim of the study: Measured intraocular pressure (IOP) after corneal incisions may not be reflective of the true IOP because of changes in corneal biomechanical properties. The purpose of this study is to investigate the effect of various corneal incisions on pneumotonometer accuracy in enucleated porcine eyes. Materials and Methods: A pneumotonometer was used to measure IOP (IOPp) at manometrically controlled pressure levels of 10, 20, 30 and 40 mmHg in enucleated porcine eyes. IOP measurements at each level were repeated after one of the following corneal incisions: radial keratotomy (8 eyes), lamellar dissection (10 eyes), clear cornea standard phacoemulsification incisions (10 eyes). The pneumotonometer error, defined as the difference between IOPp and manometric pressure (IOPm), was calculated for each pressure level. The error before the corneal incisions was compared to the error after the corneal incisions to assess the accuracy of the pneumotonometer. Results: The pneumotonometer underestimates true IOP at all pressure levels, both before and after the corneal procedures. There was a statistically significant greater underestimation of IOP after radial keratotomy incisions at pressure levels of 20, 30 and 40 mmHg (p =.013, 0.004, and 0.002, respectively). There was no statistically significant difference in the amount of pneumotonometer underestimation error after lamellar dissection or standard cataract incisions. Conclusion: The pneumotonometer underestimates true IOP in enucleated porcine eyes at all pressure levels between 10–40 mmHg. Radial keratotomy incisions caused a statistically significant greater underestimation error in pneumotonometry measurements at pressures of 20–40 mmHg. Lamellar dissection and clear corneal cataract incisions did not cause an additional error in pneumotonometry measurements in enucleated porcine eyes. [ABSTRACT FROM AUTHOR]

Background Glaucoma prevalence and subtype profile vary across different racial and ethnic groups. This study provides a comparative evaluation of differences in aqueous humour dynamics (AHD) and ocular biometrics in healthy Chinese and Caucasian adults of two different age groups. Methods Data from two independent studies with identical designs were compared. Cohorts included young adults (20-30 years old, 32 Chinese and 39 Caucasians) and older adults (>50 years old, 37 Chinese and 46 Caucasians). Parameters of AHD and ocular biometrics were evaluated. Group comparisons were made by generalised estimating equation methods. results Differences in young adult Caucasians compared with similarly aged Chinese were thinner central cornea (-29.27 µm, p<0.001), lower intraocular pressure (IOP) (-2.33 mm Hg, p<0.001), larger anterior chamber volume (ACV) (28.78 µL, p<0.001) and faster uveoscleral outflow rate (Fu) (0.82 µL/min, p<0.001). Differences in older adult Caucasians compared with similarly aged Chinese were slower aqueous flow rate (Fa) (-0.28 µL/min, p=0.042), lower IOP (-1.97 mm Hg, p<0.001) and larger ACV (33.15 µL, p<0.001). Considering all subjects together by race, Caucasian subjects had slower Fa (-0.22 µL/min, p=0.035), thinner corneas (-0.52 µm, p=0.003), lower IOP (-2.11 mm Hg, p<0.001), higher ACV (30.39 µL, p<0.001) and faster Fu (0.63 µL/min, p<0.001). Conclusion Differences in AHD and biometrics between Caucasian and Chinese adults include larger ACVs which may contribute to the wider angles reported in Caucasians, and slower Fa rates coupled with faster Fu rates which may contribute to their lower IOP and lower overall risk of glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: To report a case of uveitis-glaucoma-hyphema syndrome (UGHS) secondary to a large capsulorhexis with an intracaspular intraocular lens (IOL) managed with IOL exchange and gonioscopy assisted transluminal trabeculotomy (GATT). Case Report: A 73-year-old male patient presented with UGHS of the right eye in the setting of an intracapsular single-piece acrylic IOL with circumferential optic and partial haptics exposure due to a large capsulorhexis. In lieu of the patient's uncomplicated surgical history, subtle symptoms, and clinical findings, the diagnosis and referral was delayed until intraocular pressure reached a peak of 50 mmHg with recurrent anterior chamber cells. The patient underwent combined IOL exchange with placement of a 3-piece sulcus IOL and GATT, which finally resolved the UGHS. Conclusion: With respect to the increasing prevalence of intracapsular single-piece IOL implantation, it is important to recognize UGHS and thus fashion proper sized capsulorhexis to prevent this vision threatening complication. GATT may be considered to be one of the glaucoma surgeries combined with the IOL surgical procedures in UGHS. [ABSTRACT FROM AUTHOR]

Purpose: The Water-Drinking Test (WDT) has been shown to predict the diurnal IOP change. This study evaluates the factors that may affect the WDT results.Methods: This study was conducted on 203 glaucoma patients who had undergone trabeculectomy (53) or tube surgery (31), or had a medically controlled open-angle (82) or closed-angle (37) glaucoma. IOP was measured at baseline and then every 15 minutes over a one-hour period after drinking water. The main outcome measures were IOP change (increase in IOP from baseline) at all measurement time points, IOP peak (highest IOP after drinking water), IOP fluctuation (difference between IOP peak and baseline), and assessing the association of these IOPs with a patient's demographic and management modalities.Results: The mean age of the participants was 54±18 years, and 113 (56%) were male. Female patients showed greater IOP fluctuation than males (7.28 vs. 5.92 mm Hg; P=0.016), and a greater IOP peak (22.7 vs. 20.1 mm Hg; P=0.001). The observed associations between gender and IOP changes were only significant in <50 years. IOP at 60 minutes was greater in tube than trabeculectomy (5.6 vs. 3.1 mm Hg; P=0.007). The number of topical medications showed a direct independent association with IOP changes (P<0.001). Compared to other classes of topical medications, latanoprost showed lower WDT-IOP profile (P=0.0003).Conclusions: WDT-IOP change was diminished in subjects on latanoprost, and was greater in females <50 years, and those on greater number of medications. [ABSTRACT FROM AUTHOR]

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.

The article describes the case of a 70-year-old male patient with Listeria monocytogenes-related endophthalmitis that progressed to panophthalmitis. The patient initially complained of decreased vision in his right eye despite administration of prednisolone acetate. Results of visual acuity and intraocular pressure examinations are reported. The treatments given include intravenous vancomycin and meropenem and therapeutic enucleation with iodoform.