The ability of healthy volunteers to simulate a neurologic field defect on automated perimetry.

OBJECTIVE: To determine if volunteers can simulate and reproduce 3 types of neurologic field defects: hemianopia, quadrantanopia, and central scotoma. DESIGN: Cross-sectional study. PARTICIPANTS: Thirty healthy volunteers new to perimetry (including automated perimetry). METHODS: After informed consent, volunteers were randomized to 1 of the 3 visual field defects listed above. All visual field testing was performed on the right eye using the Humphrey Field Analyzer (HFA; Carl Zeiss Meditec, Dublin, CA) SITA Fast 24-2 protocol. Each volunteer was provided with standard new patient instructions and was shown a diagram of the defect to be simulated. Two sets of visual fields were performed on the right eye with 10 minutes between tests. Three experts used the Ocular Hypertension Treatment Study reading center criteria and determined if the simulation was successful. MAIN OUTCOME MEASURES: Proportion of volunteers able to simulate the assigned visual field. RESULTS: All 10 volunteers (100%) successfully simulated a hemianopia on the first and second fields. All 10 volunteers (100%) simulated a quadrantanopia on the first field and 9 (90%) did so on the second field. Eight volunteers (80%) successfully simulated a central scotoma in the first field and all 10 (100%) did so on in the second field. Reliability criteria were excellent. Forty-seven fields (78%) had 0 fixation losses, 48 (80%) had 0 false-positive results, and 44 (73%) had 0 false-negative results. CONCLUSIONS: It is easy to simulate reproducible and reliable neurologic field defects on automated perimetry using HFA.

Withaferin A effectively targets soluble vimentin in the glaucoma filtration surgical model of fibrosis.

Withaferin A (WFA) is a natural product that binds to soluble forms of the type III intermediate filament (IF) vimentin. Currently, it is unknown under what pathophysiological contexts vimentin is druggable, as cytoskeltal vimentin-IFs are abundantly expressed. To investigate druggability of vimentin, we exploited rabbit Tenon's capsule fibroblast (RbTCF) cell cultures and the rabbit glaucoma filtration surgical (GFS) model of fibrosis. WFA potently caused G0/G1 cell cycle inhibition (IC50 25 nM) in RbTCFs, downregulating ubiquitin E3 ligase skp2 and inducing p27(Kip1) expression. Transforming growth factor (TGF)-ß-induced myofibroblast transformation caused development of cell spheroids with numerous elongated invadopodia, which WFA blocked potently by downregulating soluble vimentin and α-smooth muscle actin (SMA) expression. In the pilot proof-of-concept study using the GFS model, subconjunctival injections of a low WFA dose reduced skp2 expression in Tenon's capsule and increased p27(Kip1) expression without significant alteration to vimentin-IFs. This treatment maintains significant nanomolar WFA concentrations in anterior segment tissues that correspond to WFA's cell cycle targeting activity. A ten-fold higher WFA dose caused potent downregulation of soluble vimentin and skp2 expression, but as found in cell cultures, no further increase in p27(Kip1) expression was observed. Instead, this high WFA dose potently induced vimentin-IF disruption and downregulated α-SMA expression that mimicked WFA activity in TGF-ß-treated RbTCFs that blocked cell contractile activity at submicromolar concentrations. These findings illuminate that localized WFA injection to ocular tissues exerts pharmacological control over the skp2-p27(Kip1) pathway by targeting of soluble vimentin in a model of surgical fibrosis.

Repeatability and reproducibility of Goldmann applanation, dynamic contour, and ocular response analyzer tonometry.

PURPOSE: To evaluate the repeatability and interoperator reproducibility of the Pascal dynamic contour tonometry (DCT), ocular response analyzer (ORA), and Goldmann applanation tonometer (GAT) in a single population of normal individuals. METHODS: The study included 52 eyes from 26 normal individuals. One operator measured the intraocular pressure (IOP) with each tonometer 3 times while 2 additional operators each measured the IOP with each tonometer once. Repeatability and reproducibility were assessed by the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Agreement among tonometers was also assessed using Bland-Altman plots. RESULTS: The mean age of included participants was 31.5±8.8 years and 15 (58%) were female individuals. In general, both intraoperator repeatability and interoperator reproducibility were significantly higher for DCT compared with the other tonometers. Intraoperator DCT (CV=3.7, ICC=0.89), GAT (CV=9.7, ICC=0.79), IOPg (CV=7.0, ICC=0.79), and IOPcc (CV=9.8, ICC=0.57). Interoperator DCT (CV=6.1, ICC=0.73), GAT (CV=9.0, ICC=0.82), and IOPg (CV=10.8, ICC=0.63), IOPcc (CV=11.7, ICC=0.49). CONCLUSION: Overall, DCT was significantly more repeatable and reproducible than GAT, IOPg and IOPcc. The better reproducibility of the DCT may result in more precise measurements for monitoring IOP changes over time compared to GAT and ORA.

Evaluation of extended release brimonidine intravitreal device in normotensive rabbit eyes.

PURPOSE: To evaluate the safety profile of a brimonidine extended release intravitreal implant, in normotensive rabbit eyes. METHODS: Devices were made from hollow poly-l-lactic acid (PLA) tubes and contained hundred micrograms of brimonidine pamoate. Device was injected intravitreally in one eye of 12 New Zealand pigmented rabbits, whereas other eye was injected with a sham implant in masked fashion. Ocular examination was conducted at baseline and months 1, 3 and 6 including dilated fundus examination and electro-retinogram (ERG). Four rabbits were sacrificed at each time-point for retinal histology. ERG data were compared between groups and time-points using anova. RESULTS: No complications were reported from either eye of any rabbits over a 6-month period. Photopic A wave was reduced in the control eye at 1 month compared with baseline (p < 0.01). There was no significant difference in other ERG parameters between the groups at different time-points. Gross retinal histology was normal at all time-points. CONCLUSION: Extended release intravitreal brimonidine device was found to be safe and in normotensive rabbit eyes.

Comparison of unenhanced and enhanced imaging protocols for angle measurements with anterior segment optical coherence tomography.

BACKGROUND AND OBJECTIVE: To compare the intraobserver and interobserver agreement of anterior chamber angle measurements using unenhanced and enhanced imaging protocols for anterior segment optical coherence tomography (AS-OCT). PATIENTS AND METHODS: Anterior segments of 30 eyes of 15 healthy subjects (mean age: 33.8 ± 13.0 years, 8 women) were imaged by a single examiner with AS-OCT using unenhanced and enhanced imaging protocol. Two masked observers analyzed each image independently on two separate occasions. The reproducibility of angle parameters was estimated by calculating coefficients of variation separately for each observer. Bland-Altman plots were constructed to assess the intraobserver and interobserver agreement. RESULTS: The intraobserver and interobserver reproducibility was similar between imaging protocols. Intra-observer and interobserver agreements were also similar for all parameters evaluated. The best estimate of scleral spur location was determined in all images by both observers. CONCLUSION: Measurement variability was similar with the unenhanced and enhanced imaging protocol in this series of eyes with open angles.

Association of visual field severity and parapapillary retinal blood flow in open-angle glaucoma.

PURPOSE: To examine the association of the parapapillary blood flow parameters with severity of visual field loss (VFL) in open-angle glaucoma (OAG) patients. DESIGN: Observational clinical study. METHODS: Fifty-two patients with OAG and 30 normal subjects were studied prospectively. Parapapillary blood flow parameters were obtained for superotemporal and inferotemporal quadrants using the scanning laser Doppler flowmeter. Mean deviation score was used to determine the severity of VFL both as continuous variable and stratified by severity: no VFL (OAG A) 6 dB. In the OAG patients with an abnormal Glaucoma Hemifield Test, the hemifield with a predominant VFL was determined. Linear regression analysis and analysis of covariance were used to assess the relationship between the severity of the VFL and the parapapillary blood flow parameters. The variance in mean parapapillary blood flow was assessed using standard deviation (SD) and coefficient of variation (COV). RESULTS: There was no correlation between the severity of VFL and parapapillary blood flow parameters. Variance in the mean parapapillary blood flow was significantly greater in OAG patients with VFL compared with OAG patients without VFL and normal subjects for the superotemporal quadrant (SD, P=0.04; COV, P=0.02) and the inferotemporal quadrant (SD, P<0.02; COV, P=0.02). Results for COV were confirmed for the inferotemporal quadrant in analysis of covariance after adjusting for age and intraocular pressure (F=1.60, P=0.04). CONCLUSION: The parapapillary blood flow did not correlate with VFL. However, the variance in meanparapapillary blood flow was significantly larger in OAG patients with VFL, thus suggesting vascular abnormality.

Correlation among choroidal, parapapillary, and retrobulbar vascular parameters in glaucoma.

PURPOSE: To study and compare the correlation among choroidal, parapapillary, and retrobulbar vascular parameters in healthy subjects, glaucoma suspects, and open-angle glaucoma (OAG) patients. DESIGN: Prospective observational clinical study. METHODS: The study included one randomly selected eye from 21 normal subjects, 30 glaucoma suspects based on optic disc appearance, and 22 OAG patients. The pulsatile ocular blood flow (POBF), a measure of choroidal blood flow, was assessed using ocular blood flow analyzer whereas parapapillary blood flow and blood velocity of retrobulbar blood vessels were measured using scanning laser Doppler flowmetry and color Doppler imaging, respectively. All vascular parameters along with blood pressure and intraocular pressure measurements were obtained within a 2-hour period. Univariate regression analyses were used to evaluate the correlation of POBF values with parapapillary blood flow values, retrobulbar blood flow velocities, and resistive index, which represents vascular resistance, in each group. Two multiple linear regression models were created based on results of univariate analyses and included POBF, mean parapapillary blood flow, age, and mean ocular perfusion pressure; and POBF, temporal short posterior ciliary artery resistive index, age, and mean ocular perfusion pressure. RESULTS: POBF was significantly associated with parapapillary blood flow (r2 = 0.54; P < .001, positive correlation) and temporal short posterior ciliary artery resistive index (r2 = 0.39; P < .001, negative correlation) in normal subjects. Results were consistent when corrected for age, intraocular pressure, and blood pressure parameters. POBF values did not correlate with parapapillary blood flow values or temporal short posterior ciliary artery resistive index in glaucoma suspects or OAG patients. CONCLUSION: The relationships of POBF with parapapillary blood flow and calculated retrobulbar vascular resistance differs among normal subjects, glaucoma suspects, and OAG patients. This provides further evidence of vascular dysregulation in OAG.

Relationship of the 24-hour pattern of intraocular pressure with optic disc appearance in primary open-angle glaucoma.

PURPOSE: To study the relationship between the 24-hour pattern of intraocular pressure (IOP) with optic disc appearance in primary open-angle glaucoma (POAG) patients. DESIGN: Observational clinical study. PARTICIPANTS: Seventy-five eyes of 45 POAG patients. METHODS: Patients underwent 24-hour IOP assessment in a sleep laboratory. Two observers classified the optic disc appearance for each eye as either concentric or nonconcentric. The IOP measurements were obtained with the subjects in the supine and sitting positions during the diurnal period and in the supine position during the nocturnal period. The mean, peak, and trough IOP and IOP range (peak through trough) were calculated for the office-hour period (9 am to 4 pm), the diurnal period (7 am to 11 pm), the nocturnal period (11 pm to 7 am), and the 24-hour period. Further, the difference in supine and sitting IOP during the diurnal periods was calculated, and generalized estimating equations were used to compare IOP measurements in both groups. MAIN OUTCOME MEASURES: Diurnal and nocturnal IOP measurements. RESULTS: Forty eyes were classified as having concentric optic disc appearance and 35 eyes as having nonconcentric optic disc appearance. The mean nocturnal IOP was significantly greater in the concentric group (mean+/-standard deviation [SD], 24.0+/-3.8 mmHg) compared with the nonconcentric group (mean+/-SD, 21.9+/-1.9 mmHg; P = 0.004). Most IOP peaks of patients with the concentric optic disc appearance occurred during the nocturnal period, as opposed to the diurnal period of patients with the nonconcentric optic disc appearance. CONCLUSIONS: Concentric optic disc appearance may be associated with higher nocturnal IOP compared with nonconcentric optic disc appearance. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Relationships among systemic blood pressure, intraocular pressure, and open-angle glaucoma.

Several vascular factors, including systemic hypertension (or high blood pressure [HBP]), ocular perfusion pressure, and nocturnal hypotension, have been identified as risk factors for the development and progression of glaucoma. The results of epidemiologic studies of these factors and their relationships to intraocular pressure (IOP) and open-angle glaucoma (OAG) have been contradictory. Inconsistent definitions of HBP and OAG, inconsistent design, and differing population characteristics within these studies have obfuscated definitive conclusions. Here, we review the relationships among blood pressure, IOP, and OAG.

Long-term results of Molteno implant insertion in cases of chronic angle closure glaucoma.

BACKGROUND: This study was undertaken to provide data on the long-term results of cases of chronic angle closure glaucoma with additional risk factors treated by Molteno implants between 1985 and 2004 at Dunedin Hospital, New Zealand. METHODS: A prospective non-comparative case series followed 21 eyes (17 patients) for a mean of 5.7 years (range 1.3-16.3 years) in terms of intraocular pressure, visual acuity and subsequent procedures. RESULTS: Insertion of a Molteno implant has controlled the intraocular pressure at 21 mmHg or less in 100% of cases at 5 years after surgery, the probability of control being 0.95 (95% CI 0.91-0.99). The mean number of hypotensive medications reduced from 2.04 (SD 0.92) preoperatively to 1.40, 0.64 and 0.66 at 1, 2 and 5 years, respectively. The mean visual acuity improved from 6/18 preoperatively to 6/12 at 1 year and declined to 6/13.5 at 2 and 5 years. CONCLUSION: Insertion of Molteno implants was a safe and effective procedure in the management of complex cases of chronic angle closure glaucoma.

The effect of phacoemulsification cataract surgery on the measurement of retinal nerve fiber layer thickness using optical coherence tomography.

PURPOSE: To evaluate whether the measurement of retinal nerve fiber layer (RNFL) thickness using optical coherence tomography (OCT) changes after cataract surgery. METHODS: This prospective, randomized, observational, cross-sectional clinical study included 24 eyes of 24 patients who underwent phacoemusification with implant. All patients had no preexisting retinal or optic nerve pathology or other media opacities that might influence the RNFL thickness. The classification and the grading of cataract were based on the Lens Opacities Classification System III (LOCS III). All eyes were scanned immediately before cataract surgery with OCT using Fast RNFL program. All eyes had circular scans around the optic disk with a diameter of 3.4 mm. The OCT was repeated 4 weeks after surgery when the patients returned for postoperative check using the same programme. RESULTS: The mean preoperative RNFL thickness was 84.9 +/- 16.5. The postoperative mean RNFL thickness was 93.0 +/- 17.6. The pre-and postoperative values of the mean RNFL and signal/noise ratio (SNR) are statistically significant (P < 0.05). CONCLUSIONS: Lens opacities may affect the image quality of OCT scans used to measure RNFL thickness as indicated by preoperative low SNR. Cataract extraction results in an apparent increase of the RNFL thickness.

Neodymium:YAG laser anterior capsulotomy for capsular contraction syndrome.

BACKGROUND AND OBJECTIVE: This study presents the outcome of neodymium:YAG laser anterior capsulotomy for capsular contraction syndrome, the safety profile and effectiveness of which are unclear. PATIENTS AND METHODS: Records of 32 patients with a minimum of 3 months of follow-up were reviewed retrospectively. The procedure was considered successful if all of the following criteria were met: centered intraocular lens (IOL) or no obvious change in IOL centration post-capsulotomy, no evidence of re-phimosis in the follow-up period; and no further requirement for surgical intervention due to capsular contraction syndrome in the follow-up period or complications were recorded. RESULTS: The procedure was successful in 25 case; (78%). Failed cases (n = 7, 22.0%) included 5 cases of re-phimosis and 2 cases with progressive IOL decentration. The failure rate was higher in cases with preoperative IOL decentration (P< .01). CONCLUSION: Neodymium:YAG laser anterior capsulotomy was successful in the majority of cases. The failure rate was higher with preoperative IOL decentration.

Deep intramuscular methylprednisolone treatment of recurrent scleritis.

PURPOSE: To evaluate the efficacy of deep intramuscular methylprednisolone (IMMP) in the treatment of recurrent scleritis. METHODS: A total of 15 patients with scleritis (12 anterior, 3 pan) underwent IMMP injection deep into the thigh. Thirteen patients were already being treated with oral non-steroidal anti-inflammatory drugs, oral prednisolone, an oral immunosuppressive agent, or a combination of these drugs. A second IMMP injection was given to nine patients, making a total of 24 injections. Follow-up ranged from 4 to 18 months. RESULTS: There was a documented improvement in scleritis after 21/24 (87.3%) injections with a mean duration of improvement of 5.7 months. No patient required the introduction of oral corticosteroid or immunosuppressive agent, and only one patient required an increase in methotrexate to control the disease. No systemic, injection site, or ocular side effects were noted. CONCLUSIONS: Deep IMMP is a safe and effective treatment for scleritis. It ensures compliance, avoids the systemic side effects of oral corticosteroids, and is easily repeatable in the outpatient setting.

Chronic open angle glaucoma: patient awareness of the nature of the disease, topical medication, compliance and the prevalence of systemic symptoms.

PURPOSE: To study the awareness of the nature of the disease, compliance with treatment, and prevalence of systemic symptoms in a group of patients with chronic open angle glaucoma (COAG). METHOD: A structured questionnaire was designed and given to 260 consecutive COAG patients attending a general ophthalmology clinic. Questions related to the increased risk of COAG amongst family members, screening of family members, nature of field defects, variation in IOP, topical treatment and availability of a free eye test for a COAG patient in the UK were asked. Compliance and systemic symptoms were also assessed. RESULTS: Forty-one per cent (107 of 260) of patients in the study group were aware of the increased risk of COAG in family members and 45.5% (118 of 260) of patient's family members had undergone screening for COAG. Seventy-three per cent (191 of 260) of the patients were aware of their own and their family members' entitlement to a free eye test. Seventy-seven per cent of patients claimed full compliance. Thirty per cent of patients were noted to have systemic symptoms. CONCLUSIONS: The awareness of the nature of COAG in this population was low and incidence of perceived drug related systemic symptoms very high. Both of these may contribute to poor compliance.