Angelo P. Tanna

Diagnosis of glaucoma and detection of glaucoma progression using spectral domain optical coherence tomography.

Purpose of review With the rapid adoption of spectral domain optical coherence tomography (SDOCT) in clinical practice and the recent advances in software technology, there is a need for a review of the literature on glaucoma detection and progression analysis algorithms designed for the commercially available instruments. Recent findings Peripapillary retinal nerve fiber layer (RNFL) thickness and macular thickness, including segmental macular thickness calculation algorithms, have been demonstrated to be repeatable and reproducible, and have a high degree of diagnostic sensitivity and specificity in discriminating between healthy and glaucomatous eyes across the glaucoma continuum. Newer software capabilities such as glaucoma progression detection algorithms provide an objective analysis of longitudinally obtained structural data that enhances our ability to detect glaucomatous progression. RNFL measurements obtained with SDOCT appear more sensitive than time domain OCT (TDOCT) for glaucoma progression detection; however, agreement with the assessments of visual field progression is poor. Summary Over the last few years, several studies have been performed to assess the diagnostic performance of SDOCT structural imaging and its validity in assessing glaucoma progression. Most evidence suggests that SDOCT performs similarly to TDOCT for glaucoma diagnosis; however, SDOCT may be superior for the detection of early stage disease. With respect to progression detection, SDOCT represents an important technological advance because of its improved resolution and repeatability. Advancements in RNFL thickness quantification, segmental macular thickness calculation and progression detection algorithms, when used correctly, may help to improve our ability to diagnose and manage glaucoma.

Incidence and management of cataract after retinal detachment repair with silicone oil in immune compromised patients with cytomegalovirus retinitis.

PURPOSE To determine the incidence of and risk factors for cataract and to describe the visual outcomes of cataract surgery in eyes with cytomegalovirus-related retinal detachments repaired with silicone oil. STUDY DESIGN Retrospective cohort study. METHODS A prospectively generated database of all patients with cytomegalovirus retinitis examined at a single tertiary care institution was used to identify all cases of retinal detachment between October 1983 and August 1997. Data on retinal detachment repair, development of cataract, and outcomes of cataract surgery were obtained retrospectively. RESULTS Among 904 eyes of 587 immune-compromised patients diagnosed with cytomegalovirus retinitis, 198 eyes of 155 patients developed retinal detachment. Among these, 106 eyes of 90 patients underwent retinal detachment repair with silicone oil. The Kaplan-Meier estimated median time to cataract was 1.8 months after surgery with silicone oil. The adjusted relative risk of cataract in eyes that underwent retinal detachment repair with silicone oil compared with eyes that did not was 6.74 (P <.0001). Eight of the eyes that developed cataract underwent uncomplicated cataract surgery by phacoemulsification and posterior chamber intraocular lens implantation. Among these, six eyes experienced >or=2 lines of improvement in visual acuity. All developed posterior capsule opacification a median of 7 days after cataract surgery. Four of five eyes that that underwent neodymium:yttrium-aluminum-garnet laser capsulotomy experienced >or=2 lines improvement in visual acuity. CONCLUSIONS There is a high incidence of cataract after surgery with silicone oil tamponade for cytomegalovirus-related retinal detachment. Posterior capsule opacification occurs rapidly after cataract surgery in these patients.

Meta-analysis of the Efficacy and Safety of α2-Adrenergic Agonists, β-Adrenergic Antagonists, and Topical Carbonic Anhydrase Inhibitors With Prostaglandin Analogs

OBJECTIVE To perform a meta-analysis to estimate the intraocular pressure (IOP)-lowering efficacy and safety of alpha(2)-adrenergic agonists (AAs), beta-adrenergic antagonists (BBs), and topical carbonic anhydrase inhibitors (TCAIs) when used in combination with a prostaglandin analog (PGA). METHODS MEDLINE, Embase, and the Cochrane Controlled Trials Register were systematically searched for relevant articles in April 2009. Ten observer-masked randomized clinical trials that reported baseline IOP while receiving PGA monotherapy and follow-up IOP while receiving combination therapy were identified. The pooled IOP-lowering efficacy achieved with each class of adjunctive agent was calculated using random-effects models. The frequencies of adverse events were pooled across studies and compared using Fisher exact test. RESULTS Mean diurnal IOP reduction achieved in all 3 groups was statistically similar (P = .22). At trough, IOP reduction was greater in the TCAI (P < .001) and BB (P < .001) groups than in the AA group. Peak IOP reduction was similar in the 3 groups (P = .66). Eye or eyelid pain or burning and xerostomia were significantly more common in the AA group. Fatigue, weakness, or dizziness was more common in the AA and BB groups compared with the TCAI group. Taste disturbance was significantly more common in the TCAI group. CONCLUSIONS All 3 classes are similarly effective in lowering mean diurnal IOP when used in combination with PGAs. The AA class is statistically significantly less effective in reducing IOP at trough compared with BBs and TCAIs. The types of adverse events that were identified varied among the different classes of adjunctive therapies.

Glaucoma Progression Analysis Software Compared with Expert Consensus Opinion in the Detection of Visual Field Progression in Glaucoma

PURPOSE To compare the results of Glaucoma Progression Analysis (GPA, Carl Zeiss Meditec, Dublin, CA) to subjective expert consensus in the detection of glaucomatous visual field progression. DESIGN Retrospective, observational case series. PARTICIPANTS We included 100 eyes of 83 glaucoma patients. METHODS Five serial Humphrey visual fields from 100 eyes of 83 glaucoma patients were evaluated by 5 masked glaucoma subspecialists for determination of progression. Four months later, with a randomly reordered patient sequence, the same visual field series were reevaluated by the same graders, at which time they had access to the Glaucoma Progression Analysis (GPA) printout. MAIN OUTCOME MEASURES The level of agreement between majority expert consensus and GPA, both before and after access to GPA data, was assessed using kappa statistics. RESULTS On initial review and on reevaluation with access to the GPA printout, the level of agreement between majority expert consensus and GPA was fair (kappa = 0.52, 95% confidence interval [CI], 0.35-0.69 and kappa = 0.62; 95% CI, 0.46-0.78, respectively). Expert consensus was more likely to classify a series of fields as showing progression than was GPA (P ≤ 0.002). There was good agreement between expert consensus on initial review and reevaluation 4 months later (kappa = 0.77; 95% CI, 0.65-0.90). CONCLUSIONS The level of agreement between majority expert consensus of subjective determination of visual field progression and GPA is fair. In cases of disagreement with GPA, the expert consensus classification was usually progression. Access to the results of GPA did not significantly change the level of agreement between expert consensus and the GPA result; however, expert consensus did change in 11 of 100 cases.

Correlation between intereye difference in visual field mean deviation values and relative afferent pupillary response as measured by an automated pupillometer in subjects with glaucoma.

Purpose:To evaluate the effectiveness of a new binocular infrared computerized pupillometer in the quantitative measurement of the relative afferent pupillary response in patients with glaucoma by assessing the correlation of the intereye difference in visual function as measured by standard automated perimetry (SAP) with the intereye difference in the afferent pupillary response. Methods:Twenty-three patients with glaucoma underwent examination with a prototype, automated, binocular pupillometer. Correlation between the intereye difference in the afferent pupillary response and the intereye difference in mean deviation (MD) was explored. Results:Within 7 months of pupillography, all patients underwent SAP using the Humphrey Field Analyzer IIi, 24-2, Swedish Interactive Threshold Algorithm. The intereye differential pupillary response was 0.69±0.59 (log units, mean±SD). The intereye difference in MD was 5.67±5.29 dB (mean±SD). There was a strong correlation between the intereye difference in the afferent pupillary response and the intereye difference in MD (Spearman correlation coefficient, r=−0.77; P<0.001). Conclusions:A new, binocular computerized pupillometer provides an automated method for the quantitative assessment of the afferent pupillary response. The intereye asymmetry in the pupil response correlates strongly with asymmetry in visual function, as measured by SAP, in patients with glaucoma.

Thermal Stability of Bimatoprost, Latanoprost, and Travoprost Under Simulated Daily Use

PURPOSE To determine the stability of bimatoprost, latanoprost, and travoprost under conditions of simulated daily use and varying degrees of thermal stress. METHODS Commercially available bimatoprost, latanoprost, and travoprost were obtained in their original bottles as distributed by the manufacturers. Bottles were stored in calibrated, nonhumidified, light-free incubators maintained at 27°C, 37°C, or 50°C for 3, 9, 15, or 30 days. Capped bottles were inverted and left uncapped for 1  min daily to simulate patient use; no drops were expelled. Bimatoprost concentration was analyzed using liquid chromatography with ultraviolet detection at 210  nm. Latanoprost and travoprost concentrations were analyzed by liquid chromatography/tandem mass spectrometry (MS/MS) using selected reaction monitoring. RESULTS Off-the-shelf control bottles of bimatoprost contained 102% of the labeled concentration. In all combinations of stress temperature and duration, mean bimatoprost concentration ranged from 100% to 116% of the labeled concentration with no measurable degradation. Off-the-shelf control bottles of latanoprost contained 115% of the labeled concentration. Mean latanoprost concentration ranged from 97% to 120% of the labeled concentration. Latanoprost was stable at 27°C. When stressed at 37°C or 50°C, latanoprost degraded at a rate of 0.15 or 0.29  μg/mL/day, respectively. Off-the-shelf control bottles of travoprost contained 120% of the labeled concentration. Mean travoprost concentration ranged from 83% to 142% of the labeled concentration. Travoprost was stable at 27°C and 37°C, although concentration measurements at 37°C exhibited high variability. When stressed at 50°C, travoprost degraded at a rate of 0.46  μg/mL/day. CONCLUSIONS Higher than expected concentrations for stressed drug samples are likely a result of evaporation. Under the conditions of thermal stress tested in this study, bimatoprost remained stable for all conditions tested. Latanoprost degradation was measurable only in samples stressed at 37°C and 50°C, whereas travoprost degradation was statistically significant only in samples stressed at 50°C.

Effect of instrument orientation on the accuracy of intraocular pressure measurements in human cadaveric eyes: manometric evaluation of the model 30 classic Pneumatonometer and Tono-Pen XL.

PurposeTo determine the effects of probe orientation on the accuracy of intraocular pressure (IOP) measurements obtained with pneumatonometry (Model 30 Classic Pneumatonometer, Reichert Ophthalmic Instruments, Depew, NY) and with a handheld electronic tonometer (Tono-Pen XL, Reichert Ophthalmic Instruments, Depew, NY). Materials and MethodsSix enucleated human eyes were obtained fewer than 24 hours postmortem. IOP was maintained at 10, 20, and 30 mm Hg, sequentially, via liquid column manometry. At each IOP setpoint, the eyes were positioned to mimic a sitting, supine, and prone patient. Pneumatonometry was performed in the sitting and supine orientations. Tono-Pen measurements were performed in the sitting, supine, and prone orientations. Accuracy was analyzed using multifactor repeated measures analysis of variance, and one-sample t tests. ResultsAt all IOP setpoints, for both instruments, probe orientation had no significant effect on the IOP measurement (pneumatonometer P=0.58; Tono-Pen P=0.85). At all 3 setpoints (10, 20, and 30 mm Hg) the pneumatonometer overestimated IOP (P<0.0001; P<0.0001; P=0.005, respectively). The Tono-Pen overestimated IOP at the 10 mm Hg setpoint (P<0.0001), but underestimated IOP at the 20 and 30 mm Hg setpoints (P=0.03; P<0.0001, respectively). ConclusionsUnder experimental conditions, probe orientation had no significant effect on IOP measurements for either instrument, suggesting that both can be used without correction in the tested orientations. In enucleated human cadaveric eyes, the pneumatonometer overestimated IOP at all setpoints. The handheld electronic tonometer overestimated IOP at 10 mm Hg, but underestimated IOP at the higher setpoints. It is unknown if these findings are generalizable to human eyes in vivo.

Nailfold Capillary Abnormalities in Primary Open-Angle Glaucoma: A Multisite Study.

PURPOSE There is considerable evidence for systemic vascular dysfunction in primary open-angle glaucoma (POAG). We performed nailfold capillary video microscopy to observe directly the nature of nonocular microvasculature abnormalities in POAG. METHODS We enrolled 199 POAG patients and 124 control subjects from four sites. We used JH-1004 capillaroscopes to perform nailfold capillary video microscopy on the fourth and fifth digits of each subjects nondominant hand. Videos were evaluated for hemorrhages, dilated capillary loops > 50 μm, and avascular zones > 100 μm by graders masked to case status. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for POAG were obtained by means of logistic regression analyses that were applied to data from all cases and controls. Corresponding estimates of moderate or severe POAG versus mild POAG (based on the Hodapp-Anderson-Parrish scale) were obtained among cases only. RESULTS After controlling for demographic factors, family history of glaucoma, systemic diseases, and use of anticoagulation and antiplatelet therapy, for each 100 nailfold capillaries assessed, all types of microvascular abnormalities were significantly associated with POAG. Specifically, the presence of any dilated capillaries (OR = 2.9; 95% CI, 1.6-5.6), avascular zones (OR = 4.4; 95% CI, 1.7-11.3) and hemorrhages (OR = 12.2; 95% CI, 5.9-25.1) were associated with POAG. Among cases, the frequency of microvascular abnormalities was not associated with glaucoma severity (P ≥ 0.43). CONCLUSIONS These data provided support for nonocular capillary bed abnormalities in POAG. Comparable vascular abnormalities in the optic nerve may render it susceptible to glaucomatous damage.

Bilateral Angle Closure Following Use of a Weight Loss Combination Agent Containing Topiramate

Purpose:To report a unique case of topiramate-induced bilateral angle closure following ingestion of a recently introduced weight loss medication containing topiramate, and to describe its management. Methods:Case report of a 39-year-old, otherwise healthy woman who experienced decreased vision, bilateral acute angle closure, choroidal thickening as measured with enhanced depth optical coherence tomography imaging, bilateral suprachoroidal effusions, and induced myopia 1 week after starting a weight loss medication, Qysmia, composed of phentermine 3.75 mg and topiramate 23 mg. Treatment was initiated with high-dose intravenous methylprednisolone, intravenous mannitol, topical difluprednate ophthalmic emulsion, atropine sulfate, and the fixed combination of brimonidine and timolol. At the 2-week follow-up visit, vision, intraocular pressure, and angle anatomy had returned to normal and there was resolution of choroidal and ciliary body effusions on ultrasound biomicroscopy. Conclusions:Bilateral acute angle closure may develop after ingestion of weight loss drugs containing topiramate.

Trends in Self-reported Visual Impairment in the United States: 1984 to 2010

OBJECTIVE To explore trends in the prevalence of self-reported visual impairment in the noninstitutionalized adult US population during the 27-year period from 1984 to 2010. DESIGN Data obtained from the National Health Interview Survey (NHIS) and the Survey of Income and Program Participation (SIPP) were used to analyze trends in the prevalence of self-reported visual impairment in the United States. PARTICIPANTS Representative, population-based samples of between 45 000 and 92 000 adults (NHIS) and between 37 000 and 71 000 adults (SIPP) during each year of data collection. METHODS Survey results were age-adjusted to a standard (2010) population. Sampling weights were used throughout the analysis using strata and primary sampling unit variables provided in the public use datasets to appropriately take into account the complex design of the surveys. The statistical significance of trends was estimated by computing the difference in chi-squares of a fit to a linear trendline and a fit without a trend. MAIN OUTCOME MEASURES The trends and percent change in the prevalence of visual impairment from 1984 to 1996 and from 1997 to 2010 for NHIS and 1984 to 2010 for SIPP. RESULTS On the basis of NHIS data, the prevalence of activity-limiting visual impairment among persons aged ≥65 years declined by 51.7% (P < 0.001), from 3.5% in 1984 to 1.7% in 1996, and by 45.8% (P < 0.001), from 3.1% in 1997 to 1.7% in 2010. On the basis of SIPP data, the prevalence of functional visual impairment in the same age category declined by 58.3% (P < 0.001), from 23.3% in 1984 to 9.7% in 2010, whereas the prevalence of severe functional impairment declined by 47.1% (P < 0.001), from 5.1% to 2.7%. CONCLUSIONS There was a marked reduction in the prevalence of self-reported visual impairment in the noninstitutionalized adult US population during the period from 1984 to 2010.