Delan Jinapriya

Do Findings on Routine Examination Identify Patients at Risk for Primary Open-Angle Glaucoma?: The Rational Clinical Examination Systematic Review

IMPORTANCE Glaucoma is the second leading cause of blindness worldwide, and its insidious onset is often associated with diagnostic delay. Since glaucoma progression can often be effectively diminished when treated, identifying individuals at risk for glaucoma could potentially lead to earlier detection and prevent associated vision loss. OBJECTIVE To quantify the diagnostic accuracy of examination findings and relevant risk factors in identifying individuals with primary open-angle glaucoma (POAG), the most common form of glaucoma in North America. DATA SOURCES Structured Medline (January 1950-January 2013) search and a hand search of references and citations of retrieved articles yielding 57 articles from 41 studies. STUDY SELECTION Population-based studies of high-level methods relating relevant examination findings of cup-to-disc ratio (CDR), CDR asymmetry, intraocular pressure (IOP), and demographic risk factors to the presence of POAG. RESULTS The summary prevalence of glaucoma in the highest-quality studies was 2.6% (95% CI, 2.1%-3.1%). Among risk factors evaluated, high myopia (≥6 diopters; odds ratio [OR], 5.7; 95% CI, 3.1-11) and family history (OR, 3.3; 95% CI, 2.0-5.6) had the strongest association with glaucoma. Black race (OR, 2.9; 95% CI, 1.4-5.9) and increasing age (especially age >80 years; OR, 2.9; 95% CI, 1.9-4.3) were also associated with an increased risk. As CDR increased, the likelihood for POAG increased with a likelihood ratio (LR) of 14 (95% CI, 5.3-39) for CDR of 0.7 or greater. Increasing CDR asymmetry was also associated with an increased likelihood for POAG (CDR asymmetry ≥0.3; LR, 7.3; 95% CI, 3.3-16). No single threshold for CDR or asymmetry ruled out glaucoma. The presence of a disc hemorrhage (LR, 12; 95% CI, 2.9-48) was highly suggestive of glaucoma, but the absence of a hemorrhage was nondiagnostic (LR, 0.94; 95% CI, 0.83-0.98). At the commonly used cutoff for high IOP (≥22), the LR was 13 (95% CI, 8.2-17), while lower IOP made glaucoma less likely (LR, 0.65; 95% CI, 0.55-0.76). We found no studies of screening examinations performed by generalist physicians in a routine setting. CONCLUSIONS AND RELEVANCE Individual findings of increased CDR, CDR asymmetry, disc hemorrhage, and elevated IOP, as well as demographic risk factors of family history, black race, and advanced age are associated with increased risk for POAG, but their absence does not effectively rule out POAG. The best available data support examination by an ophthalmologist as the most accurate way to detect glaucoma.

Comparison of visual recovery following ex-PRESS versus trabeculectomy: results of a prospective randomized controlled trial.

Purpose:To compare the rate of visual recovery after Ex-PRESS implantation versus standard trabeculectomy. Patients and Methods:Subjects enrolled in a prospective randomized controlled trial comparing Ex-PRESS to trabeculectomy were analyzed for postoperative changes in visual acuity (VA). Risk factors for visual loss (split fixation, cup-disc ratio, intraocular pressure, visual field mean deviation, and hypotony) were evaluated. Results:Sixty-four subjects were enrolled (33 Ex-PRESS, 31 trabeculectomy). There was no significant difference in mean logMAR VA between groups at baseline or any study visit. VA was significantly reduced up to week 2 following surgery in both the groups. However, by month 1, VA in the Ex-PRESS group was no longer significantly different from baseline (P=0.23) and remained nonsignificant at subsequent visits up to 6 months. In the trabeculectomy group, VA remained significantly lower than baseline at each study visit. At 6 months, 47% of the trabeculectomy eyes compared with 16% of the Ex-PRESS eyes had lost ≥2 Snellen lines (P=0.01). Reasons for VA loss included cataract, central retinal vein occlusion, and diabetic retinopathy, however, in a significant number of cases no cause could be determined. None of the risk factors evaluated were associated with vision loss. Conclusions:Although there was no difference in mean VA between the Ex-PRESS and trabeculectomy groups at any time point, trabeculectomy eyes were more likely to lose ≥2 Snellen lines. In addition, VA recovered faster in the Ex-PRESS group.

Prospective Randomized Study Comparing Ex-PRESS to Trabeculectomy: 1-Year Results.

Purpose:To compare the efficacy and safety of the Ex-PRESS glaucoma shunt with standard trabeculectomy. Patients and Methods:Consenting patients with medically uncontrolled open-angle glaucoma were prospectively randomized to trabeculectomy or Ex-PRESS shunt both with mitomycin-C. Exclusion criteria included previous ocular surgery with the exception of clear cornea phaco or 1 previous trabeculectomy, uveitis, and vitreous in the anterior chamber. Standardized data collection sheets were completed at baseline and postoperative day 1, weeks 1 and 2, and months 1, 2, 3, 6, and 12. Primary outcome was intraocular pressure (IOP). Complete success was defined as an IOP between 5 and 18 mm Hg and a 20% reduction from baseline without medication. A sample size calculation determined that 52 eyes were required to detect a 2.0 mm Hg IOP difference with a power of 80%. Results:Sixty-four subjects were enrolled, 33 in the Ex-PRESS and 31 in the trabeculectomy group. IOP was not statistically significantly different between groups. Baseline and 1-year mean IOP was 22.0±6.8 versus 22.7±10.3 mm Hg (P=0.76) and 11.6±4.5 versus 11.3±4.5 mm Hg (P=0.81) in the trabeculectomy versus Ex-PRESS groups, respectively. Complete success was 57% versus 70% (P=0.28) in the trabeculectomy versus Ex-PRESS groups, respectively. There were no statistically significant differences in surgical time, number of glaucoma medications, visual acuity, central corneal thickness, endothelial cell counts, complications, interventions, or bleb morphology between the trabeculectomy and the Ex-PRESS groups. Conclusions:There was no statistically significant difference between the trabeculectomy and Ex-PRESS groups regarding IOP, success rates, complications, additional interventions, and bleb morphology.

Anti-inflammatory therapy after selective laser trabeculoplasty: a randomized, double-masked, placebo-controlled clinical trial.

PURPOSE To investigate the effect of anti-inflammatory therapy on selective laser trabeculoplasty (SLT) outcomes. DESIGN Randomized, double-masked, placebo-controlled trial. PARTICIPANTS Patients with primary open-angle or pseudo-exfoliation glaucoma. METHODS Patients undergoing SLT were randomized to receive placebo (artificial tears), prednisolone acetate 1%, or ketorolac tromethamine 0.5% eye drops 4 times per day for 5 days commencing immediately after SLT. MAIN OUTCOME MEASURES Change in intraocular pressure (IOP) from baseline to the 1-month post-SLT visit. RESULTS Mean change in IOP at the 1-month primary outcome time point, as well as all other time points, was not significantly different among groups (P = 0.99). Likewise, a repeated-measures, mixed-effects model did not find significant differences in IOP outcome at the 1-month time point (P = 0.95). The IOP was reduced in all groups at the 1-month post-SLT time point and all other time points, and no significant differences were found between groups using separate unadjusted cross-sectional analyses of variance (P > 0.15 for analyses at all time points). Treatment failure rates were not different among groups (P = 0.75), and at 1 year after SLT, the percentage of patients maintaining a 20% IOP reduction ranged from 18% to 22% in the 3 study groups. CONCLUSIONS Anti-inflammatory therapy after SLT does not seem to substantially influence the IOP-lowering effect of SLT. In this study of patients with low baseline IOP, SLT showed limited efficacy in achieving a sustained reduction in IOP.

Comparison of trabeculectomy versus Ex-PRESS: 3-year follow-up

Aims To compare the outcomes of Ex-PRESS versus trabeculectomy at 3 years. Methods Consenting patients aged 18–85 years with medically uncontrolled open-angle glaucoma scheduled for trabeculectomy were included in this study. 63 subjects were randomised to undergo Ex-PRESS (32) or trabeculectomy (31). Follow-up data included intraocular pressure (IOP), glaucoma medications, visual acuity (VA), complications and additional interventions. Complete success was defined as IOP between 5 and 18 mm Hg and 20% reduction from baseline without glaucoma medications, while qualified success was with or without glaucoma medications. Results Complete success at 2 and 3 years was 43% vs 42% (p=0.78) and 35% vs 38% (p=0.92) in Ex-PRESS versus trabeculectomy, respectively. Qualified success at 2 and 3 years was 59% vs 76% (p=0.20) and 52% vs 61% (p=0.43) in Ex-PRESS versus trabeculectomy, respectively. Mean IOP at 2 and 3 years was 12.5±5.1 mm Hg vs 10.3±3.7 mm Hg (p=0.07) and 13.3±4.5 mm Hg vs 11.1±4.4 mm Hg (p=0.10) for Ex-PRESS versus trabeculectomy, respectively. At 3 years, 47.6% of Ex-PRESS and 50% of trabeculectomy patients were on glaucoma medications (p=1.00). No difference in VA was found after 3 years (logarithm of minimum angle of resolution 0.43±0.4 vs 0.72±0.8 for Ex-PRESS vs trabeculectomy, p=0.11). When excluding patients who underwent reoperation VA was better in the Ex-PRESS group at 1, 2 and 3 years. There were no complications after the first year in either group. Conclusions We found no difference in success rates, mean IOP or other secondary outcomes between Ex-PRESS and trabeculectomy after 3 years of follow-up. Trial registration number NCT01263561; post results.

Anaesthetic plus dilating gel improves pupil dilation for cataract surgery

OBJECTIVE To evaluate the efficacy of a combination anaesthetic plus dilating gel (ADG) on pupil dilation (PD) and corneal anaesthesia (KA) compared to traditional preoperative pharmacotherapy for cataract surgery. DESIGN Prospective, noninferiority study. METHODS We studied 20 consenting adults who experienced unilateral cataracts and underwent routine cataract surgery, receiving the traditional preoperative pharmacologic regimen in the operated eye (control eye): diclofenac 0.1%, gentamicin 0.3%, cyclopentolate 1%, phenylephrine 2.5%, and tropicamide 1% 60 and 20 minutes prior to surgery. They then received tetracaine 0.5% and povidone-iodine 5% 10 minutes prior to surgery; and were given tetracaine 0.5%, povidone-iodine 5%, and lidocaine 2% gel 1 minute prior to surgery. Epinephrine 0.1%, 1 cc per 500 mL bag of balanced saline salt solution was administered during surgery. The nonoperated eye (study eye) received tetracaine 0.5%, povidone-iodine 5%, and 0.35 cc ADG gel (phenylephrine 10%, tropicamide 1%, diclofenac 0.1%, and lidocaine 2%) 60 and 10 minutes prior to surgery. PD and KA were measured at baseline, at 30 minutes, and at 5 minutes prior to surgery, and at 5 minutes after surgery. RESULTS There was no difference in PD (p = 0.2634) or KA (p = 0.6058) between the study eyes and the control eyes at baseline. Preoperatively, greater mydriasis was achieved in the study eye (7.95 ± 0.91 mm vs 7.17 ± 1.25 mm; p < 0.0001). There was no significant difference in preoperative KA between the study and control eyes (1.5 ± 2.2 mm vs 1.4 ± 2.1 mm; p = 0.77). CONCLUSIONS The combination ADG for preoperative preparation of cataract patients achieves at least equivalent dilation and corneal anaesthesia as the current preoperative pharmacologic regimen.

Evaluation of investigator bias in industry-funded clinical trials of latanoprost

OBJECTIVE To determine whether sponsorship of prostaglandin analogue (PGA) clinical trials results in investigator bias in outcomes when studying intraocular pressure (IOP). DESIGN Retrospective, observational cohort study. METHODS A PubMed search was performed for latanoprost or Xalatan, bimatoprost or Lumigan, and travoprost or Travatan, with limits to humans, clinical trials, and English language. Inclusion criteria included randomized controlled trials, open-angle glaucoma, monotherapy with a PGA, baseline IOP ≥ 21 mm Hg, washout period, and minimum 1-month follow-up. Each article was reviewed by 2 independent reviewers. The results of IOP for each PGA were categorized as being sponsored by the parent company (the company manufacturing the PGA); by the competing company (the company manufacturing competing glaucoma therapy); or by a nonindustry source. The mean IOP and changes in IOP from baseline were compared among the 3 categories of sponsorship. RESULTS Only studies involving latanoprost were analyzed because of the low number of studies meeting the inclusion criteria for bimatoprost and travoprost. We found 29 and 13 studies that provided 1- and 3-month data, respectively, for analysis. The mean baseline IOPs in the 3 groups (parent company, competing company, nonindustry) were not significantly different (p = 0.47). The mean IOP at 1 (p = 0.72) and 3 months (p = 0.59) and the change in IOP from baseline (p = 0.83 and 0.90, respectively) were not significantly different in the 3 groups. A random-effects metaregression controlling for the covariates of blinding, naïveté to PGAs, and baseline IOP < 24 mm Hg or ≥ 24 mm Hg did not change the findings. CONCLUSION There was no evidence of investigator bias in determining outcomes for IOP in these clinical trials of latanoprost.

Use of Machine Learning on Contact Lens Sensor–Derived Parameters for the Diagnosis of Primary Open-angle Glaucoma

PURPOSE To test the hypothesis that contact lens sensor (CLS)-based 24-hour profiles of ocular volume changes contain information complementary to intraocular pressure (IOP) to discriminate between primary open-angle glaucoma (POAG) and healthy (H) eyes. DESIGN Development and evaluation of a diagnostic test with machine learning. METHODS Subjects: From 435 subjects (193 healthy and 242 POAG), 136 POAG and 136 age-matched healthy subjects were selected. Subjects with contraindications for CLS wear were excluded. PROCEDURE This is a pooled analysis of data from 24 prospective clinical studies and a registry. All subjects underwent 24-hour CLS recording on 1 eye. Statistical and physiological CLS parameters were derived from the signal recorded. CLS parameters frequently associated with the presence of POAG were identified using a random forest modeling approach. MAIN OUTCOME MEASURES Area under the receiver operating characteristic curve (ROC AUC) for feature sets including CLS parameters and Start IOP, as well as a feature set with CLS parameters and Start IOP combined. RESULTS The CLS parameters feature set discriminated POAG from H eyes with mean ROC AUCs of 0.611, confidence interval (CI) 0.493-0.722. Larger values of a given CLS parameter were in general associated with a diagnosis of POAG. The Start IOP feature set discriminated between POAG and H eyes with a mean ROC AUC of 0.681, CI 0.603-0.765. The combined feature set was the best indicator of POAG with an ROC AUC of 0.759, CI 0.654-0.855. This ROC AUC was statistically higher than for CLS parameters or Start IOP feature sets alone (both P < .0001). CONCLUSIONS CLS recordings contain information complementary to IOP that enable discrimination between H and POAG. The feature set combining CLS parameters and Start IOP provide a better indication of the presence of POAG than each of the feature sets separately. As such, the CLS may be a new biomarker for POAG.

Diagnosis of Primary Open-Angle Glaucoma—Reply

Diagnosis of Primary Open-Angle Glaucoma To the Editor The Rational Clinical Examination article by Dr Hollands and colleagues1 reviewed the risk factors associated with primary open-angle glaucoma (POAG). Accurate measurement of intraocular pressure is one of the most important parameters in the diagnosis and management of POAG and may be performed by generalist physicians under certain conditions. Goldmann applanation tonometry (GAT) is the method most commonly used by ophthalmologists to measure intraocular pressure. However, GAT has some limitations. For example, it involves the use of a topical anesthetic and a fluorescein dye, which causes patient discomfort and has a small risk of corneal infection and allergic reactions. Measuring intraocular pressure with GAT requires training and may not be considered convenient by generalist physicians, who might prefer easy-to-use noncontact devices. It is important to emphasize that in clinical practice, intraocular pressure measurements obtained using GAT are not the same as those obtained using noncontact tonometers. Tonnu et al2 reported that the mean differences between GAT and a handheld tonometer (TonoPen, Reichert Technologies) and between GAT and a noncontact tonometer were 0.6 mm Hg and 0.7 mm Hg, respectively. The noncontact tonometer significantly overestimated GAT measurements at higher intraocular pressure and underestimated them at lower intraocular pressure. By using Bland-Altman analysis, Carrim and Lavy3 have shown that the upper and lower agreement limits between the handheld tonometer and GAT were 10.6 mm Hg and −9.6 mm Hg, respectively. These studies suggest that handheld and noncontact tonometers cannot be used as substitutes for GAT in the management of glaucoma. Therefore, generalist physicians should be cautious when using the commonly accepted threshold intraocular pressure of 22 mm Hg if measurements were not performed by GAT. Furthermore, the authors neglected to evaluate central corneal thickness, which is an important component of the common ocular examination. A number of devices that provide rapid, convenient, noncontact, and objective central corneal thickness measurements are available. The change in the intraocular pressure reading could range from 0.1 mm Hg to 0.7 mm Hg per 10 μm of change in central corneal thickness.4 Accurate assessment of intraocular pressure requires knowledge of central corneal thickness.4 The Ocular Hypertension Treatment Study and Early Manifest Glaucoma Trial showed that central corneal thickness is an important and predictive risk factor for change from ocular hypertension to POAG and for progression of POAG in patients with higher baseline intraocular pressure.4,5 Therefore, it would be of interest to assess the diagnostic accuracy after considering central corneal thickness.

Career satisfaction and surgical practice patterns among female ophthalmologists

PURPOSE To identify gender differences in career satisfaction and practice patterns among Ontario ophthalmologists. METHODS Survey mailed to all Ontario female ophthalmologists (n = 65) and a random sample of male ophthalmologists (n = 72). RESULTS Men reported performing more operations per month (p = 0.039) and more operations in the last typical year (p = 0.003). More men than women were doing laser refractive surgery (p = 0.004). There were no gender differences in the proportion performing eye surgery or in the hours worked per week or weeks worked per year. Women reported being primarily responsible for their children for significantly more hours per week than men (p = 0.0003). There were no gender differences in any of the parameters of career satisfaction evaluated: number of hours worked, number of hours in the operating room (OR), balance with personal life, flexibility of work schedules, ability to structure work, relationship with colleagues and relationship with OR staff. INTERPRETATION Despite spending significantly more hours as the primary supervisor of their children, female ophthalmologists were maintaining the same work week as their male colleagues and reported equal career satisfaction. Further investigation is needed to explore the differences between male and female ophthalmologists in the reported number of operations performed.