Florent Aptel

Optical coherence tomography quantitative analysis of iris volume changes after pharmacologic mydriasis.

PURPOSEnTo describe a method using anterior segment optical coherence tomography (AS OCT) for estimating iris volume. To quantify changes in iris volume induced by pharmacologic mydriasis in narrow-angle eyes predisposed to angle-closure compared with normal open-angle eyes.nnnDESIGNnCross-sectional study.nnnPARTICIPANTSnThirty fellow eyes of 30 patients who had an episode of primary acute angle-closure and 30 eyes of 30 normal age- and gender-matched subjects with open angles. All fellow eyes had a patent laser peripheral iridotomy.nnnMETHODSnIris volume and all biometric measurements were performed before and after instillation of 1% tropicamide and at least 1 week later 10% phenylephrine. Iris volume was estimated using AS OCT radial sections of the iris and a customized image-processing software.nnnMAIN OUTCOME MEASURESnIris volume, pupil diameter, angle configuration including angle opening distance at 500 mum (AOD 500) and trabecular-iris space at 500 mum (TISA 500), AS OCT anterior chamber depth, and A-scan ultrasonography axial length before and after pupil dilation.nnnRESULTSnIris volumes measured before dilation of the pupil were 44.94+/-2.1 mm(3) and 44.29+/-3.9 mm(3) in the fellow eyes and open-angle eyes, respectively, which was not significantly different (P>0.1). Thirty minutes after instillation of 1% tropicamide, mean iris volume increased significantly in the fellow eyes (from 44.94+/-2.1 mm(3) to 49.92+/-2.9 mm(3); P<0.01), whereas it decreased significantly in the open-angle eyes (from 44.29+/-3.9 mm(3) to 37.88+/-2.2 mm(3); P<0.01). Similar changes were observed after instillation of 10% phenylephrine. Based on multivariate analysis, significant predictors of increase in iris volume after pupil dilation were eyes predisposed to angle-closure compared with open-angle eyes (P = 0.008), larger pupil diameter (P = 0.02), and brown eyes (P = 0.01). Relative iris volume increase was correlated significantly with AOD 500 and TISA 500 relative decrease in the narrow-angle group (P<0.05).nnnCONCLUSIONSnThe iris volume may be estimated with AS OCT. The iris volume increases after pupil dilation in narrow-angle eyes predisposed to acute angle closure. In those patients, this biometric change is associated with a narrowing of the angle despite a patent laser peripheral iridotomy.nnnFINANCIAL DISCLOSURE(S)nThe author(s) have no proprietary or commercial interest in any materials discussed in this article.

Efficacy and tolerability of prostaglandin analogs: a meta-analysis of randomized controlled clinical trials.

AimThis systematic meta-analysis was performed to evaluate the intraocular pressure (IOP) lowering effects and tolerability of latanoprost, bimatoprost, and travoprost. MethodsClinical trials published up to July 2006 were thoroughly searched using all available databases and resources. The inclusion criteria were prospective randomized controlled clinical trials; patients with primary open-angle glaucoma or ocular hypertension; and prostaglandin monotherapy, without systemic/ocular medications or laser/surgery that could affect IOP within the past 3 months. Study quality was assessed with the Jadad scoring system, and potential bias was eliminated by robust statistical and independent reviews of publications. The main outcome measures were efficacy assessed by IOP (taken at 8 AM, noon, 4 PM, and 8 PM) change at 3 months from baseline and tolerability assessed by the incidence of conjunctival hyperemia. ResultsEight trials were identified (n=1610 patients). IOP change from baseline was statistically significantly greatest with bimatoprost, compared with latanoprost at all time points [weighted mean (WM) 8 AM: WM=0.50u2009mm Hg; P=0.05; 95% confidence intervals (CIs) 0.01-0.99; noon: WM=1.17u2009mm Hg; P<0.001; 95% CI 0.68-1.66; 4 PM: WM=0.78u2009mm Hg; P=0.003; 95% CI 0.26-1.29; 8 PM: WM=0.67u2009mm Hg; P=0.04; 95% CI 0.02-1.32], and with travoprost during the daytime (8 AM: WM=1.02u2009mm Hg; P=0.004; 95% CI 0.32-1.72; noon: WM=0.86u2009mm Hg; P=0.02; 95% CI 0.12-1.59). Latanoprost and travoprost were comparable in their ability to reduce IOP at all time points (P≤0.82). The incidence of hyperemia was less with latanoprost and travoprost [latanoprost vs. bimatoprost: relative risk=0.59; P<0.001; 95% CI 0.50-0.69; travoprost vs. bimatoprost: relative risk=0.84; P=0.05; 95% CI 0.70-1.00]. ConclusionsThe findings suggest a greater efficacy of bimatoprost compared with latanoprost and travoprost, although the incidence of hyperemia was lower with the latter 2 agents.

Miniaturized high-intensity focused ultrasound device in patients with glaucoma: a clinical pilot study.

PURPOSEnTo evaluate the relative safety and potential efficacy of high-intensity focused ultrasound cyclocoagulation by a miniaturized annular device containing six piezoceramic transducers in patients with refractory glaucoma.nnnMETHODSnThis was a three-center prospective interventional pilot study. Twelve eyes of 12 patients with refractory glaucoma were insonified using a ring-shaped probe containing six miniaturized high-frequency transducers operating at 21 MHz. Ultrasound biomicroscopy (UBM) and a complete ophthalmic examination were performed before the procedure and at 1 day, 1 week, 1 month, and 3 months after the procedure. Additional visits were performed 6 and 12 months after the procedure.nnnRESULTSnIntraocular pressure was significantly reduced (P < 0.01) from a mean preoperative value of 37.9 ± 10.7 mm Hg to a mean postoperative value of 27.3 ± 12.4, 25.2 ± 11.3, 25.2 ± 7.7, 24.8 ± 9.8, and 26.3 ± 5.1 mm Hg at 1 day, 1 week, 1 month, 3 months, and 6 months, respectively, and to a mean value of 24.7 ± 8.5 at the last follow-up visit. No major intraoperative or postoperative complications occurred. Minor postoperative corneal complications developed in four patients with previous corneal abnormalities: superficial punctate keratitis (n = 3) and central superficial corneal ulceration (n = 1). UBM showed cystic involution of the ciliary body in 9 of the 12 eyes and a suprachoroidal fluid space in 8 of the 12 eyes.nnnCONCLUSIONSnUltrasonic circular cyclocoagulation using high-intensity focused ultrasound delivered by a circular miniaturized device containing six piezoceramic transducers seems to be an effective and well-tolerated method to reduce intraocular pressure in patients with refractory glaucoma.

Ultrasound biomicroscopy and optical coherence tomography imaging of filtering blebs after deep sclerectomy with new collagen implant

Purpose To identify the clinical and anatomic characteristics of filtering blebs after glaucoma surgery with a new biodegradable collagen implant, Ologen, using ultrasound biomicroscopy (UBM) and Visante anterior segment optical coherence tomography (OCT). Methods The authors conducted a prospective interventional case series in 15 eyes with open-angle glaucoma. The authors performed limbal-based deep sclerectomy with Ologen implantation in the scleral bed. UBM, Visante anterior segment OCT, and a complete ophthalmic examination were performed at each follow-up visit, at 1 day, and 1, 4, and 12 weeks postoperatively. Results Intraocular pressure (IOP) was significantly reduced (p<0.001) from a mean preoperative value of 24.2±6.8 mmHg (n=2.82 glaucoma medications) to a mean postoperative value of 8.1±1.2 (n=0), 8.5±1.3 (n=0), 11.7±3.2 (n=0), and 14.2±3.9 mmHg (n=0.33) at 1 day, and 1, 4, and 12 weeks, respectively. Lower IOP correlated with bleb height and low trabeculocorneal membrane thickness (r=0.79, p<0.01, r=0.91, p<0.001) based on UBM examination. Lower IOP correlated with thin bleb wall, large subconjunctival fluid spaces, and low bleb tissue reflectivity (r=0.81, p<0.01, p<0.001, and p<0.001) based on OCT examination. No postoperative complications were reported. Conclusions UBM and OCT examinations are useful methods to evaluate outflow mechanisms after glaucoma surgery. Deep sclerectomy with Ologen implantation seems to be an effective and well-tolerated method to reduce IOP.

Development of a Miniaturized HIFU Device for Glaucoma Treatment With Conformal Coagulation of the Ciliary Bodies

This study examined the feasibility of high-intensity focused ultrasound (HIFU) for glaucoma treatment with conformal coagulation of the ciliary bodies (CB). A miniaturized high frequency (21 MHz) device was developed, based on the geometry of the eye and adapted to the anatomy of the rabbit eyeball. Six line-focus lesions were distributed along a circle and produced by six cylindrical transducers. To be conformal, the numerical model predicted an intensity of 6.9 W/cm(2), with exposure duration of 3 s ON (powered per sector). In vivo experiments were conducted on two rabbits. A significant intraocular pressure reduction was noted (-45% and -31%). Histology demonstrated conformal and homogeneous coagulation of the CB without side effects.

Structure–Function Relationships Using Spectral-Domain Optical Coherence Tomography: Comparison With Scanning Laser Polarimetry

PURPOSEnTo evaluate and compare the regional relationships between visual field sensitivity and retinal nerve fiber layer (RNFL) thickness as measured by spectral-domain optical coherence tomography (OCT) and scanning laser polarimetry.nnnDESIGNnProspective cross-sectional study.nnnMETHODSnOne hundred and twenty eyes of 120 patients (40 with healthy eyes, 40 with suspected glaucoma, and 40 with glaucoma) were tested on Cirrus-OCT, GDx VCC, and standard automated perimetry. Raw data on RNFL thickness were extracted for 256 peripapillary sectors of 1.40625 degrees each for the OCT measurement ellipse and 64 peripapillary sectors of 5.625 degrees each for the GDx VCC measurement ellipse. Correlations between peripapillary RNFL thickness in 6 sectors and visual field sensitivity in the 6 corresponding areas were evaluated using linear and logarithmic regression analysis. Receiver operating curve areas were calculated for each instrument.nnnRESULTSnWith spectral-domain OCT, the correlations (r(2)) between RNFL thickness and visual field sensitivity ranged from 0.082 (nasal RNFL and corresponding visual field area, linear regression) to 0.726 (supratemporal RNFL and corresponding visual field area, logarithmic regression). By comparison, with GDx-VCC, the correlations ranged from 0.062 (temporal RNFL and corresponding visual field area, linear regression) to 0.362 (supratemporal RNFL and corresponding visual field area, logarithmic regression). In pairwise comparisons, these structure-function correlations were generally stronger with spectral-domain OCT than with GDx VCC and with logarithmic regression than with linear regression. The largest areas under the receiver operating curve were seen for OCT superior thickness (0.963 ± 0.022; P < .001) in eyes with glaucoma and for OCT average thickness (0.888 ± 0.072; P < .001) in eyes with suspected glaucoma.nnnCONCLUSIONSnThe structure-function relationship was significantly stronger with spectral-domain OCT than with scanning laser polarimetry, and was better expressed logarithmically than linearly. Measurements with these 2 instruments should not be considered to be interchangeable.

Histologic effects of a new device for high-intensity focused ultrasound cyclocoagulation.

PURPOSEnTo evaluate the histologic effects and clinical outcomes of high-intensity focused ultrasound (HIFU) delivered by miniaturized annular transducers for ciliary body coagulation in an animal study.nnnMETHODSnEighteen eyes of 18 rabbits were insonified with a ring comprising a six-sector transducer, to produce a 12.8-mm-diameter circular lesion. Six sectors were activated in six rabbits (group 1), five sectors in six rabbits (group 2), and four sectors in six rabbits (group 3) at 2 W acoustic power. The rabbits were examined before treatment (day 0) and after treatment on days 1, 7, 15, 21, and 28. Detailed qualitative and semiquantitative histopathologic analyses of the enucleated eyes were performed.nnnRESULTSnIn the treated eyes, intraocular pressure changes ranged from -16.6 mm Hg (-55.3%) at day 28 to -8.9 mm Hg (-29.7%) at day 7 in group 1, from -4.7 mm Hg (-25.5%) at day 28 to -1.4 mm Hg (-7.6%) at day 21 in group 2 and from -7.9 mm Hg (-28.1%) at day 28 to +2.0 mm Hg (+7.1%) at day 7 in group 3. No macroscopic abnormalities were observed in the anterior segment or fundus. Histologic examination showed segmental-to-annular lesions in the ciliary processes, caused mainly by coagulation necrosis, whereas the sclera and lens appeared undamaged. Inflammation was very limited.nnnCONCLUSIONSnUltrasonic coagulation of the ciliary body with HIFU delivered via a circular miniaturized transducer seemed to be an effective and well-tolerated method of reducing intraocular pressure in an animal study.

Therapeutic applications of ultrasound in ophthalmology

Therapeutic ultrasound, although less well known than ultrasound for diagnostic imaging, has become a topic of growing interest in ophthalmology. High intensity focused ultrasound (HIFU) for the treatment of glaucoma and ultrasonic drug delivery are the two main areas of research and potential clinical applications. For the treatment of glaucoma, the specific advantage of HIFU, particularly when compared to the laser, is that the energy can be focused through optically opaque media, especially through the sclera which is a strongly light-scattering medium. HIFU is therefore a possible method for partial coagulation of the ciliary body (an anatomical structure responsible for the production of the liquid filling the eye) and, hence, reducing intraocular pressure and the risk of glaucoma. Ocular drug bioavailability also remains a challenge, being limited by multiple barriers to drug entry and lacrimal drainage, and making it difficult to achieve a sufficient drug concentration for numerous diseases of the front and back of the eye. As the front wall of the eye (cornea and anterior sclera) is a pathway for topically applied drugs, locally applied ultrasound has been proposed as a way of enhancing the delivery and activity of drugs and genes. Despite the fact that experimental studies seem to confirm the potential benefit of ultrasound ocular drug delivery, there is still a lack of clinical evidence. The aim of this contribution is to provide an update on recent advances in the field of therapeutic ultrasound in ophthalmology.

Biometric Analysis of Pigment Dispersion Syndrome Using Anterior Segment Optical Coherence Tomography

PURPOSEnTo compare anterior chamber volume (ACV), iris volume, and iridolenticular contact (ILC) area before and after laser peripheral iridotomy (LPI) in eyes with pigment dispersion syndrome (PDS) using anterior segment optical coherence tomography (AS OCT) and image processing software.nnnDESIGNnCross-sectional study.nnnPARTICIPANTSnEighteen eyes of 18 patients with PDS; 30 eyes of 30 controls matched for age, gender, and refraction.nnnMETHODSnAnterior segment OCT imaging was performed in all eyes before LPI and 1, 4, and 12 weeks after LPI. At each visit, 12 cross-sectional images of the AS were taken: 4 in bright conditions with accommodation (accommodation), 4 in bright conditions without accommodation (physiological miosis), and 4 under dark conditions (physiologic mydriasis). Biometric parameters were estimated using AS OCT radial sections and customized image-processing software.nnnMAIN OUTCOME MEASURESnAnterior chamber volume, iris volume-to-length ratio, ILC area, AS OCT anterior chamber depth, and A-scan ultrasonography axial length.nnnRESULTSnBefore LPI, PDS eyes had a significantly greater ACV and ILC area than control eyes (P<0.01) and a significantly smaller iris volume-to-length ratio than the controls (P<0.05). After LPI, ACV and ILC area decreased significantly in PDS eyes, but iris volume-to-length ratio increased significantly (P<0.02) and was not significantly different from that of controls. These biometric changes were stable over time. Iris volume-to-length ratio decreased significantly from accommodation to mydriasis and from miosis to mydriasis, both in PDS and control eyes (P<0.01). In PDS eyes, ILC area decreased significantly from accommodation to mydriasis, both before and after LPI (P<0.01). On multivariate analysis, greater anterior chamber (AC) volume (P<0.02) and larger AC depth (P<0.05) before LPI were significant predictors of a larger ILC area.nnnCONCLUSIONSnPigment dispersion syndrome eyes do not have an iris that is abnormally large, relative to the AS size, but have a weakly resistant iris that is stretched and pushed against the lens when there is a pressure difference across the iris.nnnFINANCIAL DISCLOSURE(S)nThe author(s) have no proprietary or commercial interest in any materials discussed in this article.

L’interprétation des essais cliniques

Clinical trials are playing an increasingly crucial role in modern evidence based medicine, allowing for rigorous scientific evaluation of treatment strategies and validation of patient care. The results of clinical trials often form the rational basis from which physicians draw information used to adapt their therapeutic practices. Critical reading and analysis of trials involves the assessment of whether the available data provide enough credible evidence that the treatment will result in a clinically significant and relevant improvement. Evaluating the quality of a clinical trial is a process that draws upon sometimes complex methodological and statistical concepts, with which the reader should nonetheless be familiar in order to come to impartial conclusions regarding the raw data presented in the clinical trials. The goal of the current article is to review the methodological and statistical concepts required for the design and interpretation of clinical trials, so as to allow for a critical analysis of publications or presentations of clinical trials. The first section describes the major methodological principles of clinical trial design required for a rigorous evaluation of the treatment benefit, as well as the various pitfalls or biases that could lead to erroneous conclusions. The second section briefly describes the main statistical tests used in clinical trials, as well as certain situations that may increase the risk of false positive findings (type 1 error), such as multiple, subgroup, intermediate and non-inferiority analysis.