Florent Aptel

Le glaucome est une pathologie fréquente principalement due à une élévation de la pression intraoculaire. La pression intraoculaire est le fruit d’un équilibre entre la production du liquide qui remplit la portion antérieure de l’œil - l’humeur aqueuse - et son élimination. Les traitements du glaucome peuvent donc agir selon deux mécanismes : la réduction de la production d’humeur aqueuse par la destruction partielle ou l’inhibition pharmacologique du corps ciliaire, structure responsable de la production de l’humeur aqueuse, ou la facilitation de l’évacuation de l’humeur aqueuse en dehors de l’oeil. De nombreuses méthodes physiques peuvent être utilisées pour détruire le corps ciliaire : lasers, cryothérapie, micro-ondes, etc. Néanmoins, toutes ces méthodes ont deux inconvénients majeurs qui limitent leur utilisation : elles sont peu sélectives de l’organe à traiter, entraînant souvent des dommages des structures adjacentes, et elles présentent une relation effet-dose très inconstante, empêchant de prévoir avec précision l’effet du traitement. L’objectif de ce travail de thèse est le développement d’un dispositif ultrasonore de coagulation du corps ciliaire circulaire, comprenant 6 transducteurs piézoélectriques en forme de segments de cylindre, et générant 6 lésions segmentaires s’inscrivant dans un anneau de diamètre similaire à celui formé par le corps ciliaire. Les expérimentations animales ont montré une nécrose de coagulation sélective des zones du corps ciliaire traitées par le dispositif. Le premier essai clinique a montré que cette méthode était bien tolérée et permettait une réduction importante, prédictible et maintenue dans le temps de la pression intraoculaire

Purpose. To investigate the cost utility of STN1013001, a latanoprost cationic emulsion, versus Latanoprost in patients with open-angle glaucoma or ocular hypertension (OAG/OHT) and concomitant ocular surface disease (OSD) in France. Methods. An early Markov model, including 7 health states and a 1-year cycle length, was developed to estimate the cost utility of STN1013001 versus Latanoprost from the French health system perspective over a 5-year time horizon. The model was populated with pooled data (treatment adherence, quality of life, disease progression, and resource utilization) collected, via a questionnaire, from a convenience sample of 5 French glaucoma specialists. Remaining data were retrieved from published sources. Half-cycle correction and 2.5 real social discount rate were applied to costs (in 2020), life years saved (LYS), and quality-adjusted life years (QALYs). The incremental cost-utility ratio (ICUR) was contrasted against the informal willingness-to-pay (WTP) range for incremental LYS or QALY gained (30,00050,000) suggested for France. One-way and probabilistic sensitivity analyses tested the robustness of the baseline ICUR. Results. Over a 5-year time horizon, STN1013001 resulted in an incremental 0.35 QALYs gained at an incremental cost of 7.39 compared to Latanoprost, resulting in an ICUR of 21.26. This is well below the lower limit of the unofficial WTP range proposed for France. Sensitivity analyses confirmed the robustness of the baseline results. Conclusion. Once on the market, STN1013001 will provide the French health system with a cost-effective treatment versus Latanoprost for OAG/OHT+OSD patients. These results should be confirmed by future economic evaluations carried out alongside empirical trials.

Purpose: To describe the glaucoma surgery offer in France in 2016.Methods: We used the French National Health Care System database to identify all medical procedures carried out in 2016. The study investigated the entire population aged 30 years and older that had undergone glaucoma surgery, alone or combined with another surgery. We calculated the incidence of surgeries per 100 000 inhabitants 30 years of age and older performed by ophthalmologists carrying out at least 50 procedures annually, the number of surgeons doing these surgeries, the mean age of these practitioners, and the number of surgeons older than 55 years.Results: In 2016, 16 854 glaucoma surgeries were performed in patients aged 30 years and older, for an incidence of 40.8 per 100 000 inhabitants aged 30 years and older. The most frequent procedure performed was trabeculectomy followed by non‐penetrating deep sclerectomy (16.7 and 11.7, respectively, per 100 000 inhabitants 30 years of age and older). Private practice glaucoma surgery accounted for 47% of the activity of surgeons performing at least 50 surgeries per year and 60% of the total surgical activity. Of the private practice ophthalmologists performing at least 50 glaucoma surgery procedures per year, 58.5% were over 55 years of age, and 23.5% of public hospital ophthalmologists were over 55 years of age.Conclusions: This study demonstrates that surgeons performing glaucoma surgeries are often older. It is necessary to take note of the country’s educational capacity to ensure that the number of ophthalmological surgeons remains adapted to demand.

Precis: We compared the quality of instillation of topical treatments from single-dose (SGD) or multidose (MTD) containers in glaucoma patients and showed neither a significant difference between the type of container nor a significant relationship to upper limb mobility. Purpose: To describe and compare the quality of instillation of topical treatments with SGD or MTD containers in glaucoma patients. To assess factors likely to influence instillation, particularly the upper limb mobility. Materials and Methods: This multicenter, cross-sectional study included open-angle glaucoma patients with the same self-instilled treatment over at least 3 months. Patients were asked to successively self-administer a drop of artificial tears from SGD and MTD containers in front of an observer. The order of instillation (eye and container) was randomized. Correct instillation was defined as the administration of 1 drop in the lower fornix, without any contact between the tip of the device and the ocular surface. The Quick Disabilities of the Arm, Shoulder, and Hand self-questionnaire assessed upper limb mobility. Results: A total of 239 eyes from 173 patients were included. For the worst eye group 33% of patients performed correct instillation with MTD versus 32% using SGD (P=1). In the best eye group, 31.7% patients performed a correct instillation with MTD administration versus 27.5% with SGD (P=0.327). Multivariate analysis showed a significant association between an inadequate SGD instillation, old age (P=0.021), the severity of the visual field deficits (P=0.035), and a low quality of life score (P=0.028). No association existed between the Quick Disabilities of the Arm, Shoulder, and Hand score and the quality of instillation. Conclusions: These results suggest that the handling of single-use containers should be practiced by patients and evaluated by physicians, especially for the elderly population and those with advanced glaucoma. No difference in instillation quality was found between SGD and MTD.

Precis: Ultrasound cycloplasty (UCP) treatment using high-intensity focused ultrasound is an effective and safe therapy to reduce intraocular pressure (IOP) in patients with refractory glaucoma over a 3-year period. Purpose: The purpose of this study was to evaluate the 3-year efficacy and safety of UCP in patients with refractory glaucoma. Patients and Methods: In all, 104 patients with refractory glaucoma recruited from 2 university hospitals underwent UCP. Examinations were performed 7 days, 1 week, 1, 3, 6, 12, 24, and 36 months after the UCP procedure. Primary outcomes were therapeutic success at 3 years (IOP reduction from baseline ≥20% and IOP >5 mm Hg without other surgical procedures) and vision-threatening complications. Secondary outcomes included mean IOP change from baseline at each follow-up visit, medication use, complications, and subsequent UCP and/or other postsurgical interventions. Results: At 3 years post-UCP, the therapeutic success rate was 55%. For 75% of the patients, results were obtained with only one procedure. For the overall study population, IOP was reduced significantly (P<0.005) from 27.6±8.9 mm Hg (n=3.0 topical hypotensive medication) to 17.0±6.8 mm Hg at 36 months (n=2.8 topical hypotensive medication) (33% reduction). For the success patients, the IOP was initially 29.3±8.8 mm Hg (n=3.0 topical hypotensive medication) and 15.6±4.3 mm Hg at 36 months (n=2.8 topical hypotensive medication) (43% reduction). The rate of complications was low and there were no cases of phthisis. Conclusion: The UCP procedure was efficacious with few complications and should be considered as an alternative to other IOP-lowering therapies including laser cyclocoagulation in patients with refractory glaucoma.

Purpose: To assess the status of the cone photoreceptors using adaptive optics flood illumination ophthalmoscopy in patients with birdshot chorioretinopathy and to study their relationship with optical coherence tomography (OCT) angiography. Methods: Seventeen patients with birdshot chorioretinopathy were studied using standard automated perimetry, color vision testing, fluorescein angiography, indocyanine green angiography, spectral domain OCT, enhanced depth imaging OCT, and adaptive optics flood illumination ophthalmoscopy (rtx1, Imagine Eyes, Orsay, France) in a 90 × 90-μm area at 1.5° temporal of the fovea and OCT angiography (Spectralis OCT2, Heidelberg Engineering, Heidelberg, Germany). For adaptive optics flood illumination ophthalmoscopy, spectral domain OCT, and OCT angiography, a control group of 12 healthy patients (12 eyes) matched for age, sex, and refractive error was included. Results: After excluding low-quality adaptive optics flood illumination ophthalmoscopy images, 12 eyes (12 patients, 7 women, mean age 53.5 ± 10.8 years) were analyzed. Best-corrected visual acuity was 0.01 ± 0.03 LogMAR (20/25 Snellen equivalent), and foveal threshold at standard automated perimetry was 35.2 ± 3.0. Cone density at 1.5° of the fovea in the birdshot chorioretinopathy group (11,435.25 ± 4,342.9 cells/mm²) was significantly smaller than in the control group (24,594.04 ± 4,764.3 cells/mm², P < 0.001). In the same area, birdshot chorioretinopathy eyes showed disruption of the ellipsoid/interdigitation zone and vascular abnormalities, such as capillary loops (58.3%), increased superficial intercapillary spaces (75%), increased deep intercapillary spaces (58.3%), capillary dilations (58.3%), telangiectatic vessels (66.6%), and absence of choriocapillary flow (58%). Cone density at 1.5° was associated with duration of the disease (Spearman's rho −0.8, P = 0.01), although it was not associated with OCT angiography abnormalities in the same area. Conclusion: Birdshot chorioretinopathy can result in a reduction in cone density and development of macular vascular abnormalities even in the presence of preserved visual function.

Purpose: The aim of this study was to evaluate the efficacy and safety of ultrasonic cyclocoagulation in severe or refractory glaucoma, and to analyze the procedure-related inflammation. Patients and Methods: In this retrospective study, 15 eyes of 13 patients suffering from severe or refractory glaucoma with uncontrolled intraocular pressure of ⩾21 mmHg underwent 8-s ultrasonic cyclocoagulation. A complete ophthalmic evaluation, quality of life assessment using Glau-Qol-17, endothelial cell count, and flare measurement were performed. Primary outcome was qualified surgical success (defined as intraocular pressure reduction from baseline ⩾20% and intraocular pressure >5 mmHg without hypotensive medication adjunction). Secondary outcomes were flare, endothelial cell loss, and quality of life. Results: Qualified success was achieved in 67% of eyes at 6 months (mean intraocular pressure reduction = 42% in these eyes). During the first month after the procedure, the mean flare reached its maximum value when the intraocular pressure was minimal; the flare slowly decreased until normalization at month 3 when the maximal intraocular pressure was noted. At month 3, there was moderate but significant endothelial cell loss (11%), and no significant alteration in quality of life was demonstrated. Conclusion: The efficacy of ultrasonic cyclocoagulation in the present study is comparable to that reported in the literature. The kinetics of intraocular pressure and flare suggest that postoperative inflammation could be partly responsible for the early intraocular pressure decrease. The moderate endothelial cell loss, which could be caused by localized heating, and the preservation of quality of life confirm the safety of ultrasonic cyclocoagulation.