Minimally Invasive Surgery, Implantable Sensors, and Personalized Therapies

Glaucoma management has changed dramatically over the last decades, through clinical advances and technological revolutions. This review discusses the latest innovations and challenges faced in the field around three major axes: minimally-invasive glaucoma surgery (MIGS), implantable sensors and injectable therapeutics. Indeed, the vast number of recently developed MIGS techniques has not only provided clinicians with a wide range of therapeutic options, but they have also enabled them to adjust their therapies more finely which may have contributed a more patient-centric decision-making process. Yet, despite considerable advances in the field, the wide heterogeneity in clinical trial designs blurs the surgical outcomes, specificities and indications. Thus, more high-quality data are required to make the choice of a specific MIGS procedure more than an educated guess. Beyond the scope of MIGS, the potential of IOP telemetry for self-assessment of IOP-control through implantable sensors is developing into a real option for clinicians and an empowering opportunity for patients. Indeed, providing patients with direct feedback enables them to take control and have a clearer representation of their care, in turn leading to a better control of the disease. However, there are potential issues with self-monitoring of IOP, such as increased anxiety levels induced by measured IOP fluctuations and peaks, leading to patients self-treating during IOP spikes and additional office visits. Furthermore, the advent of implantable therapeutics may soon provide yet another step towards personalized glaucoma treatment, by offering not only an efficient alternative to current treatments, but also a therapeutic option that may better adapt to patients’ lifestyle. After several decades of relative stagnation through the last century, glaucoma has now entered what many view as a golden age for the specialty. Like every revolution, this one brings its fair share of uncertainty, clinical questioning and uneasy periods of adaptation to ever-changing expectations. Yet, while it is impossible to guess what the landscape of glaucoma surgery will be like in ten or fifteen years, data suggest a bright outlook both for patients and clinicians. Keywords: Glaucoma; MIGS; Quality of Life; Telemetry; Eyemate; Bimatoprost S

A Prospective Analysis of iStent inject® Microstent Implantation: Surgical Outcomes, Endothelial Cell Density and Device Position at 12-month

Contexte : Le dispositif ophtalmologique iStent inject® (Glaukos Corporation, CA, USA) est un micro-bypass conçu pour être implanté à travers le trabéculum, afin d’améliorer le flux de l’humeur aqueuse de la chambre antérieure vers le canal de Schlemm. Bien que plusieurs études préliminaires aient démontré un potentiel d'abaissement de la tension intraoculaire suite à son implantation, l’impact sur les structures oculaires et les mécanismes exacts par lesquels cet effet est produit restent spéculatifs. La présente étude utilise l'imagerie par tomographie en cohérence optique du segment antérieur (OCT-SA) in-vivo pour analyser les résultats cliniques, le positionnement des dispositifs et leur effet sur les structures ophtalmiques, ainsi que d’hypothétiques associations entre ces facteurs. Méthode : Dans cette étude comparative prospective, 54 yeux de 42 sujets atteints à la fois de cataracte et d’un glaucome à angle ouvert débutant à modéré ont été inclus dans le groupe traitement. Tous ces yeux ont reçu 2 dispositifs iStent inject® combinés à une phacoémulsification. Les patients ont été suivis sur une période post-opératoire de 12 mois. Un protocole d’imagerie OCT-SA a été réalisé après 3 et 12 mois. Deux groupes témoins ont été constitués : les 30 yeux non-opérés des patients inclus pour le groupe de comparaison des structures oculaires vierges, et 25 yeux préalablement opérés de la cataracte pour le groupe de comparaison des complications post-opératoires. Les comparaisons inter-groupe ont été réalisées à l’aide du test de Student, et l’analyse d’associations pronostiques s’appuie sur des régressions linéaires multiples et coefficients de corrélation. Résultats : La tension intraoculaire moyenne du groupe traitement à diminué de 16,5 ± 4,2 mmHg en préopératoire à 15,1 ± 3,7 mmHg à 12 mois (-8,7 % ; p = 0,004). Dans le même temps, le nombre de médicaments anti-hypertenseurs a diminué de 1,8 ± 1,0 à 0,5 ± 0,9 (-72,2 % ; p < 0,001). Une tension intraoculaire ≤ 18 mmHg a été obtenue sans traitement dans 58,8% des yeux opérés. Aucune complication sérieuse n'a été observée durant le suivi. À l'OCT-SA, 44,9% des stents étaient enfuis dans le trabéculum, sans communication avec la chambre antérieure. La position des dispositifs est demeurée inchangée entre les deux analyses. L'analyse par régression a relevé plusieurs facteurs de risque significatifs : la dilatation du canal de Schlemm (RR = 0,230; p = 0,003), l’extrusion des dispositifs en chambre antérieure (RR = 0,993; p = 0,012), le nombre de dispositifs visibles par gonioscopie (RR = 0,406; p = 0,040), le nombre de traitements préopératoires (RR = 2,214; p = 0,001), la tension intraoculaire préopératoire (RR = 0,184; p = 0,006). La densité des cellules endothéliales des yeux traités a diminué de 14,6% suite à l’opération combinée (p < 0,001), comparé à 14.4% dans le groupe contrôle (p = 0.025). Conclusion : Cette étude souligne le potentiel thérapeutique de la chirurgie par iStent inject® dans le glaucome primaire à angle ouvert et pseudoexfoliatif. Elle révèle qu’une large proportion des dispositifs sont implantés en profondeur dans les structures oculaire. Elle confirme également que les résultats chirurgicaux sont directement associés à l’extrusion du stent en chambre antérieure et suggère l’amplitude de dilatation du canal de Schlemm comme indicateur pronostique. Enfin, elle montre la stabilité des dispositifs lors du suivi post-opératoire, soulignant l'importance du positionnement initial de l’implant

Intraocular pressure variations after intravitreal injections measured with an implanted suprachoroidal telemetry sensor

Purpose: Intravitreal injections (IVIs) may create transient intraocular pressure (IOP) elevation. This report describes continuous IOP fluctuations following multiple IVI measured with a permanent implantable sensor. Patients and Methods: We report the case of a 49-year-old white glaucomatous male with refractory macular edema secondary to central retinal vein occlusion in his left eye who underwent deep sclerectomy combined with the implantation of a suprachoroidal tonometry sensor. Serial IOP measurements were performed immediately before and after each IVI over a 1-year period. Results: During the first 7 months following deep sclerectomy, IOP remained below 10 mm Hg. During this period, mean IOP before each injection was 2.1±2.6 mm Hg, and each IVI caused a reduction of 1.2±0.8 mm Hg on average, with a maximum reduction of 2.7 mm Hg, before IOP normalized within 50 minutes to 24 hours. From 7 months postoperatively, mean IOP increased to the low teens. During this period, mean IOP before each injection was 9.9±1.8 mm Hg, and each IVI caused an increase of 15.8±11.7 mm Hg on average, with a maximum increase of 44.8 mm Hg, before IOP normalized within 20 minutes to 4 hours. Conclusions: During the initial postoperative phase, IVI may cause acute reduction in IOP, either through subconjunctival leaks or increased filtration secondary to increased fluid pressure. Several months after surgery, this effect subsides and IOP spikes sharply immediately after each IVI, suggesting the resolution of the initial mechanism, most likely through scarring and fibrosis.</p

The effect of daily life activities on intraocular pressure related variations in open-angle glaucoma.

The recent advent of continuous intraocular pressure (IOP) telemetry has led to an increased awareness of the importance of IOP fluctuations, and theories have emerged that IOP variations could play as much a role in glaucoma progression as the mean level of IOP. The aim of the present study was to evaluate the direct effect of common daily activities on IOP-related profiles. Primary open-angle glaucoma and glaucoma suspect patients were prospectively enrolled from specialist clinics at the University of California San Diego (UCSD), USA. Patients were fitted with a SENSIMED Triggerfish (TF) contact lens sensor (CLS) and were instructed to return to their usual daily activities for 24&nbsp;h. They were asked to record each specific activity or event in a diary. The protocol was repeated twice. The following events were recorded: "walking/cycling", "resistance training", "yoga/meditation", and "emotional stress". CLS measurements recorded 60-to-30&nbsp;min prior to each event were used as a baseline reference, and all IOP-related fluctuations for 120&nbsp;min after the start of each event were reported in relation to this reference. Forty relevant events from 22 CLS recordings in 14 patients were retrieved from the diaries. Walking/cycling (n = 10) caused a small but statistically significant elevation of the IOP-related profile during the activity (p = 0.018). Resistance training (n = 11) caused a persistent elevation of the IOP-related profile from the onset of the activity (p = 0.005) through 120&nbsp;min after the activity was stopped (p = 0.007). Yoga/meditation (n = 4) caused a sustained drop in the IOP-related profiles through to 120&nbsp;min, although this was not statistically significant (p &gt; 0.380). Emotional stress (n = 13) was associated with a gradual elevation of the IOP-related profile from the start of the stressful stimulus. Both early and late variations were statistically significant (p = 0.038 and p = 0.021, respectively). The present study suggests that emotional stress and resistance training may be associated with persistent IOP-related profile elevation

Delayed Obstruction of XEN Gel Stent by Cell Debris in Primary Open-angle Glaucoma: A New Insight into the Pathophysiology of Filtration Device Failure

Aim: The aim of this report is to explore the risk factors of XEN stent obstruction, suggesting the need for a stricter control of these factors and highlighting areas for further research. Background: Despite its proven effectiveness and safety profile, XEN gel stents (Allergan Plc, Dublin, Ireland) can become obstructed. The causes and predicting factors for such obstructions still require further research. While hyphema has long been known to be responsible for secondary glaucoma through trabecular obstruction, it has not been associated, to date, with XEN gel stent obstruction. Case description: We describe the case of a 55-year-old female patient with primary open-angle glaucoma (POAG) who underwent bilateral XEN gel surgery. Her left eye developed a 2 mm postoperative hyphema, which resolved spontaneously within 8 days. Intraocular pressure (IOP) normalized at 12 mm Hg and increased to 50 mm Hg after 1 month in an otherwise normal-looking eye. Intraoperative examination revealed a nonfunctioning XEN gel stent, which was replaced and sent for laboratory analysis. Macroscopic examination of the tube confirmed obstruction with cellular debris. Tube replacement restored good filtration. Conclusion: This case report confirms cellular debris as a potential cause of XEN gel stent occlusion, suggesting that aqueous red blood cells (RBCs) could potentially pose a threat to the microstents' patency even in cases when the bleeding was minimal and self-limited and where the IOP was still controlled at the time of full hyphema resolution. This observation could lead to recommendations for a stricter control of bleeding risk factors prior to microinvasive glaucoma surgery (MIGS), and it raises the question of whether anterior chamber (AC) washout should be advised in postoperative hyphema. Clinical significance: This case highlights some previously unreported risk factors for XEN stent obstruction and suggests that stricter control of bleeding and monitoring of patients following hyphema could improve surgical outcome

The effect of daily life activities on intraocular pressure related variations in open-angle glaucoma.

The recent advent of continuous intraocular pressure (IOP) telemetry has led to an increased awareness of the importance of IOP fluctuations, and theories have emerged that IOP variations could play as much a role in glaucoma progression as the mean level of IOP. The aim of the present study was to evaluate the direct effect of common daily activities on IOP-related profiles. Primary open-angle glaucoma and glaucoma suspect patients were prospectively enrolled from specialist clinics at the University of California San Diego (UCSD), USA. Patients were fitted with a SENSIMED Triggerfish (TF) contact lens sensor (CLS) and were instructed to return to their usual daily activities for 24&nbsp;h. They were asked to record each specific activity or event in a diary. The protocol was repeated twice. The following events were recorded: "walking/cycling", "resistance training", "yoga/meditation", and "emotional stress". CLS measurements recorded 60-to-30&nbsp;min prior to each event were used as a baseline reference, and all IOP-related fluctuations for 120&nbsp;min after the start of each event were reported in relation to this reference. Forty relevant events from 22 CLS recordings in 14 patients were retrieved from the diaries. Walking/cycling (n = 10) caused a small but statistically significant elevation of the IOP-related profile during the activity (p = 0.018). Resistance training (n = 11) caused a persistent elevation of the IOP-related profile from the onset of the activity (p = 0.005) through 120&nbsp;min after the activity was stopped (p = 0.007). Yoga/meditation (n = 4) caused a sustained drop in the IOP-related profiles through to 120&nbsp;min, although this was not statistically significant (p &gt; 0.380). Emotional stress (n = 13) was associated with a gradual elevation of the IOP-related profile from the start of the stressful stimulus. Both early and late variations were statistically significant (p = 0.038 and p = 0.021, respectively). The present study suggests that emotional stress and resistance training may be associated with persistent IOP-related profile elevation

A Metric to Consider on the Global Accessibility of Glaucoma Surgery

Comment on: Zhao PY, Rahmathullah R, Stagg BC, Almobarak F, Edward DP, Robin AL, SteinJD. A worldwide price comparison of glaucoma medications, lasertrabeculoplasty, and trabeculectomy surgery.JAMA Ophthalmol. 2018;136(11):1271-1279. doi:10.1001/jamaophthalmol.2018.367