Ophthalmology and Therapy最新文献

Introduction: This study investigates the early temporal changes in pigment epithelial detachment (PED) morphology following treatment with faricimab in patients with neovascular age-related macular degeneration (nAMD). Utilizing an artificial intelligence (AI)-assisted approach, we provide a detailed quantification and characterization of the dynamics of these morphological changes.

Methods: A prospective observational study was conducted on 22 eyes from 22 treatment-naïve patients with nAMD-associated PED (presenting either type 1 or type 3 macular neovascularization). Participants were administered intravitreal faricimab (6 mg) at baseline and at days 30, 60, and 90. Comprehensive ophthalmic evaluations and spectral-domain optical coherence tomography (SD-OCT) imaging were conducted at baseline and at seven additional follow-up visits on days 1, 7, 14, 30, 60, 90, and 120. An AI-based automated segmentation algorithm was utilized to precisely quantify changes in PED volume, alongside intraretinal (IRF) and subretinal fluid (SRF) volumes, at each time point.

Results: Treatment with faricimab resulted in a significant reduction in mean PED volume, with an average decrease of 12% at day 1, 29% at day 7, 51% at day 14, 68% at day 30, 72% at day 60, 79% at day 90, and 84% at day 120 (p < 0.0001 for all time points). Similarly rapid and marked reductions were noted in both mean IRF (23.5% at day 1, 90.7% at day 14) and SRF (14.4% at day 1, 91.2% at day 14) volumes. The study also showed a statistically significant improvement in best-corrected visual acuity (BCVA) over the follow-up period, correlating with the reduction in PED volume.

Conclusion: Faricimab demonstrates early and significant efficacy in improving PED architecture in patients with nAMD. The rapid morphological improvements observed in this study suggest faricimab may represent a valid therapeutic option for PEDs associated with nAMD.

Introduction: The purpose of this study is to identify the factors affecting neovascular age-related macular degeneration (nAMD) disease stability after brolucizumab treatment.

Methods: We retrospectively analyzed the medical records of 31 patients (31 eyes) with recalcitrant nAMD who were switched to brolucizumab after conventional anti-vascular endothelial growth factor (VEGF) treatment. We divided patients into two groups by treatment extension (TE) period: group 1 with TE < 12 weeks (N = 16) and group 2 with TE ≥ 12 weeks (N = 15). We compared outcomes between the groups at 2, 4, 8, and 12 weeks, including morphological characteristics of choroidal neovascularization (CNV). Logistic regression analysis identified factors associated with TE ≥ 12 weeks.

Results: Group 2 had a significantly greater proportion of patients with dry macula (subretinal and intraretinal fluids absent) than group 1 (60 vs. 12.5%) at 2 weeks (P < 0.05). Best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (SFCT) did not differ significantly between groups at all timepoints. Central subfield retinal thickness (CST) was significantly lower in group 2 at 2 (237.1 vs. 280.8 μm; P < 0.05), 4 (224.0 vs. 262.9 μm; P < 0.05), and 8 weeks (216.8 vs. 331.1 μm; P < 0.05). Group 2 had less vessel area (0.63 vs. 1.27 mm²; P < 0.05) and total vessel length (0.22 vs. 0.42 mm; P < 0.05). Choriocapillaris flow deficit (CCFd) was significantly lower in group 2 (42.7 vs. 48.2%; P < 0.05). Dry macula at 2 weeks (odds ratio [OR] = 8.3; P < 0.05) and a lower CCFd (OR = 0.73; P < 0.05) were associated with TE ≥ 12 weeks.

Conclusions: Early fluid-free status after switching to brolucizumab and choriocapillary function around CNV were prognostic factors for disease stability in nAMD refractory to anti-VEGF treatment.

Introduction: Dry eye disease (DED) is one of the most prevalent eye conditions worldwide, with artificial tears serving as a primary treatment option. Despite their wide availability on the European market, there is a lack of established classifications based on their physicochemical properties. The aim of our study was therefore (i) to develop an analytical method that measures the concentration and the molecular weight (MW) of the hyaluronic acid (HA) in commercialized products, and (ii) to propose an overview based on their various physicochemical parameters.

Methods: The intrinsic viscosity and MW of the HA, as well as osmolarity, pH, rheological profile, and viscosity, were measured or determined. A specific method was developed to measure the average intrinsic viscosity and HA content using a liquid size-exclusion chromatography system. The MW was determined using the Mark-Houwink equation.

Results: Thirty-seven products commercialized in Europe were analyzed, with 21 of them containing HA. The HA MW was lowest (300 kDa) for Thealose^®, Thealoz Duo^® Gel, and Hyabak^®, and highest (1300 kDa) for Vismed^® Multi, Vismed^® Gel, and Neovis^® Gel. The pH values varied between 5.94 for Treovis^® and 8.06 for Systane^® Ultra. Osmolarity ranged between 148 mOsm/L and 325 mOsm/L for Neovis^® and Treovis^®, respectively. Viscosity was highly variable, ranging from 0.38 mPas·s for Hylolipid^® to 337.47 mPas·s for Thealoz^® Duo Gel. Finally, rheological profile analysis revealed different shear-thinning behaviors.

Conclusion: While the perfect eye drop does not exist, a multitude of options are available to choose from. This study improves our understanding of the major tear substitutes available on the European market based on several physicochemical properties. A better understanding and awareness of these parameters is crucial in order to offer the best treatment for patients with DED.

Introduction: To evaluate the long-term effects of intense pulsed light (IPL) therapy on patients with dry eye disease (DED) associated with meibomian gland dysfunction (MGD).

Methods: A retrospective case series was performed with 110 participants undergoing IPL therapy. Assessments included the eye fitness test (EFT) to gauge subjective symptoms, along with objective measures using the Tearcheck^® device (ESW Vision, Houdan, France) noninvasive first breakup time (NIFBUT), noninvasive average breakup time (NIABUT), central tear meniscus height (CTMH), thinnest tear meniscus height (TTMH), and ocular surface inflammatory risk evaluation (OSIE) assessed using the SCHWIND SIRIUS device (SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany).

Results: This study documented significant improvements in subjective and objective symptoms associated with DED and MGD. Subjective symptoms measured by the EFT showed an average increase of 9.74 points (range -10 to 28, standard deviation [SD] ± 7.54), indicating reduced symptoms. Objective measures of tear film stability, represented by NIABUT, increased by an average of 4.04 s (range -15.00 to 14.40, SD ± 4.91). Tear film stability evaluation (TFSE) scores decreased by 229.12 points on average (range -1775 to 528, SD ± 384.94), suggesting enhanced tear film stability. OSIE type 1 showed a reduction in inflammation, with a percentage decrease of 4.98% (range -45 to 5, SD ± 7.33). Additionally, OSIE capture time decreased by 3.25 s on average (range -27 to 22, SD ± 10.35), further indicating an improvement in ocular surface health.

Conclusion: IPL therapy was shown to be a promising, noninvasive approach for improving quality of life in patients with DED by effectively managing symptoms and stabilizing tear film. The findings support the use of IPL as a sustainable treatment modality for DED associated with MGD.

Introduction: This study aims to evaluate the long-term clinical outcomes of excisional goniotomy with the Kahook Dual Blade (KDB) in the management of various types of glaucoma.

Methods: This was a retrospective, noncomparative chart review of 90 eyes of 53 patients with glaucoma that underwent standalone KDB goniotomy (KDB-alone group) or KDB goniotomy with concomitant phacoemulsification (KDB-phaco group) between October 2015 and October 2017. Surgical success was defined as an intraocular pressure (IOP) reduction by ≥ 20% at the last follow-up with no surgical reinterventions required and a final IOP ≥ 4 mmHg and ≤ 21 mmHg. We also report on changes from baseline in IOP, number of glaucoma medications, best-corrected visual acuity (BCVA), and visual field parameters, for up to 72 months.

Results: At 72 months, mean (standard deviation [SD]) IOP was reduced from 17.5 (5.7) to 13.6 (3.0) mmHg (P < 0.0001) in the KDB-phaco group and from 23.3 (5.9) to 15.1 (6.2) mmHg (P = 0.0593) in the KDB-alone group. The mean (SD) number of glaucoma medications was reduced from 1.3 (1.0) to 0.8 (0.9) (P < 0.0001) in the KDB-phaco group and from 1.2 (1.0) to 0.7 (0.8) (P = 0.3409) in the KDB-alone group. During the 72-month follow-up, surgical success was achieved in 24 of the 52 available eyes (46.2%). Four eyes underwent a glaucoma surgical reintervention by 72 months.

Conclusions: Excisional goniotomy with the KDB effectively lowered the IOP (by an average of 28.0% from baseline) and maintained or further reduced glaucoma medication burdens (by an average of 30.8% from baseline) under an excellent safety profile, independent of phacoemulsification status. The procedure exhibited favorable success for up to 6 years, providing valuable insights into its long-term efficacy as a glaucoma treatment.

Introduction: The aim of this study was to evaluate the efficacy and safety of escalating the dosage of intravitreal brolucizumab in patients with refractory neovascular age-related macular degeneration (AMD).

Methods: This retrospective study included 17 eyes of 17 patients with refractory AMD treated with high-dose brolucizumab (12 mg/0.1 ml) for over 12 months. Patients initially received at least one anti-vascular endothelial growth factor (anti-VEGF) agent and were switched to standard-dose brolucizumab (6 mg/0.05 ml). Those who showed a suboptimal response to standard-dose treatment had their dosage of brolucizumab escalated.

Results: Visual acuity was maintained from 68.3 ± 3.4 letters to 70.7 ± 3.2 letters after 12 months of high-dose treatment (P = 0.128). Central subfield thickness was 343.7 ± 17.0 μm before high-dose treatment and 316.7 ± 18.5 μm at 12 months (P = 0.083). The proportions of patients with subretinal fluid and serous pigment epithelial detachment significantly decreased from 82.4% to 41.2% and from 52.9% to 17.6%, respectively, after high-dose treatment (P = 0.039 and P = 0.031, respectively). The treatment interval extended from 7.2 ± 2.4 weeks to 10.2 ± 2.2 weeks after switching to standard-dose brolucizumab (P < 0.001) and was maintained at 13.5 ± 2.8 weeks after increasing the dose (P = 0.154). No severe ocular adverse events were observed.

Conclusions: High-dose brolucizumab was effective in patients who did not respond to standard-dose brolucizumab after switching from previous anti-VEGF agents. Increasing the dosage could offer sustained disease control and reduce the treatment burden for patients with refractory AMD.

Introduction: Cost-effectiveness analyses typically ignore healthcare system resource constraints. Ophthalmology is affected by resource constraints because of increasing disease prevalence and the use of resource-intensive treatments. This study evaluated the impact of resource constraints on the cost-effectiveness of faricimab 6 mg, compared with aflibercept 2 mg and ranibizumab biosimilar 0.5 mg, for treating wet age-related macular degeneration (wAMD) or diabetic macular oedema (DMO) over a 5-year horizon.

Methods: A microsimulation model estimated the impact of resource constraints on patients visits, delays, costs and quality-adjusted life-year (QALY) losses due to treatment delays at a typical UK National Health Service eye hospital treating 1500 patients with wAMD and 500 patients with DMO. Patient characteristics, treatment regimens and treatment intervals were informed using published literature and expert opinion. Resource constraint was represented by limiting the number of available intravitreal injection appointments per week, with growing demand caused by rising disease prevalence. The model compared outcomes across three scenarios; each scenario involved treating all patients with one of the three treatments.

Results: Over 5 years, in a resource-constrained hospital, compared with aflibercept, faricimab use resulted in the avoidance of 12,596 delays, saved GBP/£15,108,609 in cost and avoided the loss of 60.06 QALYs. Compared with ranibizumab biosimilar, faricimab use resulted in the avoidance of 18,910 delays, incurred £2,069,088 extra cost and avoided the loss of 105.70 QALYs, resulting in an incremental cost-effectiveness ratio of £19,574/QALY.

Conclusions: Accounting for resource constraints in health economic evaluation is crucial. Emerging therapies that are more durable and require less frequent clinic visits can reduce treatment delays, leading to improved QALY outcomes and reduced burden on healthcare systems. Faricimab reduced the number of delayed injections, leading to improved QALY outcomes for patients in a healthcare system with resource constraints. Faricimab is cost-saving when compared with aflibercept and cost-effective when compared with ranibizumab biosimilar.

Introduction: Patients with dry eye disease (DED) complain of a multitude of symptoms that affect their visual function and quality of life (QoL). This clinical investigation assessed the performance, tolerance, and safety of a novel preservative-free ophthalmic solution containing xanthan gum 0.2% and desonide sodium phosphate 0.025%.

Methods: This was an observational, prospective, multicentric, and post-market clinical investigation to assess the effect of three times a day instillation of the study formulation in patients suffering from DED. The primary objective was to achieve a 50% reduction in conjunctival hyperemia index as assessed with the OCULUS Keratograph after 1 month of treatment compared to baseline values. The secondary objectives included patient-reported outcomes, clinical performance, and safety.

Results: Thirty patients were enrolled (21 women, 9 men) with a mean age of 61.10 ± 14.53 years. The instillation of the study formulation was associated with a significant reduction in redness scores after 1 month of treatment compared to baseline (mean - 0.51 ± 0.51; p ≤ 0.0001). Although the primary endpoint was not completely met, a 50% reduction in the conjunctival hyperemia index was achieved in 23% of the participants, and 77% showed a reduction of 26% of the same index. In addition, the ophthalmic solution significantly increased tear film break-up time, and a significant reduction of corneal and conjunctival staining with fluorescein was achieved. It also reduced DED symptoms and had a very good safety profile.

Conclusions: the study formulation produced a significant improvement in the signs, symptoms, and QoL of patients with mild to moderate DED with a good safety profile after 1 month of treatment.

Introduction: OpenAI recently introduced the ability to create custom generative pre-trained transformers (cGPTs) using text-based instruction and/or external documents using retrieval-augmented generation (RAG) architecture without coding knowledge. This study aimed to analyze the features of ophthalmology-related cGPTs and explore their potential utilities.

Methods: Data collection took place on January 20 and 21, 2024, and custom GPTs were found by entering ophthalmology keywords into the "Explore GPTS" section of the website. General and specific features of cGPTs were recorded, such as knowledge other than GPT-4 training data. The instruction and description sections were analyzed for compatibility using the Likert scale. We analyzed two custom GPTs with the highest Likert score in detail. We attempted to create a convincingly presented yet potentially harmful cGPT to test safety features.

Results: We analyzed 22 ophthalmic cGPTs, of which 55% were for general use and the most common subspecialty was glaucoma (18%). Over half (55%) contained knowledge other than GPT-4 training data. The representation of the instructions through the description was between "Moderately representative" and "Very representative" with a median Likert score of 3.5 (IQR 3.0-4.0). The instruction word count was significantly associated with Likert scores (P = 0.03). Tested cGPTs demonstrated potential for specific conversational tone, information, retrieval and combining knowledge from an uploaded source. With these safety settings, creating a malicious GPT was possible.

Conclusions: This is the first study to our knowledge to examine the GPT store for a medical field. Our findings suggest that these cGPTs can be immediately implemented in practice and may offer more targeted and effective solutions compared to the standard GPT-4. However, further research is necessary to evaluate their capabilities and limitations comprehensively. The safety features currently appear to be rather limited. It may be helpful for the user to review the instruction section before using a cGPT.

Introduction

This work aims to determine the effect on nerve fiber layer (NFL) and ganglion cell complex (GCC) thickness trends in eyes with open-angle glaucoma (OAG) treated with Vision Protection Therapy™ (VPT).

Methods

A retrospective analysis of spectral-domain optical coherence tomography (OCT) measured NFL and GCC thickness trends was performed, excluding eyes with poor-quality scans and principal diagnoses other than OAG. This study compares eyes with OAG managed conventionally with IOP control alone (controls) to eyes managed with the addition of VPT (VPT eyes). The direction (+ or −) and magnitude (microns/year) of the OCT trends were the study endpoints.

Results

Seventy-eight control eyes of 40 patients and 61 VPT-treated eyes of 39 patients were included in the study. Positive NFL trends were noted in 5% of control eyes vs. 71% of VPT eyes (p < 0.0001). Positive GCC trends were noted in 8% of control eyes vs. 43% of VPT eyes (p < 0.0001). Mean NFL trends (µm/year) were − 0.692 for controls vs. 0.347 for VPT (p < 0.0001). Mean GCC trends (µm/year) were − 0.554 for controls vs. − 0.148 for VPT (p = 0.0175).

Conclusions

The addition of VPT to the conventional management of OAG resulted in highly significant improvements in NFL and GCC trends, indicating a reversal of key indicators of glaucoma severity and progression.